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CAPG Consulting Report: The New In-Home Care, p.12 & 14

Physician Compensation: Four Keys to Success, p.22

Using Technology to Deliver ‘High-Touch’ Patient Care, p.44

healthVolume 11 • No. 3 COllOQUIUM ISSUe Fall 2017

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Home Is Best, Where Cost Is Less

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ON the COVer 12 & 14caPG consulting Report: the new In-Home careTwo CAPG Consultants share the latest trends, challenges, and best practices in value-based home health.

DepartMeNtS

6From the president

8Names in the News

Upcoming events

policy Briefing

Oregon’s Coordinated Care Organizations:

Not Your average aCOs

Federal policy Update

Is a Win for the Value Movement

on the horizon?

22CapG Member Spotlight

pearls of physician

Compensation

26CapG Member list

FeatUreS

24physicians Can Be at risk When

homebound patients refuse help

40a New Model of home-Based Care

42home-Based Care: Operational pearls From

an Integrated Care Organization

44Using technology to Make healthcare

Delivery More patient-Centric

healthPublisherValerie Okunami

Editor-in-ChiefDon Crane

Editorial Advisory Board Lura Hawkins, MBA Amy Nguyen Howell, MD, MBA Mary Kay Payne, Arch Health Partners

Managing EditorDaryn Kobata

Editorial AssistantNelson Maldonado

Contributing WritersBill BarcellonaRuth Benton Matt CouryDon CraneMariella CummingsCraig DePriester Robin Diamond Lisa Humphreys, MD Amy Nguyen Howell, MDDawn MaroneyMargaret PetersonJeremy Rich, DPMNeil Solomon, MDBart Wald, MD, MBAJorge Weingarten, MD

CAPG Health Magazine is published byValerie Okunami MediaPO Box 674, Sloughhouse, CA 95683Phone 916.761.1853

capghealth.comPlease send press releases and editorial inquiries to [email protected] or c/o CAPG Health, 915 Wilshire Blvd., Suite 1620, Los Angeles, CA 90017

For advertising, please send email to [email protected]

Subscription rates: $32 per year; $58 two years; $3 single copy.

Advertising rates on request. Bulk third class mail paid in Jefferson City, MOEvery precaution is taken to ensure the accuracy of the articles published in CAPG Health Magazine.

Opinions expressed or facts supplied by its authors are not the responsibility of CAPG Health Magazine.

© 2017, CAPG Health Magazine.All rights reserved.

Reproduction in whole or in part without written permission is strictly prohibited.

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From the presidenta MeSSaGe FrOM DONalD CraNe, preSIDeNt aND CeO, CapG

Donald Crane, CAPG President and CEO

CapG members and friends,

Welcome to the Colloquium edition of CapG health, focusing on homebound health—an important component of value-based, patient-centered care. Our cover features the CapG Consulting team: highly experienced, recently retired former CeOs who stand ready to share their insights for success in risk-based delivery. Several Consultants will be at the CapG Colloquium, and I hope you have a chance to meet them.

the Colloquium 2017 theme is healthcare reform: the Saga Continues. amid the uncertainty over the affordable Care act’s fate, it’s more vital than ever to continue advancing value-based delivery—which many on both sides agree is a proven solution for improving quality and cutting costs.

One area of CapG’s value advocacy where we’ve seen concrete progress is Medicare advantage (Ma). CapG continues to be the leading physician voice on Ma issues. In particular, since passage of the Medicare access and ChIp reauthorization act (MaCra) in 2015, we’ve called for risk-bearing Ma arrangements to be given equal footing with alternative payment models in traditional Medicare under MaCra.

We’re pleased with the progress made on this issue, and we continue to need your support to advance the cause. this year, CapG has attended several meetings with CMS and the White house, urging that Ma risk contracts be counted as advanced apMs. We’ve assembled a strong national coalition of supporters on this issue, including health industry stakeholders and physician organizations. this effort has included numerous stakeholder meetings, sign-on letters, and outreach to members of Congress and the administration.

Most recently, in response to CMS’s proposed MaCra rule for 2018, CapG submitted a detailed proposal outlining a demonstration project that would enable physicians and physician groups in Ma to qualify as advanced apMs and receive the 5 percent apM bonus. We know that Medicare advantage apMs hold great potential. earlier this year, research showed that patients treated by physician organizations that are capitated downstream experienced higher quality care and longer survival than those in fee-for-service downstream. Ma’s superiority for patients is the main reason CapG remains a committed advocate for the model.

We expect to see additional guidance on this topic from CMS later this fall. We hope to see you at the Colloquium, where you’ll hear updates on this and other pressing issues. o

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WelCOMe tO OUr NeWeSt MeMBerS

CapG warmly welcomes these members who have recently joined:

Organizational MembersIn Salud, Guaynabo, puerto ricophM MultiSalud, llC, San Juan, puerto ricoreliant Medical Group, Worcester, Maarizona health advantage, Inc., Chandler, aZhealthCare partners, Ipa, Garden City, NYUC Davis health, Sacramento, CaDFW healthCare partners, llC, plano, tXpeoples health Network, Metairie, laMartin luther King, Jr. Community Medical

Group, los angeles, Ca

CathOlIC health INItIatIVeS reCeIVeS $2.5 MIllION GraNt FOr tOtal health rOaDMap

Catholic health Initiatives (ChI) has been awarded a $2.5 million grant from the robert Wood Johnson Foundation. the grant will help ChI implement its total health roadmap, an innovative model to address social determinants of health as an integral part of healthcare and to develop pathways and opportunities to build and sustain healthy communities.

“Considering the social determinants of health will be a standard of care in primary care practices in each of the three pilot markets, which will actively recruit and lead community partners in identifying and addressing the most important needs and issues facing their communities,” says Kevin e. lofton, CeO of Catholic health Initiatives.

the nation’s third-largest nonprofit health system, ChI is matching the grant with a $2.5 million award from its Mission and Ministry Fund. It has launched total health roadmap in three of its largest markets: Denver-based Centura health; KentuckyOne health, based in louisville; and Mercy health Network, headquartered in Des Moines, Iowa.

Names in the NewsMethODISt le BONheUr healthCare NaMeD a Great WOrKplaCe FOr WOMeN

Methodist le Bonheur healthcare, an integrated healthcare delivery system based in Memphis, tennessee, has once again been named to the Fortune list of “Great places to Work for Women.” the organization was ranked at No. 11, moving up from No. 18 last year.

Fortune creates the national list based on several factors, including a survey of over 400,000 US employees. In that survey, women rate their organizations on more than 50 measures, including ethical leadership, respectful and fair workplace interactions, development opportunities, and more.

“providing a desirable culture and a great place to work impacts all of our associates,” says Carol ross-Spang, Chief human resources Officer for Methodist le Bonheur healthcare. “By focusing on engagement and retention, we improve our patient experience and quality outcomes. Our strong power of One Culture supports our associates in bringing their ‘a’ game to work every day, thereby ensuring that our patients and families get the best possible care.”

CeDarS-SINaI appOINtS NeW VICe DeaN OF reSearCh aND eDUCatION

ravi thadhani, MD, Mph, a world-renowned nephrology expert, has joined Cedars-Sinai as Vice Dean of research and education. a prominent investigator, scholar educator, and clinician, thadhani comes to Cedars-Sinai from Boston, where he was a professor of Medicine at harvard Medical School, Chief of the Division of Nephrology at Massachusetts General hospital, and executive Director of the Clinical trials Office at partners healthcare.

thadhani has demonstrated remarkable scholarly creativity, coupled with outstanding mentoring of trainees and junior faculty. he is an internationally renowned clinical and translational leader in nephrology, heading a highly productive research laboratory at Massachusetts General hospital, with more than 250 publications in the New england Journal of Medicine, the Journal of the american Medical association, the lancet, and other top-tier scientific journals. o


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scaPG colloquIum 2017Wednesday-Friday, November 8-10Washington, hyatt regency on Capitol hillcapgcolloquium.com

caPG educatIonal seRIes WebInaRs WItH cmsFriday, December 1capg.org/qpp

state GoveRnment PRoGRams commItteetuesday, November 14 CapG

soutHWest ReGIonal meetInGtuesday, November 28phoenix, location tBD

state PolIcy commItteethursday, November 30Webex

texas ReGIonal meetInGthursday, December 7houston, location tBD

fedeRal PolIcy commItteethursday, December 14Webex

Save the Dates2018 CAPG Annual ConferenceApril 19-21, 2018Manchester Grand HyattSan Diego, CA

2018 CAPG ColloquiumOctober 10-12, 2018Hyatt Regency on Capitol HillWashington, DC


Fall 2016 capg health l 11

2018 Media Kit

CelebRATinG

10 yeARS SuPPORTinG THe MeSSAGe & MiSSiOn Of CAPG THROuGHOuT AMeRiCA

Reach influential leaders in the healthcare value movement in 2018 with new features:

• Regional editions within the magazine highlighting current feature stories on critical topics in the Western, Midwestern and eastern Regions of America

• 50% increase in hard copy distribution to specific regions

• Advertisers choose to market their products and services in specific regions or the entire nation

AnnuAl COnTRACTS — CAPG MeMbeRS ReCeive SPeCiAl DiSCOunTS

for editorial guidelines, visit capg.org/editorial or email valerie Okunami at [email protected].

for media kit and marketing questions, email valerie Okunami at [email protected].

2 0 1 8 C a l e n d a rSpring 2018 Taking Responsibility for America’s Health

Regional Focus: Northwest (Washington & Oregon)

Editorial and advertising dueFriday, December 1, 2017

SUMMEr 2018CApg Annual Conference issue 2018

American Healthcare 2018: Coordinated Care Adapts

Regional Focus: Texas

Editorial and advertising due Friday, February 16, 2018

FAll 2018 CApg Colloquium issue

Healthcare Forecast/Election Year

Regional Focus: Northeast/Mid-Atlantic

Editorial and advertising due Friday, July 27, 2018

top employers: 25%

healthcare Industry: 70%

policymakers 5%

70%

5%

25%


Medical groups and independent practice associations (Ipas) are increasingly incorporating home care services as they contract under value-based alternative payments. Groups and Ipas committed to coordinated care are developing new models for home care to respond to the needs of various managed care populations, consistent with benefit design features and payer agreements. this work is driven by the demographic growth of the senior population, as well as incentives from the Medicare access and ChIp reauthorization act (MaCra).

Medicare and Medicaid fund the majority of home care services. patients in Medicare advantage and traditional Medicare, as well as dual-eligible beneficiaries, are the most likely to benefit from this care.

home care models have been shown to improve quality and reduce costs. Five models were recently evaluated by ruiz et al, confirming that each model improved at least two—and as many as four—quality measures. Four of the five models studied also demonstrated reductions in costs, hospitalizations, or emergency department use, compared with controls.1 a comparative analysis by Mattke et al reported similar results within a Medicare advantage population.2 the 2017 Institute for healthcare Improvement/National patient Safety Foundation monograph, “patient Safety in the home,” provides a comprehensive discussion of model options, resources, and challenges.3

TRenDS in MeDiCARe HOMe CARe

to be eligible for home care services under Medicare, a beneficiary’s physician must certify that the patient meets the definition of homebound. In addition, home care must be consistent with a plan of care verified by a face-to-face clinician encounter prior to or within 30 days of initiation of services, and services are limited to skilled nursing and rehabilitation therapies. Only a certified home health agency (hha) can provide this care. the Medicare home health benefit excludes 24-hour home care, prescription drugs, meals, and homemaker or custodial care services. however, some of these services may be available under the separate Medicare hospice benefit.

In 2000, reimbursement to hhas shifted from fee-for-service (FFS) to prospective payment. In its March 2017 report to Congress,4 the Medicare payment advisory Commission (Medpac) reported that there was a 66 percent increase in the number of certified hha providers between 2000 and 2014. as of 2015, 3.5 million beneficiaries were using home health (9.1 percent of FFS beneficiaries overall), averaging 33 visits per user and costing $18.1 billion.

on the cover

incorporating Home Care in value-based ContractingBY MarIella CUMMINGS, CapG CONSUltaNt

“pCp coordination is a critical success factor, together with timely documentation of visit activities to the pCp office and others involved in patient care.”

In this report, CAPG Consultants Mariella Cummings and Dr. Bart Wald (page 14) study aspects of home care, a critical component in value-based delivery. Learn more about CAPG Consulting, a group of highly experienced accountable care executives, at capg.org/consulting.


Medpac determined that there is adequate geographic access to home health—with 99 percent of beneficiaries residing in a county with at least one hha, and 86 percent having access to as many as five certified agencies.

however, regional staffing shortages may limit access to hha services.5 For example, physicians of Southwest Washington (pSW), an Olympia-based Ipa and a majority owner in Northwest Momentum health partners, a Next Generation aCO, reports delays in hha patient evaluations due to staffing.6 Other approaches may be necessary to provide prioritized, coordinated, and timely home-based services, even within a traditional Medicare population.

TARGeTeD HOMe viSiTS

home visits can address the needs of patients who:

• have significant and sub-optimally controlled chronic conditions (to supplement telephone outreach and telemetric monitoring)

• are transitioning from hospital or sub-acute care to home

• have co-morbid behavioral and physical problems, including dementia

• Demonstrate inappropriate utilization patterns, such as excessive emergency department visits, which may be the result of inadequate patient/caregiver education or challenges related to social determinants of health

• have not had an annual wellness visit

the focus of each home visit determines the appropriate staffing by license and skill. rarely will it be practical or cost-effective for a primary care physician (pCp) to do a home visit. however, pCp coordination is a critical success factor, together with timely documentation of visit activities to the pCp office and others involved in patient care. Coordination and information-sharing with acute care and skilled nursing facility (SNF) discharge planning staff, as well as community-based organizations that may be providing complimentary services, is essential to avoid duplicating efforts.

Medical groups and Ipas have implemented many successful home care approaches, including:

• expanding the role of care management staff to include both telephonic and in-person visits as part of comprehensive acute and chronic care management systems.

• Contracting for annual wellness visits and follow-up on chronic conditions.

• Contracting with licensed providers to visit discharged patients within 24 hours to confirm stable medical status and compliance with discharge instructions. (Medication reconciliation and compliance is often a key to averting er visits and hospital readmissions.)

• Creating systems for prompt pCp follow-up communication about identified patient problems. these are essential to optimizing the clinical value of all home visits.

ReiMbuRSeMenT fOR HOMe viSiTS

transitional Care Management (tCM) is an evolving new benefit under Medicare that includes reimbursement for services upon discharge from acute and sub-acute settings. Only one provider can bill for such services, which must be implemented within 48 hours of discharge. there must be either an in-person home or office visit within seven to 14 days of discharge, and there are many requirements for care coordination. reimbursement for tCM is higher than standard home visit rates.7

Below are some Medicare tCM reimbursement examples:

• tcm visit: either $165 or $234, depending on how soon the in-person visit occurs and the degree of medical decision-making required during the 30-day tCM service period.

• Physician home visits: $56–$224 for new patients, and $56–$181 for established patients.

• HHas that submit quality data: $2,990 per 60-day episode. low utilization individual payments vary by type of provider, between $64 and $227. prudently implemented home care can play a significant role in reducing total cost of care.

It is possible for a physician practice or its Ipa to subcontract with an outside vendor for tCM and other home visit activities, with the contracting practice billing the patient’s insurance for services.

SPeCiAl COnSiDeRATiOnS fOR iPAS

Unlike medical group organizational structures, Ipas that “facilitate or arrange for healthcare services”

continued on page 39


For too long, managed care organizations have been criticized for exerting more effort on “managing costs” than “managing care.” Most recently, there has been greater awareness that more intensive and focused care for high-risk and high-cost patients is critical to the success and evolution of risk-managing coordinated care organizations.

It is estimated that over two million seniors meet the traditional definition of homebound, and millions more have significant difficulties leaving home. this does not include many younger adults with crippling diseases and limited mobility. there is growing appreciation of the need to expand in-home care for patients who can’t or won’t obtain needed care in the office setting. this includes patients who can’t access transportation, have behavioral or mental illness problems, and/or may be homeless.

Unlike conventional “home health” provided by nurses and therapists, the new “in-home care” is managed by physicians and provided by physicians, nurse practitioners, dietitians, pharmacists, social workers, rehab, and mental health specialists. these in-home providers can also better assess environmental, family, and other social determinants of health.

providing in-home care is more inefficient and costly, and the costs and complexity can be intimidating. But it’s a third rail of healthcare—if you don’t try it, you won’t get your care engine to run with maximum effectiveness. If you approach it wrong, though, it can be a risky drain on limited resources.

Fortunately, a growing number of groups and vendors have been experimenting with in-home care long enough to learn and share some best practices. Below are four examples:

MOnARCH MeDiCAl GROuP

Monarch Medical Group is an Orange County, California-based physician group with over 250,000 lives under risk and clinical management. Monarch has stratified its in-home care programs into four segments:

1. the supportive care Program works with frail elderly patients—those who are not homebound but have significant functional limitations. these patients are identified primarily through claims data—showing evidence of oxygen therapy, wheelchairs, chronic diseases, and other predictors such as falls, fractures, sepsis, dementia—and a risk-scoring predictive model tool. these patients receive regular visits from rNs and nurse practitioners.

2. a High-Risk touch team provides a comprehensive post-hospital discharge visit by an rN, social worker, and/or pharmacist. patients are referred by their hospitalists, guided by their laCe score. this program was started because Monarch—like many other groups—found that few patients were willing or able to see their primary care physicians (pCps) shortly after discharge because they were still too weak, sick, or unable to access transportation.

3. the In-Home Palliative care Program is staffed by MDs, Nps, and rNs and provides 24/7 symptom management for patients identified as having a life expectancy of less than 12 months.

on the cover

in-Home Care: Reaching the unreachableBY Bart WalD, MD, MBa, CapG CONSUltaNt

“there is growing appreciation of the need to expand in-home care for patients who can’t or won’t obtain needed care in the office setting.”


4. comprehensive Homebound care is for true homebound patients. a contracted vendor provides “proxy pCp” care for these patients.

to help extend its program, Monarch has experimented with such technologies as remote monitoring. But it has found that seniors often can’t or won’t use these technologies on their own.

HOuSeCAll DOCTORS MeDiCAl GROuP (HDMG)

housecall Doctors Medical Group (hDMG) has been providing in-home care to seriously ill patients for almost 15 years. like many physicians engaged in this work, hDMG founder and Chief Medical Officer Norman Vinn, DO, has seen the need for these services during his group experience.

Currently, hDMG contracts to provide these services to over 2,500 patients for more than 10 groups. But Dr. Vinn believes that the value proposition is still not well understood, and the difficulty of identifying the true “high value” patient is a significant barrier.

Dr. Vinn believes the key to hDMG’s success is providing a customized interdisciplinary team that emphasizes the competencies and culture of his providers—as well as patient relationships that improve understanding and compliance with optimal treatment regimens.

MeDZeD

another entity contracting with payers to provide in-home care is MedZed. MedZed is also led by a seasoned managed care veteran, Neil Solomon, MD. It currently offers two programs: a 30-day focused post-discharge transition of care and a long-term in-home care program for high-risk and medically complex patients.

MedZed manages a sizable number of high-risk MediCal patients who suffer from chronic diseases, behavioral issues, and substance abuse. Its work necessarily focuses on social determinants of care, and it has introduced behavioral health providers to manage medications and to coach pCps on behavioral problems.

MedZed has made a major commitment to technology. Most of its clinician services are provided via a proprietary telemedicine platform brought into the home by a visiting nurse. as a result, its clinicians can double the number of patient encounters per day. MedZed uses plug-in stethoscopes and high-resolution cameras to expand the scope of its clinicians. the group also provides a 24-hour call center that responds to patient needs and contacts on-call clinicians when necessary. a logistics platform provides efficient scheduling of visits, and the group collects and analyzes data to continually improve its program.

Should groups and payers “make or buy” in-home care services? Dr. Solomon says the advantage of contracting is that groups get an advanced system to start with—rather than having to ramp up their learning—as well as scalability that offers more efficient coverage for patients who may be dispersed through the community.



Oregon’s Coordinated Care Organizations: Not Your average aCOs

BY BIll BarCellONa, SeNIOr Vp FOr GOVerNMeNt aFFaIrS, CapG

Oregon has pioneered several unique approaches to healthcare over the past few decades. One of the state’s most notable successes has been the creation of coordinated care organizations (CCOs). recently, I flew up to portland to meet with several people who formed and operate these CCOs. there are lessons to be learned from the path that Oregon has taken.

Coordinated care organizations were formed to implement Oregon’s vision of health system transformation. the guiding principle was that increased preventive healthcare would lower overall spending, improve population health status, and increase individual patient experience with wellness. In essence, Oregon walked the talk of the “triple aim.”

Sixteen CCOs were formed across the state. half are for-profit; half are not-for-profit. Most were formed out of existing regional managed care organizations (MCOs), and many of them are independent practice associations (Ipas). they are required to maintain a community-based governing board that includes risk-bearing entities, healthcare providers, community members, and other health system stakeholders.

the state statute requires that a CCO accept full-risk capitation. It must provide coverage and services for physical, behavioral, and oral health. It also must utilize community needs assessments under a strategic health delivery plan, use evidence-based practice standards, and incorporate health information technology throughout the delivery system. long-term supports and services and psychotropic medication costs are excluded from the global risk model.

leslie Clement, the Director of health policy and analytics for the Oregon health authority, states emphatically that CCOs differ from aCOs in that they engage patients directly in the spectrum of care and delivery of services. When initially created, CCOs attracted 40 percent of the Medicaid-eligible enrollees through a voluntary enrollment mechanism. today, 89 percent of the Medicaid population is enrolled in CCOs.

Oregon is the ninth largest state by geography but only the 27th largest by population (about 4.1 million lives). Most of the population is concentrated along the Willamette Valley corridor, situated west of the Cascade Mountains. about one in four Oregonians are covered under Medicaid.

the state has been undergoing steady economic and population growth, but there has been frustration over the inability of Oregon’s tax system to provide the right level of revenue in times of economic growth. Many feel that the legislature was overly optimistic when it opted for expansion under the affordable Care act, and while the economy has grown, the number of Medicaid-eligible individuals has grown as well. Oregon’s job market is strong: Wages are growing at 4 percent annually, and unemployment rates are lower than the national average. While the state planned for about 200,000 newly covered individuals, the actual enrollment topped 400,000 lives.

policy Briefing

“It is readily apparent that CCOs are having an impact on the health status of the entire community, not just the Medicaid-eligible.”


the Oregon legislature is facing a $1.6 billion budget shortfall for the next two-year budget cycle. Most of this amount, about $1 billion, is attributed to Medicaid funding, as federal Medicaid expansion funding drops from 100 percent to the FMap level. the initial phase of CCO deployment has produced a $1.4 billion savings in healthcare expenditures, and avoidable hospitalizations have decreased by a third since 2012. Oregon now spends about $438 per month on each Medicaid beneficiary.

CCOs will now move into a second phase under a new Centers for Medicare & Medicaid Services (CMS) Section 1115 wavier contract, which runs from 2017 to 2022. While Oregon sought increased funding from CMS, the waiver continues the CCO program—but without additional funding.

Oregon’s health system transformation has increased the development of patient-centered medical homes among smaller physician practices. Sixty percent of the CCO physician workforce is now certified under the Oregon medical home model. the patient-Centered primary Care home (pCpCh) program standards were developed through a public process in 2009 and adapted for CCOs in 2012.

at the time, the standards were more outcome-focused than the National Committee for Quality assurance (NCQa), but now both are very similar. there were three tiers of certification used by CCOs, commercial plans, and the public employees Benefit Board (peBB) system, and this has now been expanded to five tiers.

a recent study found that the proliferation of pCpCh sites reduced the total spend by $13 per member/per month across all participating payers. For every $1 increase in primary care spend in these practices, $13 in savings accrued in other services, such as specialty care, emergency department, and inpatient care. Overall, the pCpCh model saved $240 million over three years. New legislation will require that 12 percent of every premium dollar be spent on primary care for public and private health plans by 2023.

In the next phase, there will be a greater focus on rewarding primary care providers through value-based payment models. While CCOs are paid on a full-risk basis, we were told that there is still a high rate of fee-for-service payment downstream to providers. One CFO told us that physicians are paid better under Medicaid than in Medicare advantage. eighty-eight percent of Oregon’s doctors see Medicaid patients. at the CCO level, the state will focus on increasing the proportion of total payments based on performance over time, using a 17-metric outcome-driven standard.

the Oregon CCOs routinely gather to share best practices and brainstorm innovations. as I listened to several CCOs detail their successes and challenges during my weeklong trip, I was struck by the overwhelming commitment to the inclusion of social determinants of health in the delivery system strategy. there is a high level of enthusiasm for greater innovation and outreach to Medicaid customers, and it is readily apparent that CCOs are having an impact on the health status of the entire community, not just the Medicaid-eligible. there has been positive improvement in behavioral health integration through the community-oriented approach of the CCO model. Dental treatment has been successfully incorporated into the regional models as well.

In addition to the looming financial challenges at the state level that persist in any Medicaid program, I noted two big challenges on the minds of many of the people I spoke with.


It’s fall again in Washington, DC. Congress and the president have returned to the swamp to an incredibly long to-do list—and a very short timeframe in which to complete it. Fewer than 30 legislative days remain before the end of the year, and the political climate is more polarized than ever. On this list: tax reform (the vehicle for 2018 budget reconciliation), funding the government beyond December 8, and of course, the looming healthcare challenges facing our nation under a destabilized affordable Care act (aCa).

after the Senate failed to advance legislation to repeal and replace the aCa, efforts to move a large repeal-and-replace package have stalled. republicans are now eyeing early 2018 as the earliest opportunity to again attempt to repeal the aCa.

On October 12, the administration announced that it will no longer continue to make the cost-sharing reduction (CSr) payments to insurance companies, creating even greater instability in the aCa individual health insurance market. Senate committee leaders have been working on bipartisan legislation to provide two years of certainty for CSrs in exchange for increased state regulatory flexibility, but the specifics of the deal are still being hammered out. the CSr announcement—coupled with president trump’s executive order to modify some of the current restrictions created by the aCa and provide new insurance options—has only added to the confusion and instability in the healthcare system.

accordingly, it is no surprise that this year has largely been a distraction from the value movement. the wider political brouhaha and aCa debate have distracted lawmakers and regulators from focusing on year one of MaCra implementation and the new alternative payment pathways it created. however, a significant win for the value movement may be looming on the horizon: Medicare advantage alternative payment Models.

as background, the Medicare access and ChIp reauthorization act (MaCra) replaced the untenable sustainable growth rate (SGr) as the statute that governs provider reimbursements under the Medicare physician fee schedule. Under MaCra, there are two payment tracks: the Merit-based Incentive payment System (MIpS) and advanced alternative payment Models (apMs).

MaCra includes a 5 percent incentive payment for certain participants in advanced apMs. Qualifying apMs must meet statutory and regulatory criteria, and to date, they have only included models in traditional Medicare and not Medicare advantage (Ma) risk contracts. CapG is advocating for the inclusion of Ma risk contracts that meet the MaCra statutory criteria. this policy change would allow physicians and physician groups to qualify as advanced apMs (and receive the part B bonus) by taking risk in Ma.

CapG has long advocated for the integration of Ma into MaCra, including the advanced apM track, and our efforts in 2017 have finally yielded headway. In

BY MarGaret peterSON, D IreCtOr, FeDeral aFFaIrS , CapG

Federal policy UpdateIs a Win for the Value Movement on the horizon?


“We expect the MaCra final rule sometime late this fall, and we are optimistic that it may include a pathway for the inclusion of Medicare advantage in the advanced apM track.”


June, when addressing attendees of the CapG annual Conference in San Diego, California, then-health and human Services (hhS) Secretary tom price maintained that hhS and the Centers for Medicare & Medicaid Services (CMS) are in a “receiving mode,” and CapG has been broadcasting.

to encourage CMS to utilize its regulatory authority to include Medicare advantage in calculations toward participation in advanced apMs, CapG also met with CMS administrator Seema Verma as part of a broader MaCra strategy meeting. Verma and her staff indicated they are supportive of developing a pathway to achieve this goal.

earlier this year, CapG led a letter to CMS signed by nearly 300 physician groups and Ipas urging action on this issue. CapG also formed an industry coalition that petitioned the agency. the coalition included america’s health Insurance plans (ahIp), the health Care transformation task Force, the alliance of Community health plans, NCQa, and the National Coalition on

health Care, among others. Moreover, we leveraged our relationships in Congress to initiate a bipartisan sign-on letter in the house of representatives. the letter urged administrative action and was signed by 24 members of Congress.

this June, CMS released its proposed rule that would implement MaCra for the 2018 performance year. In the proposed rule, CMS requested information on how it can use its demonstration or waiver authority to count Ma risk contracts as advanced apM participation in 2018. this was a departure from prior rulemaking, where the agency had maintained it had no authority to act on Ma apMs—and represented a real win for both the value movement and Ma providers.

In subsequent conversations with CMS, agency representatives have asked for input on how to design such a demonstration. Notably, Demetrios Kouzoukas, principal Deputy administrator of CMS and Director of the Center for Medicare, asked CapG president and

continued on next page


CeO Don Crane to submit a demonstration design to the agency. CapG has responded with a detailed proposal, and we have received positive responses from both the administration and other stakeholders on our specific model. this fall, we met with staff at the Center for Medicare & Medicaid Innovation (CMMI) to walk through our proposed Ma apM demonstration project and the specifics of our model.

CapG will continue to meet with CMS and members of Congress to press forward on this issue. We expect the MaCra final rule sometime late this fall, and we are optimistic that it may include a pathway for the inclusion of Ma in the advanced apM track.

Congress designed MaCra to incent physician movement from the MIpS track to the advanced apM track. this latter track is where real innovation and progress away from traditional fee-for-service payment arrangements occur. With CMS first delaying, then proposing to cancel or reduce three mandatory bundled payment programs, it is more important than ever that new advanced apM models are approved.

If nothing replaces the mandatory bundles, and new and innovative models are not proposed in a timely manner,

it wastes the time and effort many forward-thinking organizations (including many CapG members) have already put into preparing for further value-based reimbursements. Many of these organizations have been successfully utilizing bundled payments and value-based models for years.

everyone agrees: the value movement is the future of healthcare in america. right now, healthcare costs are rising while the quality of healthcare isn’t improving. achieving a more value-based reimbursement system is the best way to align beneficiary, provider, and payer incentives and truly improve healthcare in our nation.

as CapG members know, downstream risk contracting in Medicare advantage is one of the most successful, high-quality, low-cost apMs available today. however, this model is not available across the country and is not eligible for MaCra incentive payments. With over one third of all Medicare beneficiaries enrolled in Ma, incorporating incentives for value-based contracting in Ma is essential to transforming the delivery system.

It is a mistake to ignore the untapped potential of Ma to truly move the value movement forward. Integrating Medicare advantage into the value movement is critical, and we are optimistic that our advocacy on this issue will lead CMS to do just that. o

WHOISMAZARS.COM

MAZARS USA IS HELPING ITS CLIENTS IMPROVE THE BUSINESS OF MANAGED CARE.

Mazars USA’s Health Care Group is proud to support CAPG and its mission to assist health plans and accountable physician groups to improve the quality and value of healthcare provided to patients.

We are experienced with Regulatory Audit Preparation, Organizational Assessments, Provider Directory & Access/Availability, Licensing & CCertification, Contract Management & Analysis, Mergers & Acquisitions and Compliance.

Find out how Mazars can help optimize your organization’s performance.

Gil Enos, [email protected]

continued from page 19

fordateTHE 2018

CONFERENCES

CAPG ANNUAL CONFERENCE 2018

Apr i l 19-21Manchester Grand Hyat t , San D iego, CA

CAPG COLLOQUIUM 2018

October 10-12Hyat t Regency on Cap i to l H i l l , Wash ington, DC

See you there!

CAPG ANNUAL CONFERENCE 2018

Apr i l 19-21Manchester Grand Hyat t , San D iego, CA

CAPG COLLOQUIUM 2018

October 10-12Hyat t Regency on Cap i to l H i l l , Wash ington, DC

See you there!


BY rUth BeNtON, CeO, NeW WeSt phYSICIaNS

Without an effective physician compensation system, even those physician groups that are most committed to delivering patient-centered, coordinated care run the risk of falling short of their goals.

Since 1997, New West physicians has had a compensation system that rewards performance. We have continually evolved and enhanced our system, and today—with 18 locations and over 100 providers—we are the largest primary care physician medical group practice in Colorado. We employ an integrated team of board-certified family practice and internal medicine physicians, physician assistants, and nurse practitioners; a team of

dedicated hospitalists who serve five contracted hospitals; and specialists in cardiology, gastroenterology, neurology, and endocrinology, as well as behavioral health clinicians and full-time psychiatrists.

We are recognized for our dual focus on high-quality care and care efficiency. the key to our success is how we reward our physicians.

THe MAnAGeD CARe inCenTive PlAn

Our physician bonus plan provides a detailed calculation that guides how all bonuses are distributed to physicians.

“Giving physicians a strong voice in designing and maintaining a compensation plan leads to greater support, not to mention a better plan.”

CapG Member SpotlightPearls of Physician Compensation

Known as the Managed Care Incentive plan, we have found it a highly effective tool for supporting value-based initiatives. all bonuses and shared savings received from both the Medicare risk contract and commercial aCOs are run through this calculation.

Bonuses are distributed based on a four-part formula:

• Quality: 13 percent. Quality includes two different quality studies each year, as determined by the Medical Management Committee, and patient satisfaction scores. patient satisfaction surveys are conducted annually by an outside firm and study key performance areas affecting the patient experience, including access, staff and physician performance, communication, billing, facility, overall satisfaction, teamwork, and willingness to recommend to others.

• Citizenship: 1 percent. this is based on physician participation in New West meetings.

• Even Split: 43 percent. this amount is split evenly among practice physicians based on risk-adjusted per member per month (pMpM). Splitting a portion of the bonus revenues evenly among physicians helps to protect practices from the variation in the type of patients seen. New West also protects physicians against unexpectedly sick patients by using a catastrophic stop-loss for utilization metrics.

• Utilization: 43 percent. Utilization metrics are awarded more abundantly than quality metrics because the large majority of our bonus revenues are generated by utilization practices that eliminate unnecessary care.

Bonuses are distributed quarterly and make up about 35 percent of total physician compensation. Utilization and quality scores are transparent, which greatly influences physician behavior—as much if not more than the financial bonus.

New West’s Managed Care Incentive plan was originally developed and is continually refined by our Compensation Committee, one of New West’s five board committees. the committee, which is made up of physician representatives from each practice and meets quarterly, has frequently modified the plan to increase effectiveness and resolve physician concerns.


Based on our experience over nearly 20 years, there are four keys to establishing a successful physician compensation system:

1. physician involvement. people support what they create. We have found that giving physicians a strong voice in designing and maintaining a compensation plan leads to greater support, not to mention a better plan. In the beginning stages, our physicians were concerned that the geographic diversity of patients would impact the metrics. In response, we hired a socioeconomic statistician who determined that the socioeconomic factors found in the zip codes around the New West sites did not affect quality measure outcomes.

physicians were also concerned that quality measures would be skewed by patients with severe problems. as a result, we created a catastrophic stop-loss—removing high-cost patients from the incentive calculation.

2. Accurate, Actionable Data. We make it a priority to provide our physicians with data that they can use to make specific, high-impact changes in their practice to improve

patient health and outcomes. Our Bench to Bedside program is a key component of this. Bench to Bedside activates high-quality, evidence-based medicine practices in 12 weeks—compared with a more typical timeframe of up to five years.

Our first outcomes trial using this program was in 1997, immediately following the publication of a study in the British Medical Journal. the study looked at the safety and efficacy of outpatient treatment of deep venous thrombosis (DVt). at the time, DVt was routinely treated with a five-to-seven-day hospital stay. Within 12 weeks of the publication, we had developed an outpatient algorithm and shared it with our hospitalist service and emergency room physicians. From that point forward, we treated DVt routinely as an outpatient, with improvements in both cost and outcomes. It was several years before this became the standard of care in the community.

3. Transparency. We are deeply committed to transparency. all quality, clinical outcome, and efficiency data are shared on a quarterly basis in an un-blinded format. this means that all providers view their data alongside their peers’ data within New West physicians—and when available, with community and literature best practice results. We share data in open forums at committee and shareholder meetings. Over time, this transparency has resulted in the top performers establishing best practices to bring up lower performers, markedly enhancing total group performance.

all committee meetings are open to all providers who want to attend. any provider can submit an agenda item to a committee meeting, and we publish minutes of all meetings—including the executive Committee—to all providers.

4. Culture of Accountability. the sustaining force of New West physicians is a strong culture of accountability. this is why quality and patient satisfaction are factored into each physician’s bonus. With no priorities competing with the cost-effective delivery of high-quality medical care, our decision-making is clear and focused. Our internal and external transparency assures confidence and provider satisfaction. provider satisfaction translates into engaged and motivated individuals who constantly strive to raise the bar of their chosen art: the practice of primary care medicine.

SuMMARy

Because New West has had a physician incentive plan in place for nearly our entire lifespan, it’s impossible to know how much of our success is due to the plan. But I feel very confident that the plan has had a definite impact, especially when we compare ourselves with other practices. Since 1997, New West’s commercial cost of care has remained 11 to 15 percent below averages in the Denver metro area. In addition, our 30-day readmission rate for Medicare patients is 7.17 percent, compared with a national average of about 17 to 18 percent. o

Managed Care Incentive PlanIncentive = 35 percent of total compensation

Equal distributionRisk adjusted per member per month, split evenly among each practice’s physiciansQuality

• Two quality measures each year• Patient satisfaction survey scores

CitizenshipMeeting participation

UtilizationPMPM costs by individual provider for hospital, professional and pharmacy

13%

1%

43%

43%

Excluded:• Calculations for patients who have incurred >$50k in total claims in a 12-month period, >$12.5k for professional services, and >$6k for pharmacy.• Lists of drugs that are beyond the PCP's control.

Medicare 30-day Readmission Rate

0

5

10

15

20

New West Nationalaverage

7.1%

17-18%

Commercial Cost of Care, 2016

0

50

100

150

200

250

300

350

New West Denver metro

average

$305 pmpm

$342pmpm

Based on data from Cigna


More than ever, physicians are focusing on treatment plans that include the kind of care patients need at home. however, physicians face potential liability when patients refuse offered help or neglect to follow up as instructed.

If a patient sues, even a verdict in favor of the physician does not negate the time, expense, and emotional impact of a lawsuit. Consider this example: a 67-year-old male with a history of obesity, hypertension, hypercholesterol, atrial fibrillation and cardiovascular disease had seen the same physician for 20 years. During one hospitalization, the patient was put on the blood thinner Coumadin. the physician and the discharge nurse both educated the patient and his wife about the risks of Coumadin use and the importance of having blood work done every month.

Nevertheless, the patient did not keep the first appointment for the monthly blood test (INr). the physician’s staff called to schedule a follow-up visit, but the patient did not return the call. two days following the call, the patient fell at home. his wife took him to the emergency department (eD), where she told the staff that she had been unable to drive him to his appointment for blood work, but she had made sure he took his Coumadin as prescribed. the patient’s INr was extremely elevated with a reading of 8.8. he was diagnosed with a bilateral subdural hematoma and underwent a bilateral craniotomy. he was discharged to home but, due to problems with his coordination and confusion, he visited the eD several more times over the next few months.

the patient sued for malpractice, claiming the physician failed to properly manage the medication regimen and to monitor blood levels, resulting in the fall, subsequent injury, and poor recovery. he also claimed the doctor failed to warn him of the risk of bleeding from the Coumadin.

the case went to trial. Because of the doctor’s thorough documentation, the jury agreed that he had properly educated the patient and made the right resources available to monitor the effects of the Coumadin. the jury found that the patient’s failure to schedule his lab and follow-up appointments caused the injury and, therefore, found in favor of the physician.

While this patient failed to follow physician instructions, other homebound patients simply refuse any help. a recent study1 found that between 6 percent and 28 percent of patients eligible for home healthcare refuse these services. Similar trends are seen with other types of assistance for patients at home. patients often say they are managing just fine and don’t need help, while others don’t want strangers in their homes or worry about the cost of copays for home care. that means some patients are not getting the follow-up and supportive care that the doctor outlined in the care plan. and when the patient doesn’t follow up, it can put the physician at risk.

Physicians Can be at Risk When Homebound Patients Refuse HelpBY rOBIN DIaMOND, MSN, JD, rN

“The potential malpractice risks to physicians are increasing as more care is moved from a healthcare setting to the patient’s home.”

patient behaviors were contributing factors in 25 percent of internal medicine closed claims2 studied by the Doctors Company. Of these factors, noncompliance with the treatment plan was the most common, accounting for 9 percent of internal medicine claims, followed by 7 percent of claims resulting from patient failure to make a follow-up appointment or referral, and 4 percent from failure to take medications as prescribed.

the potential malpractice risks to physicians are increasing as more care is moved from a healthcare setting to the patient’s home. Following these tips can help reduce risks when treating homebound patients:

• Conduct a risk analysis to determine how likely the patient is to comply with instructions. Consider the following: patient’s age, ability to drive, socioeconomic status, whether patient lives alone, and history of failing to comply with appointments or medication instructions.

• Document that:

o the patient received proper discharge instructions.

o resources were made available to overcome compliance challenges, and the physician or practice made a good-faith effort to follow up and intervene if the patient was not in compliance.

• Schedule the follow-up appointment before the patient leaves the office. Give the patient contact information for the community home-health resources.

• educate the patient about why community resources are provided and draw a distinction between what is and is not offered.

patient reluctance to follow the discharge plan is often caused by lack of understanding about

what type of follow-up care is needed. taking time to document patient discussions gives homecare providers valuable information to ensure patients are following the plan—and will also demonstrate, in the event of a lawsuit, the high quality of care provided. o

Robin Diamond, MSN, JD, RN, is Senior Vice President of Patient Safety and Risk Management, The Doctors Company.

References1“Patients Who Refuse Home Health Are More Likely to be Readmitted,” Home Health News, May 2017, http://ahhqi.org/media-center/110

2“Internal Medicine Closed Claim Study,” The Doctors Company, September 2016. http://www.thedoctors.com/KnowledgeCenter/PatientSafety/articles/Internal-Medicine-Closed-Claims-Study


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oRGanIZatIonal membeRs

advanced medical management, Inc.Kathy hegstrom, presidentaccess Medical Group • Community Care Ipa • MediChoice Ipa • Seoul Medical Group

advantage medical Group, llcarcilio alvarado, MD, presidentMaria Melendez, Vp of Operations

adventist Health Physicians network IPaarby Nahapetian, MD, CMOJim agronick, Vp – Ipa Operations

affinity medical Grouprichard Sankary, MD, presidentScott ptacnik, COO

agilon HealthStuart levine, MD, Chief Innovation Officer & CMOliz hernandez, project Manager

alameda Health PartnersWilliam peruzzi, MD, ChairmanDavid Cox, treasurer and CFO

allcare IPaMatt Coury, CeOrandy Winter, MD, president

allied Physicians of californiathomas lam, MD, CeOKenneth Sim, MD, CFO

allina Health systemrod Christensen, MD, Vp of Medical OperationsBrian rice, MD, Vp Network/aCO Integration

altamed Health services corporation *Castulo de la rocha, JD, president and CeOalex Chen, MD, Interim Chief Medical Officer

angel medical GroupMichael Gitter, MD, presidentCarl Westerhoff, executive Vice president

applecare medical Group, Inc.trish Baesemann, presidentGeorge Christides, MD, CMO

arizona Health advantage, Inc.amish purohit, MD, CMO

austin Regional clinic *Norman Chenven, MD, CeO and Founderanas Daghestani, MD, president & CeO

bakersfield family medical centerCarol l. Sorrell, rN, COOJu hwan lee, MD, Medical Director

bayhealth Physician alliance, llcevan W. polansky, JD, executive DirectorJoseph M. parise, DO, Medical Director

beaver medical Group *John Goodman, president and CeOraymond Chan, MD, Vp Medical admin/CMO of epic health plan

brown & toland Physicians *richard Fish, CeO

california Pacific Physicians medical Group, Inc.Dien V. pham, MD, CeOCarol houchins, administrator

canopy HealthJoel a. Criste, CeOMargaret Durbin, MD, CMO

caremore medical GroupSachin Jain, CeOtom tancredi, Director of practice Operations

caremount medical, P.c.Scott D. hayworth, MD, president & CeOKevin J. Conroy, CFO & Chief population health Officer

catholic Health Initiatives *robert Weil, MD, Chief Medical OfficerDon lovasz, president, Clinically Integrated Network

architrave health • arkansas health Network • Colorado health Neighborhoods • KentuckyOne health partners • Mercy health Network • Mission healthCare Network • primeCare Select • St. luke’s health Network • trihealth • UniNet

cedars-sinai medical Group *Stephen C. Deutsch, MD, Chief Medical DirectorJohn Jenrette, MD, executive Vp, Medical Network

central ohio Primary care Physicians Inc. *J. William Wulf, MD, CeOlarry Blosser, MD, Corporate Medical Director

central oregon Independent Practice associationDivya Sharma, MD, Medical DirectorKim Bangerter, executive Director

children’s Physicians medical Groupleonard Kornreich, MD, president and CeO

chinese american IPaGeorge liu, MD, president & CeOpeggy Sheng, COO

chinese community Health care associationJohn M. Williams, pharmD, CeOpolly Chen, Director of Operations

choice medical GroupManmohan Nayyar, MD, presidentMarie langley, Ipa administrator

cigna medical GroupKevin ellis, DO, CMO

citrus valley Independent PhysiciansGurjeet Kalkat, MD, executive Medical DirectorMartin Kleinbart, DpM, Chief Strategy Officer

colorado Permanente medical Group, P.c.Margaret Ferguson, MD, president & executive Medical DirectorClaire tamo, CFO and Vp, Business Operations

comprehensive Geriatric care of san JuanMaria elena Narvaez, MD, CeOMilagros I Silva, Ipa Operations administrator

conifer Health solutionsMegan North, CeO

altaMed health Services • exceptional Care Medical Group • Family Choice Medical Group • Family health alliance • Mid Cities Ipa • OmniCare Medical Group • premier Care of Northern California • Saint agnes Medical Group

davita Healthcare Partners *Don rebhun, MD, Corporate Medical DirectorJim rechtin, SVp Corporate Strategy

aBQ health partners, Division of DaVita healthCare partners (NM) • Colorado Springs health partners (CO) • healthCare partners (Ca) • healthCare partners Nevada (NV) • healthCare partners South Florida (Fl) • JSa Medical Group, Division of DaVita healthCare partners (Fl) • the everett Clinic (Wa)

desert oasis HealthcareDan Frank, COOMarc hoffing, MD, Medical Director

dfW Healthcare Partners llcOsehotue Okojie, MD, ChairwomanJosh Cook, president

dignity HealthBruce Swartz, SVp, physician Integration

east coast medical services, Inc.Ismary Gonzalez, MD, president

edinger medical GroupDenise McCourt, COOMatthew C. Boone, MD, executive Medical Director

el Paso Integral care, IParafael armendariz, DO, presidenttony Martinez, administrator

equality Health – q Pointpedro rodriguez, hMa Board MemberMark hillard, president

everett clinic, P.s., the *al Fisk, MD, CMOadrianne Wagner, associate administrator for Quality Improvement

facey medical foundation *David Mast, Chief executive, Medical Group Foundations erik Davydov, MD, Medical Director

Golden empire managed care, Inc.Michael Myers, CeO

Good samaritan medical Practice associationNupar Kumar, MD, Medical Director

Greater newport Physicians medical Group, Inc. *Diane laird, CeOadam Solomon, MD, CMO

Guthrie medical Group, Inc. *Joseph a. Scopelliti, MD, president & CeOFrederick J. Bloom, MD, president

Hawaii Pacific HealthKenneth B. robbins, MD, CMOMaureen Flannery, Vp, Clinic Operations

Healthcare Partners, IPaJoseph Cervia, MD, aahIVS regional Medical Directoredward Mirzabegian, Chief Operating Officer

Heritage Provider network *richard Merkin, MD, presidentrichard lipeles, COO

affiliated Doctors of Orange County • arizona priority Care plus • Bakersfield Family Medical Group • California Coastal physician Network • California Desert Ipa • Coastal Communities physician Network • Desert Oasis healthcare • Greater Covina Medical Group • healthCare partners, Ipa, aZ & NY • heritage physician Network • heritage Victor Valley Medical Group • high Desert Medical Group • lakeside Community healthcare • lakeside Medical Group • regal Medical Group • Sierra Medical Group

High desert medical GroupCharles lim, MD, FaCp, Medical Directoranthony Dulgeroff, MD, assistant Medical Director

Hill Physicians medical Group, Inc. *David Joyner, CeOamir Sweha, MD, CMO

Innovare Health advocatesCharles Willey, MD, president & CeOpaul Beuttenmuller, CFO

In salud, Inc.armando riega, presidentCarmen ramos, Cpa, executive Director


Iora Health Inc.rushika Fernadopulle, CeODave Fielding, CFO

Jade Health care medical Group, Inc.edward Chow, MD, president & CeOthomas Woo, Manager of Operations

Jefferson Healthanne Docimo, MD, eVp, enterprise CMOrichard Kwei, SVp, Value Based Care & Network performance

John muir Physician network *lee huskins, president & CaOravi hundal, MD, CFO

Key medical Group, Inc.Steve Beargeon, CeOOnsy Said, MD, Medical Director

lakeside community HealthcareJonathan Gluck, Counsel

lakeside medical Group, Inc.

lakewood IPaVarsha Desai, COOalamitos Ipa • St. Mary Ipa • Brookshire Ipa

leon medical centers, Inc.rafael Mas, MD, SVp & CMOJulio G. rebull, Jr., SVp

loma linda university Health careJ. todd Martell, MD, Medical Director

managed care management and educational, llcluis Deliz Varela, MD, Medical DirectorGuido lugo Modesto, esq., administrator

martin luther King, Jr. community medical GroupJohn Fisher, MD, MBa, presidentlaurie Gallagher, practice administrator

maverick medical GroupMark C. Marten, CeOWarren hosseinion, MD, Chairman

medicos selectos del norte, Inc.Mildalias Dominguez pascual, MD, presidentFernando a. Garcia Cruz, MD

medPoInt managementKimberly Carey, presidentrick powell, MD, CMO

accountable health Care Ipa • Bella Vista Medical Group Ipa • Centinela Valley Ipa • el proyecto Del Barrio, Inc. • Global Care Medical Group • healthCare la, Ipa • Jewish home for the aging Ipa • pioneer provider Network, a Medical Group, Inc. • premier physicians Network • prospect Medical Group, Inc. • redwood Community health Network • Watts healthcare Corporation

memorialcare medical Group *Mark Schafer, MD, CeOlaurie Sicaeros, Chief Operating Officer, Vp of physician alignment

mercy Health PhysiciansMichele Montague, COO

meritage medical networkWojtek Nowak, CeOJ. David andrew, MD, Medical Director

methodist lebonheurann D. Brown, MD, Vp practice transformation & InnovationWilliam Breen, SVp, physician alignment

mid-atlantic Permanente medical Group, P.c.Bernadette loftus, MD, associate executive Director for MaSJessica locke, Special assistant

molina medical centers *Keith Wilson, MD, Vice president of Clinical ServicesCarrie harris-Muller, SVp Care Delivery & Strategic partnerships

monarch Healthcare *Bart asner, MD, CeOray Chicoine, president and COO

monterey bay Independent Physician associationJames N. Gilbert, MDMichele Wadsworth, Network Management associate

mount sinai Health Partners *andrew Snyder, MD, president MShp, eVp & Chief Clinical Integration Officer, MShSNiyum Gandhi, eVp & Chief population health Officer

mso of Puerto Rico *richard Shinto, MD, CeOraul Montalvo, MD, president

muir medical Group, IPaUte Burness, rN, CeOSteve Kaplan, MD, president

namm california *leigh hutchins, CeOVerni Jogaratnam, MD, CMO

Coachella Valley physicians of primeCare, Inc. • empire physicians Medical Group • Mercy physicians Medical Group • primary Care associated Medical Group, Inc. • primeCare Medical Group of Chino • primeCare Medical Network, Inc. • primeCare of Citrus Valley • primeCare of Corona • primeCare of hemet Valley Inc • primeCare of Inland Valley • primeCare of Moreno Valley • primeCare of redlands • primeCare of riverside • primeCare of San Bernardino • primeCare of Sun City • primeCare of temecula • redlands Family practice Medical Group, Inc.

new england quality care allianceJoseph Frolkis, MD, president & CeOMeg Costello, COO

new West Physicians, P.c. *ruth Benton, CeOKen Cohen, MD, CMO

northwest Permanente, P.c.harry Stathos, Vp and CFO

northwest Physicians network of Washington, llcrick MacCornack, CeOScott Kronlund, MD, CMO

oak street Healthterry Olsen, MD, SVp, accountable CareDrew Crenshaw, Vp, population health

omnicare medical Grouptoni Chavis, MD, presidentashok raheja, MD, Medical Director

one medical Grouptom lee, MD, Founder & CeOBrendhan Green, Vp Contracting & reimbursement Strategy

Pediatric associatespeter Shulman, MD, CeOScott Farr, COO

Peoples Health networkWarren Murrell, president and CeOBrent Wallis, MD, Medical Director

health prime, l.l.C. • Independent physician association of New Orleans, Inc. • Memorial Independent physician association, Inc. • North Shore Independent physician association, Inc. • pontchartrain Ipa, Inc. • South louisiana Independent physician association • University Medical Group, l.l.C.

the Permanente medical Group, Inc.*Michelle Caughey, MD, associate executive Directortraci r. perry, Director, tpMG, advocacy and political affairs

PHm multisalud, llcroberto l. Bengoa lopez, presidentlynnette Ortiz, MD, Medical Director

advantage Medical Group • advantage Medical Group • alianza de Medicos del Sureste • Centro de Medicina Familiar del Norte • Centro de Medicina primaria advantage del Norte • Centros Medicos Unidos del Oeste • G.M.D.C., Inc • Grupo advantage del Oeste • Grupo Medico de G.M.B., Inc • Grupo Medico de Orocovis

Physicians datatrustlisa Serratore, COOKathi toliver, Vp of Ipa administration

Greater tri-Cities Ipa • Noble aMa Ipa • St. Vincent Ipa

Physicians choice medical Group of san luis obispoJohn Okerblom, MD, presidentBarbara Cheever, executive Director

Physicians medical Group of santa cruz county *Marvin labrie, CeONancy Greenstreet, MD, Medical Director

Physicians choice medical Group of santa mariaJohn Okerblom, MD, presidentBarbara Cheever, executive Director

Physicians of southwest Washington, llcMelanie Matthews, CeOGary r. Goin, MD, president

PIH Health Physiciansrosalio J. lopez, MD, SVp & CMOandrew Zwers, Vp of Group Operations

Pioneer medical Group, Inc. *tom Mahowald, CeOJerry Floro, MD, president

the Portland clinicDick Clark, CeOJeffrey Cleven, MD, CMO

Preferred IPa of californiaMark amico, MD, Medical DirectorZahra Movaghar, administrator

Primary care of st. louis, llcBruce J. Berwald, MD, presidentJoy Strathman

Primed PhysiciansMark Couch, MD, presidentrobert Matthews, Vp of Quality

Privia medical Group llcClay ackerly, MD, Chief Medical OfficerGraham Glaka, Vp, New product Development

Prospect medical Group *Jeereddi prasad, MD, president/acting CMO

aMVI/prospect Medical Group prospect • Genesis healthcare of Southern California, Inc., a Medical Group • Nuestra Familia Medical Group, Inc. • pomona Valley Medical Group, Inc. • prospect health Source Medical Group, Inc. • prospect Medical Group, Inc. • prospect NWOC Medical Group. Inc • prospect professional Care Medical Group, Inc. • prospect provider Group rI, llC • prospect provider Group Cte, llC • prospect provider Group CtW, llC • prospect provider Group NJ, llC • prospect

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provider Group pa • prospect health Services tX, Inc. • StarCare Medical Group, Inc. • Upland Medical Group, a professional Medical Corporation

Providence Health & services

Providence medical management servicesphil Jackson, Chief Integration and transformation Officer

Korean american Medical Group • providence Care Network

Reliant medical Group, Inc.Michael Sheehy, MD, Chief of population health & analyticsBetsy hampton, Vp of population health

Renaissance Physician organizationClare hawkins, MD, ChairmanWhitney horak, president

River city medical Group, Inc.Kendrick t. Que, COOKeith andrews, MD, Medical Director

Riverside medical clinicJudy Carpenter, president and COOSteven larson, MD, Chairman

Riverside Physician networkhoward Saner, CeOpaul Snowden, CFO

st. Joseph Heritage Healthcare *Kevin Manemann, president and CeODavid Kim, MD, Medical Director

hoag Medical Group • Mission heritage Medical Group • St. Mary high Desert Medical Group

st. vincent IPa medical corporationJeffrey hendel, MD, presidentleesa Johnson, Director of Ipa Operations

san bernardino medical GroupJames Malin, CeOthomas hellwig, MD, president

sansum clinic *Kurt ransohoff, MD, CeO & CMOChad hine, COO

santa clara county IPa (sccIPa)Janet Doherty pulliam, CFO

santé Health system, Inc.Scott B. Wells, CeODaniel Bluestone, MD, Medical Director

seaview IPalynn haas, CeOKooros Samadzadeh, DO, Medical Director

scripps coastal medical centeranthony Chong, MD, CMOtracy Chu, assistant Vice president of Operations

scripps Physicians medical GroupJoyce Cook, CeOJames Cordell, MD, Medical Director

sharp community medical Group *paul Durr, CeOChristopher McGlone, COOGraybill Medical Group • arch health partners

sharp Rees-stealy medical Group *Stacey hrountas, CeOalan Bier, MD, president

signature Partners network *Matthew poffenroth, MD, CeO & CMOanne rieger, COO

southeast Permanente medical Group, Inc., theMichael Doherty, MD, executive Medical Director and Chief of Staff

southern california Permanente medical Group *Diana Shiba, MD, Director of Government relationsVeronica Dela rosa, assistant Medical Group administrator

southwest medical associatesrobert B. McBeath, MD, president & CeOGreg Griffin, COO

summit medical Group, Pa *Jeffrey le Benger, MD, Chairman & CeOJamie reedy, MD, Vp of population health & Quality

sutter Health foundations & affiliated Groups *larry deGhetaldi, MD, Division president, palo alto Medical Foundation

Central Valley Medical Group • east Bay physicians Medical Group • Gould Medical Group • Marin headlands Medical Group • Mills-peninsula Medical Group • palo alto Foundation Medical Group • palo alto Medical Foundation • peninsula Medical Clinic • physician Foundation Medical associates • Sutter east Bay Medical Foundation • Sutter Gould Medical Foundation • Sutter Independent physicians • Sutter Medical Foundation • Sutter Medical Group • Sutter Medical Group of the redwoods • Sutter North Medical Group • Sutter pacific Medical Foundation

swedish medical GroupMeena Mital, MD, Medical DirectorBela Biro, administrative Director, accountable Care Services

synergy Healthcare, llcJames Jones, MD, Chairmanaustin Burrows, Sr. administrator, Careallies

synermed *James Mason, president & CeOJorge Weingarten, MD, CMO

adventist health plan • alpha Care Medical Group • alvarado hospital Medical Center • angeles Ipa • Coordinated Care plan of California • Crown City Medical Group • ehS Inland Valleys Ipa • ehS Medical Group – Central Valley • ehS Medical Group – los angeles • ehS Medical Group – Sacramento • employee health Systems • Ipa of Georgia • MultiCultural Medical Group • pacific alliance Medical Center • torrance hospital Ipa • XiMed

tenet HealthcareKathryne M. McGowan, CeOronald Kaufman, CMO

torrance Hospital IPaNorman panitch, MD, president

tri valley Internal medicine GroupJonathan h. Dinh, MD, CeOKaila t. pollock, COO

triad Healthcare network, llc *Steve Neorr, Vp, executive Director

uc davis HealthMichael hooper, Medical Director, Care Services & Innovationann Boynton, Director, Care Services & Innovation

uc Irvine HealthManuel porto, MD, president & CeONatalie Maton, executive Director of Operations

ucla medical Group *Sam Skootsky, MD, CMOKit Song, MD, Medical Director

usc care medical Group, Inc.rohit Varma, MD, Mph, president

valley care IPaSonya araiza, CeOMichael Swartout, MD, Medical Director

valley organized PhysiciansWilliam torkildsen, MD, ChairmanSarah Wolf, Senior administrator

the vancouver clinic, Inc., P.s. *Mark Mantei, CeO

verity medical foundationeric Marton, CeODean M. Didech, MD, CMO

Washington Permanente medical GroupSteve tarnoff, MD, president & executive Medical DirectorDavid Kauff, MD, Medical Director

Wellmed medical Group, P.a.George M. rapier III, MD, Chairman and CeOCarlos O. hernandez, MD, president

coRPoRate PaRtneRsabbVieanthem Blue Cross of CaliforniaBoehringer Ingelheim pharmaceuticals, Inc.Continuum healthevolent healthhumana, Inc.Merck & Co.Nestle health ScienceNovartis pharmaceuticalsNovo Nordiskpatient-Centered primary Care Collaborativepfizer, Inc.Sanofi, USSCaN health plan

assocIate PaRtneRsarkrayastellas pharma US, Inc.astraZeneca pharmaceuticalsavanir pharmaceuticals, Inc.Bristol-Myers-Squibbeasy Choice health plan, Inc.Genentech, Inc.healthaxis Group, llCIncyte CorporationJohnson & Johnson Family of CompaniesKaufman, hall & associatesKindred healthcare, Inc.lumara healthNatera, Inc.ralphs Grocery CompanySoleo health Inc.Sunovion pharmaceuticals Inc.the Doctors Company

affIlIate PaRtneRsacurus Solutions Inc.alignment healthcarealturaCanvas MedicalChildren’s hospital los angeles Medical GroupCVhCareFinancial recovery Group Inc. (FrG)Manifest MedexMills peninsula Medical GroupMyWoundDoctorNifty after Fifty Monarch llCpartners in Care Foundationpharmacyclics, Inc.redlands Community hospitalSullivanluallin GroupSynergy pharmaceuticalsU.S. advisors, Inc.Ventegra, llC

* Indicates 2017–2018 Board Members

Summer 2017 capg health l 29Fall 2017 capg health l 29

CHOOSE IMBRUVICA® (ibrutinib) FOR:• ORAL, ONCE-DAILY DOSING1 • 8 APPROVALS IN LESS THAN 4 YEARS1-9

• MORE THAN 40,000 US PATIENTS TREATED SINCE APPROVAL10*

Please see additional Important Safety Information and Brief Summary on the following pages.

IMPORTANT SAFETY INFORMATIONWARNINGS AND PRECAUTIONSHemorrhage: Fatal bleeding events have occurred in patients treated with IMBRUVICA®. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA®.

The mechanism for the bleeding events is not well understood.

IMBRUVICA® may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding.

Consider the benefi t-risk of withholding IMBRUVICA® for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA® therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA®. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections.

Monitor and evaluate patients for fever and infections and treat appropriately.

Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 13 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0 to 13%) based on laboratory measurements occurred in patients with B-cell malignancies treated with single agent IMBRUVICA®.

Monitor complete blood counts monthly.

Atrial Fibrillation: Atrial fi brillation and atrial fl utter (range, 6 to 9%) have occurred in patients treated with IMBRUVICA®, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fi brillation. Periodically monitor patients clinically for atrial fi brillation. Patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness) or new onset dyspnea should have an ECG performed. Atrial fi brillation should be managed appropriately, and if it persists, consider the risks and benefi ts of IMBRUVICA® treatment and follow dose modifi cation guidelines.

Hypertension: Hypertension (range, 6 to 17%) has occurred in patients treated with IMBRUVICA® with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA®.

Adjust existing anti-hypertensive medications and/or initiate anti-hypertensive treatment as appropriate.

References: 1. IMBRUVICA® (ibrutinib) Prescribing Information. Pharmacyclics LLC. 2017. 2. Food and Drug Administration, Center for Drug Evaluation and Research. IMBRUVICA® NDA 205552 approval letter, November, 2013. 3. Food and Drug Administration, Center for Drug Evaluation and Research. IMBRUVICA® NDA 205552/Original 2 approval letter, February, 2014. 4. Food and Drug Administration, Center for Drug Evaluation and Research. IMBRUVICA® NDA 205552/S-001 approval letter, July, 2014. 5. Food and Drug Administration, Center for Drug Evaluation and Research. IMBRUVICA® NDA 205552/S-002 approval letter, January, 2015. 6. Food and Drug Administration, Center for Drug Evaluation and Research. IMBRUVICA® NDA 205552/S-007 approval letter, March, 2016. 7. Food and Drug Administration, Center for Drug Evaluation and Research. IMBRUVICA® NDA 205552/S-010, NDA205552/S-013 approval letter, May, 2016. 8. Food and Drug Administration, Center for Drug Evaluation and Research. IMBRUVICA® NDA 205552/S-016 approval letter, January, 2017. 9. Food and Drug Administration, Center for Drug Evaluation and Research. IMBRUVICA® NDA 205552/S-017 approval letter, August, 2017. 10. Data on fi le. Pharmacyclics LLC. 11. Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-2437.

*Based on IMS data November 2013 to date.

Visit IMBRUVICAHCP.com and discover more reasons for making IMBRUVICA® your choice.

B:11.125 inB:8.375 in

T:10.875 inT:8.125 in

S:9.875 inS:7.25 in

Date: 09/12/17 Brand: IMBRUVICA® Colors: CMYK

File Name: PRC-02857_792806_v1a Size: 8.125” x 10.875” Page 1 (RIGHT side of spread) 100, 0, 0, 0 =

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We Are Alexander #: 792806 Pub: CAPG HEALTH (Fall 2017 Issue)

2, 38, 100, 0 =

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To learn more, visit IMBRUVICAHCP.com

IMBRUVICA®: MAKING AN IMPACT ON PATIENTS ACROSS 6 DISEASES1

• Median follow-up was 18 months• With IMBRUVICA®, median PFS was not reached vs 18.9 months

(95% CI: 14.1, 22.0) with chlorambucil• PFS was assessed by an IRC per revised 2008 iwCLL criteria• Patients with del 17p were excluded

• Median follow-up was 28 months• Fewer deaths with IMBRUVICA® were observed; 11 (8.1%) in the

IMBRUVICA® arm vs 21 (15.8%) in the chlorambucil arm

Previously treated patients were also studied in two phase 3 trials and one phase1/b trial.

IMPORTANT SAFETY INFORMATION (CONT’D) WARNINGS AND PRECAUTIONS

Second Primary Malignancies: Other malignancies (range, 3 to 16%) including non-skin carcinomas (range, 1 to 4%) have occurred in patients treated with IMBRUVICA®. The most frequent second primary malignancy was non-melanoma skin cancer (range, 2 to 13%).

Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA® therapy. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions.

Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity: Based on fi ndings in animals, IMBRUVICA® can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA® and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise men to avoid fathering a child during the same time period.

ADVERSE REACTIONS

B-cell malignancies: The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (62%), neutropenia (61%), diarrhea (43%), anemia (41%), musculoskeletal pain (30%), rash (30%), bruising (30%), nausea (29%), fatigue (29%), hemorrhage (22%), and pyrexia (21%).

The most common Grade 3 or 4 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (39%), thrombocytopenia (16%), and pneumonia (10%).

Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 9% (WM [6%] and MZL [13%]) of patients discontinued due to adverse reactions.

cGVHD: The most common adverse reactions (≥20%) in patients with cGVHD were fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%), muscle spasms (29%), stomatitis (29%), nausea (26%), hemorrhage (26%), anemia (24%), and pneumonia (21%).

The most common Grade 3 or 4 adverse reactions (≥5%) reported in patients with cGVHD were fatigue (12%), diarrhea (10%), neutropenia (10%), pneumonia (10%), sepsis (10%), hypokalemia (7%), headache (5%), musculoskeletal pain (5%), and pyrexia (5%).

Twenty-four percent of patients receiving IMBRUVICA® in the cGVHD trial discontinued treatment due to adverse reactions. Adverse reactions leading to dose reduction occurred in 26% of patients.

DRUG INTERACTIONS

CYP3A Inducers: Avoid coadministration with strong CYP3A inducers.

CYP3A Inhibitors: Dose adjustment may be recommended.

SPECIFIC POPULATIONS

Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA® in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA® dose.Please see the Brief Summary on the following pages.

cGVHD=chronic graft versus host disease, CI=confi dence interval, CLL=chronic lymphocytic leukemia, HR=hazard ratio, IRC=Independent Review Committee, iwCLL=International Workshop on CLL, MCL=mantle cell lymphoma, MZL=marginal zone lymphoma, PFS=progression-free survival, SLL=small lymphocytic lymphoma, WM=Waldenström’s Macroglobulinemia.

CR=complete response, IgM=immunoglobulin M, IRC=Independent Review Committee, ORR=overall response rate, PR=partial response, VGPR=very good partial response.

19 of 42 patients achieved a PR and 9 patients achieved a CR.

84% statistically significant reduction in risk of progression or death

N at riskIMBCLB

PFS

(%)

Months

HR=0.16 (95% CI: 0.09, 0.28); P<0.0001

Estimated PFS at 18 months

90% IMBRUVICA®


52% chlorambucil

RESONATETM-2: Multicenter, randomized 1:1, open-label, Phase 3 trial vs chlorambucil in adult frontline patients ≥65 years (N=269)1,11

Responses were assessed by investigators using criteria according to the revised International Working Group criteria for non-Hodgkin’s lymphoma.1

Reduced risk of death by more than half

Phase 2, multicenter, open-label, single-arm trial in previously treated adult patients (N=111)1

The responses were assessed by an IRC using criteria adopted from the International Working Group criteria for malignant lymphoma.1

Phase 2, open-label, multicenter, single-arm trial in adult patients who received at least 1 prior anti-CD20-based therapy (N=63)1

Responses were assessed by investigators and an IRC using criteria adopted from the International Workshop of WM. Responses per IRC are shown above. Response rate=CR+VGPR+PR. CR was defi ned as a resolution of all symptoms, normalization of serum IgM levels with a complete disappearance of IgM paraprotein by immunofi xation, and resolution of any adenopathy or splenomegaly. VGPR was defi ned as ≥90% reduction in serum IgM levels. PR was defi ned as ≥50% reduction in serum IgM levels.10

Phase 2, multicenter, open-label, single-arm trial in previously treated adult patients (N=63)1,10

The responses were assessed by investigators using the 2005 National Institutes of Health (NIH) Consensus Panel Response Criteria with two modifi cations to align with the updated 2014 NIH Consensus Panel Response Criteria.1

Phase 1b/2, open-label, multicenter, single-arm trial in adult patients after failure of fi rst-line corticosteroid therapy (N=42)1

INDICATIONSIMBRUVICA® (ibrutinib) is a once-daily oral therapy indicated for adult patients with:

• Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)

• CLL/SLL with 17p deletion

• Waldenström’s Macroglobulinemia (WM)

• Chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy

• Mantle cell lymphoma (MCL) who have received at least one prior therapy

• Marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy– Accelerated approval was granted for the MCL and MZL

indications based on overall response rate. Continuedapproval for these indications may be contingent upon verifi cation and description of clinical benefi t in confi rmatory trials

Statisticallysignificant

reduction inrisk of death

56%HR=0.44

(95% CI: 0.21, 0.92)

41% of patientscrossed over

to IMBRUVICA®upon disease

progression

Estimated survival ratesat 24 months

IMBRUVICA®(95% CI: 89, 97)

95%

chlorambucil(95% CI: 77, 90)

CLLSLL MCL WM

MZL cGVHD

IMBRUVICA® (N=63)

No patients achieved a CR

†95% CI: 48.8, 73.9

51% PR

11% VGPR

IMBRUVICA® (N=42)§95% CI: 51%, 80%

45% PR

21% CR

IMBRUVICA® (N=63)‡95% CI: 33.4, 59.1

43% PR

3% CR

66%*

ORR

46%‡

ORR67%§

ORR

62%†

ResponseRate

IMBRUVICA® (N=111)*95% CI: 56.2, 74.5

49% PR

17% CR

B:11.125 in

T:10.875 in

T:8.125 in

S:9.875 in

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T:8.125 in

S:7.25 in

B:8.375 in


File Name: PRC-02857_792806_v1a Size: 8.125” x 10.875” Page 2-3 (spread) 100, 0, 0, 0 =


67, 95, 4, 16 =


2, 38, 100, 0 =

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96, 0, 30, 45 =

To learn more, visit IMBRUVICAHCP.com

IMBRUVICA®: MAKING AN IMPACT ON PATIENTS ACROSS 6 DISEASES1

• Median follow-up was 18 months• With IMBRUVICA®, median PFS was not reached vs 18.9 months

(95% CI: 14.1, 22.0) with chlorambucil• PFS was assessed by an IRC per revised 2008 iwCLL criteria• Patients with del 17p were excluded

• Median follow-up was 28 months• Fewer deaths with IMBRUVICA® were observed; 11 (8.1%) in the

IMBRUVICA® arm vs 21 (15.8%) in the chlorambucil arm

Previously treated patients were also studied in two phase 3 trials and one phase1/b trial.

IMPORTANT SAFETY INFORMATION (CONT’D) WARNINGS AND PRECAUTIONS

Second Primary Malignancies: Other malignancies (range, 3 to 16%) including non-skin carcinomas (range, 1 to 4%) have occurred in patients treated with IMBRUVICA®. The most frequent second primary malignancy was non-melanoma skin cancer (range, 2 to 13%).

Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA® therapy. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions.

Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity: Based on fi ndings in animals, IMBRUVICA® can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA® and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise men to avoid fathering a child during the same time period.

ADVERSE REACTIONS

B-cell malignancies: The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (62%), neutropenia (61%), diarrhea (43%), anemia (41%), musculoskeletal pain (30%), rash (30%), bruising (30%), nausea (29%), fatigue (29%), hemorrhage (22%), and pyrexia (21%).

The most common Grade 3 or 4 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (39%), thrombocytopenia (16%), and pneumonia (10%).

Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 9% (WM [6%] and MZL [13%]) of patients discontinued due to adverse reactions.

cGVHD: The most common adverse reactions (≥20%) in patients with cGVHD were fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%), muscle spasms (29%), stomatitis (29%), nausea (26%), hemorrhage (26%), anemia (24%), and pneumonia (21%).

The most common Grade 3 or 4 adverse reactions (≥5%) reported in patients with cGVHD were fatigue (12%), diarrhea (10%), neutropenia (10%), pneumonia (10%), sepsis (10%), hypokalemia (7%), headache (5%), musculoskeletal pain (5%), and pyrexia (5%).

Twenty-four percent of patients receiving IMBRUVICA® in the cGVHD trial discontinued treatment due to adverse reactions. Adverse reactions leading to dose reduction occurred in 26% of patients.

DRUG INTERACTIONS

CYP3A Inducers: Avoid coadministration with strong CYP3A inducers.

CYP3A Inhibitors: Dose adjustment may be recommended.

SPECIFIC POPULATIONS

Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA® in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA® dose.Please see the Brief Summary on the following pages.

cGVHD=chronic graft versus host disease, CI=confi dence interval, CLL=chronic lymphocytic leukemia, HR=hazard ratio, IRC=Independent Review Committee, iwCLL=International Workshop on CLL, MCL=mantle cell lymphoma, MZL=marginal zone lymphoma, PFS=progression-free survival, SLL=small lymphocytic lymphoma, WM=Waldenström’s Macroglobulinemia.

CR=complete response, IgM=immunoglobulin M, IRC=Independent Review Committee, ORR=overall response rate, PR=partial response, VGPR=very good partial response.

19 of 42 patients achieved a PR and 9 patients achieved a CR.

84% statistically significant reduction in risk of progression or death

N at riskIMBCLB

PFS

(%)

Months

HR=0.16 (95% CI: 0.09, 0.28); P<0.0001


90% IMBRUVICA®


52% chlorambucil

RESONATETM-2: Multicenter, randomized 1:1, open-label, Phase 3 trial vs chlorambucil in adult frontline patients ≥65 years (N=269)1,11

Responses were assessed by investigators using criteria according to the revised International Working Group criteria for non-Hodgkin’s lymphoma.1

Reduced risk of death by more than half

Phase 2, multicenter, open-label, single-arm trial in previously treated adult patients (N=111)1

The responses were assessed by an IRC using criteria adopted from the International Working Group criteria for malignant lymphoma.1

Phase 2, open-label, multicenter, single-arm trial in adult patients who received at least 1 prior anti-CD20-based therapy (N=63)1

Responses were assessed by investigators and an IRC using criteria adopted from the International Workshop of WM. Responses per IRC are shown above. Response rate=CR+VGPR+PR. CR was defi ned as a resolution of all symptoms, normalization of serum IgM levels with a complete disappearance of IgM paraprotein by immunofi xation, and resolution of any adenopathy or splenomegaly. VGPR was defi ned as ≥90% reduction in serum IgM levels. PR was defi ned as ≥50% reduction in serum IgM levels.10

Phase 2, multicenter, open-label, single-arm trial in previously treated adult patients (N=63)1,10

The responses were assessed by investigators using the 2005 National Institutes of Health (NIH) Consensus Panel Response Criteria with two modifi cations to align with the updated 2014 NIH Consensus Panel Response Criteria.1

Phase 1b/2, open-label, multicenter, single-arm trial in adult patients after failure of fi rst-line corticosteroid therapy (N=42)1

INDICATIONSIMBRUVICA® (ibrutinib) is a once-daily oral therapy indicated for adult patients with:

• Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)

• CLL/SLL with 17p deletion

• Waldenström’s Macroglobulinemia (WM)

• Chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy

• Mantle cell lymphoma (MCL) who have received at least one prior therapy

• Marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy– Accelerated approval was granted for the MCL and MZL

indications based on overall response rate. Continuedapproval for these indications may be contingent upon verifi cation and description of clinical benefi t in confi rmatory trials

Statisticallysignificant

reduction inrisk of death

56%HR=0.44

(95% CI: 0.21, 0.92)

41% of patientscrossed over

to IMBRUVICA®upon disease

progression

Estimated survival ratesat 24 months

IMBRUVICA®(95% CI: 89, 97)

95%

chlorambucil(95% CI: 77, 90)

CLLSLL MCL WM

MZL cGVHD

IMBRUVICA® (N=63)

No patients achieved a CR

†95% CI: 48.8, 73.9

51% PR

11% VGPR

IMBRUVICA® (N=42)§95% CI: 51%, 80%

45% PR

21% CR

IMBRUVICA® (N=63)‡95% CI: 33.4, 59.1

43% PR

3% CR

66%*

ORR

46%‡

ORR67%§

ORR

62%†

ResponseRate

IMBRUVICA® (N=111)*95% CI: 56.2, 74.5

49% PR

17% CR

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Brief Summary of Prescribing Information for IMBRUVICA® (ibrutinib)IMBRUVICA® (ibrutinib) capsules, for oral useSee package insert for Full Prescribing InformationINDICATIONS AND USAGEMantle Cell Lymphoma: IMBRUVICA is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial [see Clinical Studies (14.1) in Full Prescribing Information].Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: IMBRUVICA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) [see Clinical Studies (14.2) in Full Prescribing Information].Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma with 17p deletion: IMBRUVICA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with 17p deletion [see Clinical Studies (14.2) in Full Prescribing Information].Waldenström’s Macroglobulinemia: IMBRUVICA is indicated for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) [see Clinical Studies (14.3) in Full Prescribing Information].Marginal Zone Lymphoma: IMBRUVICA is indicated for the treatment of adult patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy. Accelerated approval was granted for this indication based on overall response rate [see Clinical Studies (14.4) in Full Prescribing Information]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Chronic Graft versus Host Disease: IMBRUVICA is indicated for the treatment of adult patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy [see Clinical Studies (14.5) in Full Prescribing Information].CONTRAINDICATIONSNoneWARNINGS AND PRECAUTIONSHemorrhage: Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA. The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding [see Clinical Studies (14) in Full Prescribing Information].Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 29% of patients [see Adverse Reactions]. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections. Monitor and evaluate patients for fever and infections and treat appropriately.Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 13 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0 to 13%) based on laboratory measurements occurred in patients with B-cell malignancies treated with single agent IMBRUVICA.Monitor complete blood counts monthly. Atrial Fibrillation: Atrial fibrillation and atrial flutter (range, 6 to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness) or new onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately, and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines [see Dosage and Administration (2.3) in Full Prescribing Information]. Hypertension: Hypertension (range, 6 to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing anti-hypertensive medications and/or initiate anti-hypertensive treatment as appropriate. Second Primary Malignancies: Other malignancies (range, 3 to 16%) including non-skin carcinomas (range, 1 to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 2 to 13%).

Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate. Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Administration of ibrutinib to pregnant rats and rabbits during the period of organogenesis caused embryofetal toxicity including malformations at exposures that were 2-20 times higher than those reported in patients with hematologic malignancies. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations].ADVERSE REACTIONSThe following adverse reactions are discussed in more detail in other sections of the labeling:• Hemorrhage [see Warnings and Precautions]• Infections [see Warnings and Precautions]• Cytopenias [see Warnings and Precautions]• Atrial Fibrillation [see Warnings and Precautions]• Hypertension [see Warnings and Precautions]• Second Primary Malignancies [see Warnings and Precautions]• Tumor Lysis Syndrome [see Warnings and Precautions]Clinical Trials Experience: Because clinical trials are conducted under widely variable conditions, adverse event rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice.Mantle Cell Lymphoma: The data described below reflect exposure to IMBRUVICA in a clinical trial (Study 1104) that included 111 patients with previously treated MCL treated with 560 mg daily with a median treatment duration of 8.3 months.The most commonly occurring adverse reactions (≥ 20%) were thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory tract infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting and decreased appetite (see Tables 1 and 2).The most common Grade 3 or 4 non-hematological adverse reactions (≥ 5%) were pneumonia, abdominal pain, atrial fibrillation, diarrhea, fatigue, and skin infections.Fatal and serious cases of renal failure have occurred with IMBRUVICA therapy. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 9% of patients.Adverse reactions from the MCL trial (N=111) using single agent IMBRUVICA 560 mg daily occurring at a rate of ≥ 10% are presented in Table 1.

Table 1: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with MCL (N=111)

Body System Adverse ReactionAll Grades

(%)Grade 3

or 4 (%)

Gastrointestinal disorders

DiarrheaNauseaConstipationAbdominal painVomitingStomatitisDyspepsia

51312524231711

5005010

Infections and infestations

Upper respiratory tract infectionUrinary tract infectionPneumoniaSkin infectionsSinusitis

34

14141413

0

3751

General disorders and administration site conditions

FatiguePeripheral edemaPyrexiaAsthenia

41351814

5313

Skin and subcutaneous tissue disorders

BruisingRashPetechiae

302511

030

Musculoskeletal and connective tissue disorders

Musculoskeletal painMuscle spasmsArthralgia

371411

100

Respiratory, thoracic and mediastinal disorders

DyspneaCoughEpistaxis

271911

400

IMBRUVICA® (ibrutinib) capsules IMBRUVICA® (ibrutinib) capsules IMBRUVICA® (ibrutinib) capsules

Table 1: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with MCL (N=111) (continued)

Body System Adverse Reaction

All Grades (%)

Grade 3 or 4 (%)

Metabolism and nutrition disorders

Decreased appetiteDehydration

2112

24

Nervous system disorders

DizzinessHeadache

1413

00

Table 2: Treatment-Emergent* Hematologic Laboratory Abnormalities in Patients with MCL (N=111)

Percent of Patients (N=111)All Grades

(%)Grade 3 or 4

(%)Platelets Decreased 57 17Neutrophils Decreased 47 29Hemoglobin Decreased 41 9

* Based on laboratory measurements and adverse reactions

Ten patients (9%) discontinued treatment due to adverse reactions in the trial (N=111). The most frequent adverse reaction leading to treatment discontinuation was subdural hematoma (1.8%). Adverse reactions leading to dose reduction occurred in 14% of patients.Patients with MCL who develop lymphocytosis greater than 400,000/mcL have developed intracranial hemorrhage, lethargy, gait instability, and headache. However, some of these cases were in the setting of disease progression.Forty percent of patients had elevated uric acid levels on study including 13% with values above 10 mg/dL. Adverse reaction of hyperuricemia was reported for 15% of patients.Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: The data described below reflect exposure in one single-arm, open-label clinical trial (Study 1102) and three randomized controlled clinical trials (RESONATE, RESONATE-2, and HELIOS) in patients with CLL/SLL (n=1278 total and n=668 patients exposed to IMBRUVICA). Study 1102 included 51 patients with previously treated CLL/SLL, RESONATE included 391 randomized patients with previously treated CLL or SLL who received single agent IMBRUVICA or ofatumumab, RESONATE-2 included 269 randomized patients 65 years or older with treatment naïve-CLL or SLL who received single agent IMBRUVICA or chlorambucil, and HELIOS included 578 randomized patients with previously treated CLL or SLL who received IMBRUVICA in combination with bendamustine and rituximab or placebo in combination with bendamustine and rituximab. The most commonly occurring adverse reactions in Studies 1102, RESONATE, RESONATE-2, and HELIOS in patients with CLL/SLL receiving IMBRUVICA (≥ 20%) were neutropenia, thrombocytopenia, anemia, diarrhea, musculoskeletal pain, nausea, rash, bruising, fatigue, pyrexia and hemorrhage. Four to 10 percent of patients receiving IMBRUVICA in Studies 1102, RESONATE, RESONATE-2, and HELIOS discontinued treatment due to adverse reactions. These included pneumonia, hemorrhage, atrial fibrillation, rash and neutropenia (1% each). Adverse reactions leading to dose reduction occurred in approximately 6% of patients.Study 1102: Adverse reactions and laboratory abnormalities from the CLL/SLL trial (N=51) using single agent IMBRUVICA 420 mg daily in patients with previously treated CLL/SLL occurring at a rate of ≥ 10% with a median duration of treatment of 15.6 months are presented in Tables 3 and 4.

Table 3: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with CLL/SLL (N=51) in Study 1102


All Grades

(%)

Grade 3 or 4 (%)


DiarrheaConstipationNauseaStomatitisVomitingAbdominal painDyspepsia

59222020181412

4220200


Upper respiratory tract infectionSinusitisSkin infectionPneumoniaUrinary tract infection

47221612

12

266

10

2

Table 3: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with CLL/SLL (N=51) in Study 1102 (continued)


All Grades

(%)

Grade 3 or 4 (%)


FatiguePyrexia Peripheral edemaAstheniaChills

3324221412

62060


Bruising Rash Petechiae

512516

200


CoughOropharyngeal painDyspnea

221412

000


Musculoskeletal painArthralgiaMuscle spasms

252418

602


DizzinessHeadache

2018

02


Decreased appetite 16 2

Neoplasms benign, malignant, unspecified

Second malignancies*

12* 0

Vascular disorders Hypertension 16 8* One patient death due to histiocytic sarcoma.

Table 4: Treatment-Emergent* Hematologic Laboratory Abnormalities in Patients with CLL/SLL (N=51) in Study 1102

Percent of Patients (N=51)All Grades (%) Grade 3 or 4 (%)

Platelets Decreased 69 12Neutrophils Decreased 53 26Hemoglobin Decreased 43 0

* Based on laboratory measurements per IWCLL criteria and adverse reactions.

RESONATE: Adverse reactions and laboratory abnormalities described below in Tables 5 and 6 reflect exposure to IMBRUVICA with a median duration of 8.6 months and exposure to ofatumumab with a median of 5.3 months in RESONATE in patients with previously treated CLL/SLL.

Table 5: Adverse Reactions Reported in ≥ 10% of Patients and at Least 2% Greater in the IMBRUVICA Treated Arm in Patients

with CLL/SLL in RESONATE

Body SystemAdverse Reaction

IMBRUVICA(N=195)

Ofatumumab(N=191)

All Grades(%)

Grade 3 or 4(%)

All Grades(%)

Grade 3 or 4(%)


Diarrhea 48 4 18 2Nausea 26 2 18 0Stomatitis* 17 1 6 1Constipation 15 0 9 0Vomiting 14 0 6 1


Pyrexia 24 2 15 1Infections and infestations

Upper respiratory tract infection 16 1 11 2Pneumonia* 15 10 13 9Sinusitis* 11 1 6 0Urinary tract infection 10 4 5 1


Rash* 24 3 13 0Petechiae 14 0 1 0Bruising* 12 0 1 0

B:11.125 in

T:10.875 in

T:8.125 in

S:9.875 in

S:7.25 in

T:8.125 in

S:7.25 in

B:8.375 in




67, 95, 4, 16 =


2, 38, 100, 0 =

50, 0, 100, 0 =

96, 0, 30, 45 =

Brief Summary of Prescribing Information for IMBRUVICA® (ibrutinib)IMBRUVICA® (ibrutinib) capsules, for oral useSee package insert for Full Prescribing InformationINDICATIONS AND USAGEMantle Cell Lymphoma: IMBRUVICA is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial [see Clinical Studies (14.1) in Full Prescribing Information].Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: IMBRUVICA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) [see Clinical Studies (14.2) in Full Prescribing Information].Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma with 17p deletion: IMBRUVICA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with 17p deletion [see Clinical Studies (14.2) in Full Prescribing Information].Waldenström’s Macroglobulinemia: IMBRUVICA is indicated for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) [see Clinical Studies (14.3) in Full Prescribing Information].Marginal Zone Lymphoma: IMBRUVICA is indicated for the treatment of adult patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy. Accelerated approval was granted for this indication based on overall response rate [see Clinical Studies (14.4) in Full Prescribing Information]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Chronic Graft versus Host Disease: IMBRUVICA is indicated for the treatment of adult patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy [see Clinical Studies (14.5) in Full Prescribing Information].CONTRAINDICATIONSNoneWARNINGS AND PRECAUTIONSHemorrhage: Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA. The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding [see Clinical Studies (14) in Full Prescribing Information].Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 29% of patients [see Adverse Reactions]. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections. Monitor and evaluate patients for fever and infections and treat appropriately.Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 13 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0 to 13%) based on laboratory measurements occurred in patients with B-cell malignancies treated with single agent IMBRUVICA.Monitor complete blood counts monthly. Atrial Fibrillation: Atrial fibrillation and atrial flutter (range, 6 to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness) or new onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately, and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines [see Dosage and Administration (2.3) in Full Prescribing Information]. Hypertension: Hypertension (range, 6 to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing anti-hypertensive medications and/or initiate anti-hypertensive treatment as appropriate. Second Primary Malignancies: Other malignancies (range, 3 to 16%) including non-skin carcinomas (range, 1 to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 2 to 13%).

Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate. Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Administration of ibrutinib to pregnant rats and rabbits during the period of organogenesis caused embryofetal toxicity including malformations at exposures that were 2-20 times higher than those reported in patients with hematologic malignancies. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations].ADVERSE REACTIONSThe following adverse reactions are discussed in more detail in other sections of the labeling:• Hemorrhage [see Warnings and Precautions]• Infections [see Warnings and Precautions]• Cytopenias [see Warnings and Precautions]• Atrial Fibrillation [see Warnings and Precautions]• Hypertension [see Warnings and Precautions]• Second Primary Malignancies [see Warnings and Precautions]• Tumor Lysis Syndrome [see Warnings and Precautions]Clinical Trials Experience: Because clinical trials are conducted under widely variable conditions, adverse event rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice.Mantle Cell Lymphoma: The data described below reflect exposure to IMBRUVICA in a clinical trial (Study 1104) that included 111 patients with previously treated MCL treated with 560 mg daily with a median treatment duration of 8.3 months.The most commonly occurring adverse reactions (≥ 20%) were thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory tract infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting and decreased appetite (see Tables 1 and 2).The most common Grade 3 or 4 non-hematological adverse reactions (≥ 5%) were pneumonia, abdominal pain, atrial fibrillation, diarrhea, fatigue, and skin infections.Fatal and serious cases of renal failure have occurred with IMBRUVICA therapy. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 9% of patients.Adverse reactions from the MCL trial (N=111) using single agent IMBRUVICA 560 mg daily occurring at a rate of ≥ 10% are presented in Table 1.

Table 1: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with MCL (N=111)

Body System Adverse ReactionAll Grades

(%)Grade 3

or 4 (%)


DiarrheaNauseaConstipationAbdominal painVomitingStomatitisDyspepsia

51312524231711

5005010


Upper respiratory tract infectionUrinary tract infectionPneumoniaSkin infectionsSinusitis

34

14141413

0

3751


FatiguePeripheral edemaPyrexiaAsthenia

41351814

5313


BruisingRashPetechiae

302511

030


Musculoskeletal painMuscle spasmsArthralgia

371411

100


DyspneaCoughEpistaxis

271911

400


Table 1: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with MCL (N=111) (continued)


All Grades (%)

Grade 3 or 4 (%)


Decreased appetiteDehydration

2112

24


DizzinessHeadache

1413

00

Table 2: Treatment-Emergent* Hematologic Laboratory Abnormalities in Patients with MCL (N=111)

Percent of Patients (N=111)All Grades

(%)Grade 3 or 4

(%)Platelets Decreased 57 17Neutrophils Decreased 47 29Hemoglobin Decreased 41 9

* Based on laboratory measurements and adverse reactions

Ten patients (9%) discontinued treatment due to adverse reactions in the trial (N=111). The most frequent adverse reaction leading to treatment discontinuation was subdural hematoma (1.8%). Adverse reactions leading to dose reduction occurred in 14% of patients.Patients with MCL who develop lymphocytosis greater than 400,000/mcL have developed intracranial hemorrhage, lethargy, gait instability, and headache. However, some of these cases were in the setting of disease progression.Forty percent of patients had elevated uric acid levels on study including 13% with values above 10 mg/dL. Adverse reaction of hyperuricemia was reported for 15% of patients.Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: The data described below reflect exposure in one single-arm, open-label clinical trial (Study 1102) and three randomized controlled clinical trials (RESONATE, RESONATE-2, and HELIOS) in patients with CLL/SLL (n=1278 total and n=668 patients exposed to IMBRUVICA). Study 1102 included 51 patients with previously treated CLL/SLL, RESONATE included 391 randomized patients with previously treated CLL or SLL who received single agent IMBRUVICA or ofatumumab, RESONATE-2 included 269 randomized patients 65 years or older with treatment naïve-CLL or SLL who received single agent IMBRUVICA or chlorambucil, and HELIOS included 578 randomized patients with previously treated CLL or SLL who received IMBRUVICA in combination with bendamustine and rituximab or placebo in combination with bendamustine and rituximab. The most commonly occurring adverse reactions in Studies 1102, RESONATE, RESONATE-2, and HELIOS in patients with CLL/SLL receiving IMBRUVICA (≥ 20%) were neutropenia, thrombocytopenia, anemia, diarrhea, musculoskeletal pain, nausea, rash, bruising, fatigue, pyrexia and hemorrhage. Four to 10 percent of patients receiving IMBRUVICA in Studies 1102, RESONATE, RESONATE-2, and HELIOS discontinued treatment due to adverse reactions. These included pneumonia, hemorrhage, atrial fibrillation, rash and neutropenia (1% each). Adverse reactions leading to dose reduction occurred in approximately 6% of patients.Study 1102: Adverse reactions and laboratory abnormalities from the CLL/SLL trial (N=51) using single agent IMBRUVICA 420 mg daily in patients with previously treated CLL/SLL occurring at a rate of ≥ 10% with a median duration of treatment of 15.6 months are presented in Tables 3 and 4.

Table 3: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with CLL/SLL (N=51) in Study 1102


All Grades

(%)

Grade 3 or 4 (%)


DiarrheaConstipationNauseaStomatitisVomitingAbdominal painDyspepsia

59222020181412

4220200


Upper respiratory tract infectionSinusitisSkin infectionPneumoniaUrinary tract infection

47221612

12

266

10

2

Table 3: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with CLL/SLL (N=51) in Study 1102 (continued)


All Grades

(%)

Grade 3 or 4 (%)


FatiguePyrexia Peripheral edemaAstheniaChills

3324221412

62060


Bruising Rash Petechiae

512516

200


CoughOropharyngeal painDyspnea

221412

000


Musculoskeletal painArthralgiaMuscle spasms

252418

602


DizzinessHeadache

2018

02


Decreased appetite 16 2

Neoplasms benign, malignant, unspecified

Second malignancies*

12* 0

Vascular disorders Hypertension 16 8* One patient death due to histiocytic sarcoma.

Table 4: Treatment-Emergent* Hematologic Laboratory Abnormalities in Patients with CLL/SLL (N=51) in Study 1102



* Based on laboratory measurements per IWCLL criteria and adverse reactions.

RESONATE: Adverse reactions and laboratory abnormalities described below in Tables 5 and 6 reflect exposure to IMBRUVICA with a median duration of 8.6 months and exposure to ofatumumab with a median of 5.3 months in RESONATE in patients with previously treated CLL/SLL.


with CLL/SLL in RESONATE


IMBRUVICA(N=195)

Ofatumumab(N=191)

All Grades(%)

Grade 3 or 4(%)

All Grades(%)

Grade 3 or 4(%)


Diarrhea 48 4 18 2Nausea 26 2 18 0Stomatitis* 17 1 6 1Constipation 15 0 9 0Vomiting 14 0 6 1


Pyrexia 24 2 15 1Infections and infestations

Upper respiratory tract infection 16 1 11 2Pneumonia* 15 10 13 9Sinusitis* 11 1 6 0Urinary tract infection 10 4 5 1


Rash* 24 3 13 0Petechiae 14 0 1 0Bruising* 12 0 1 0

B:11.125 in

T:10.875 inT:8.125 in

S:9.875 inS:7.25 in

T:8.125 in

S:7.25 in

B:8.375 in




67, 95, 4, 16 =


2, 38, 100, 0 =

50, 0, 100, 0 =

96, 0, 30, 45 =

IMBRUVICA® (ibrutinib) capsules IMBRUVICA® (ibrutinib) capsules


with CLL/SLL in RESONATE (continued)


IMBRUVICA(N=195)

Ofatumumab(N=191)

All Grades(%)

Grade 3 or 4(%)

All Grades(%)

Grade 3 or 4(%)


Musculoskeletal Pain*

28 2 18 1

Arthralgia 17 1 7 0Nervous system disorders

Headache 14 1 6 0Dizziness 11 0 5 0

Injury, poisoning and procedural complications

Contusion 11 0 3 0Eye disorders

Vision blurred 10 0 3 0

Subjects with multiple events for a given ADR term are counted once only for each ADR term. The body system and individual ADR terms are sorted in descending frequency order in the IMBRUVICA arm.* Includes multiple ADR terms

Table 6: Treatment-Emergent Hematologic Laboratory Abnormalities in Patients with CLL/SLL in RESONATE

IMBRUVICA(N=195)

Ofatumumab(N=191)

All Grades

(%)

Grade 3 or 4(%)

All Grades

(%)

Grade 3 or 4(%)

Neutrophils Decreased 51 23 57 26Platelets Decreased 52 5 45 10Hemoglobin Decreased 36 0 21 0

RESONATE-2: Adverse reactions described below in Table 7 reflect exposure to IMBRUVICA with a median duration of 17.4 months. The median exposure to chlorambucil was 7.1 months in RESONATE-2.


with CLL/SLL in RESONATE-2


IMBRUVICA(N=135)

Chlorambucil(N=132)

All Grades

(%)

Grade 3 or 4(%)

All Grades

(%)

Grade 3 or 4(%)


Diarrhea 42 4 17 0Stomatitis* 14 1 4 1


Musculoskeletal pain*

36 4 20 0

Arthralgia 16 1 7 1Muscle spasms 11 0 5 0

Eye DisordersDry eye 17 0 5 0Lacrimation increased

13 0 6 0

Vision blurred 13 0 8 0Visual acuity reduced

11 0 2 0


with CLL/SLL in RESONATE-2 (continued)


IMBRUVICA(N=135)

Chlorambucil(N=132)

All Grades

(%)

Grade 3 or 4(%)

All Grades

(%)

Grade 3 or 4(%)


Rash* 21 4 12 2Bruising* 19 0 7 0


Skin infection* 15 2 3 1Pneumonia* 14 8 7 4Urinary tract infections

10 1 8 1


Cough 22 0 15 0General disorders and administration site conditions

Peripheral edema 19 1 9 0Pyrexia 17 0 14 2

Vascular DisordersHypertension* 14 4 1 0

Nervous System Disorders

Headache 12 1 10 2


HELIOS: Adverse reactions described below in Table 8 reflect exposure to IMBRUVICA + BR with a median duration of 14.7 months and exposure to placebo + BR with a median of 12.8 months in HELIOS in patients with previously treated CLL/SLL.

Table 8: Adverse Reactions Reported in at Least 10% of Patients and at Least 2% Greater in the IMBRUVICA Arm in Patients

with CLL/SLL in HELIOS


Ibrutinib + BR(N=287)

Placebo + BR(N=287)

All Grades(%)

Grade 3 or 4(%)

All Grades(%)

Grade 3 or 4(%)

Blood and lymphatic system disorders

Neutropenia* 66 61 60 55Thrombocytopenia* 34 16 26 16


Rash* 32 4 25 1Bruising* 20 <1 8 <1


Diarrhea 36 2 23 1Abdominal Pain 12 1 8 <1



29 2 20 0

Muscle spasms 12 <1 5 0



with CLL/SLL in Study 4 (continued)



Placebo + BR(N=287)

All Grades(%)

Grade 3 or 4(%)

All Grades(%)

Grade 3 or 4(%)


Pyrexia 25 4 22 2Vascular Disorders

Hemorrhage* 19 2 9 1Hypertension* 11 5 5 2


Bronchitis 13 2 10 3Skin infection* 10 3 6 2


Hyperuricemia 10 2 6 0The body system and individual ADR terms are sorted in descending frequency order in the IMBRUVICA arm. * Includes multiple ADR terms <1 used for frequency above 0 and below 0.5%

Atrial fibrillation of any grade occurred in 7% of patients treated with IMBRUVICA + BR and 2% of patients treated with placebo + BR. The frequency of Grade 3 and 4 atrial fibrillation was 3% in patients treated with IMBRUVICA + BR and 1% in patients treated with placebo +BR.Waldenström’s Macroglobulinemia and Marginal Zone Lymphoma: The data described below reflect exposure to IMBRUVICA in open-label clinical trials that included 63 patients with previously treated WM (Study 1118) and 63 patients with previously treated MZL (Study 1121).The most commonly occurring adverse reactions in Studies 1118 and 1121 (≥ 20%) were thrombocytopenia, diarrhea, neutropenia, fatigue, bruising, hemorrhage, anemia, rash, musculoskeletal pain, and nausea.Nine percent of patients receiving IMBRUVICA across Studies 1118 and 1121 discontinued treatment due to adverse reactions. The most common adverse reactions leading to discontinuation were interstitial lung disease, diarrhea and rash. Adverse reactions leading to dose reduction occurred in 10% of patients.Study 1118: Adverse reactions and laboratory abnormalities described below in Tables 9 and 10 reflect exposure to IMBRUVICA with a median duration of 11.7 months in Study 1118.

Table 9: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with WM in Study 1118 (N=63)


All Grades

(%)

Grade 3 or 4 (%)


DiarrheaNauseaStomatitis*Gastroesophageal reflux disease

372116

13

000

0Skin and subcutaneous tissue disorders

Rash*Bruising*Pruritus

221611

000

General disorders and administrative site conditions

Fatigue 21 0


Muscle spasms Arthropathy

2113

00


Upper respiratory tract infectionSinusitisPneumonia*Skin infection*

19191414

0062

Table 9: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with WM in Study 1118 (N=63) (continued)


All Grades

(%)

Grade 3 or 4 (%)


EpistaxisCough

1913

00


DizzinessHeadache

1413

00

Neoplasms benign, malignant, and unspecified (including cysts and polyps)

Skin cancer* 11 0

The body system and individual ADR preferred terms are sorted in descending frequency order.* Includes multiple ADR terms.

Table 10: Treatment-Emergent Hematologic Laboratory Abnormalities in Patients with WM in Study 1118 (N=63)



Study 1121: Adverse reactions and laboratory abnormalities described below in Tables 11 and 12 reflect exposure to IMBRUVICA with a median duration of 11.6 months in Study 1121.

Table 11: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with MZL in Study 1121 (N=63)

Body System Adverse Reaction All Grades

(%)

Grade 3 or 4 (%)


DiarrheaNauseaDyspepsiaStomatitis*Abdominal painConstipationAbdominal pain UpperVomiting

4325191716141311

50022002


FatiguePeripheral edemaPyrexia

442417

622


Bruising *Rash*Pruritus

412914

050


Musculoskeletal pain*ArthralgiaMuscle spasms

402419

323


Upper respiratory tract infectionSinusitis*BronchitisPneumonia*

21191111

000

10Metabolism and nutrition disorders

Decreased appetiteHyperuricemiaHypoalbuminemiaHypokalemia

16161413

2000

Vascular Disorders Hemorrhage*Hypertension*

3014

05


CoughDyspnea

2221

22


DizzinessHeadache

1913

00

Psychiatric disorders Anxiety 16 2The body system and individual ADR preferred terms are sorted in descending frequency order.* Includes multiple ADR terms.

B:11.125 in

T:10.875 in

T:8.125 in

S:9.875 in

S:7.25 in

T:8.125 in

S:7.25 in

B:8.375 in




67, 95, 4, 16 =


2, 38, 100, 0 =

50, 0, 100, 0 =

96, 0, 30, 45 =



with CLL/SLL in RESONATE (continued)


IMBRUVICA(N=195)

Ofatumumab(N=191)

All Grades(%)

Grade 3 or 4(%)

All Grades(%)

Grade 3 or 4(%)


Musculoskeletal Pain*

28 2 18 1

Arthralgia 17 1 7 0Nervous system disorders

Headache 14 1 6 0Dizziness 11 0 5 0


Contusion 11 0 3 0Eye disorders

Vision blurred 10 0 3 0


Table 6: Treatment-Emergent Hematologic Laboratory Abnormalities in Patients with CLL/SLL in RESONATE

IMBRUVICA(N=195)

Ofatumumab(N=191)

All Grades

(%)

Grade 3 or 4(%)

All Grades

(%)

Grade 3 or 4(%)

Neutrophils Decreased 51 23 57 26Platelets Decreased 52 5 45 10Hemoglobin Decreased 36 0 21 0

RESONATE-2: Adverse reactions described below in Table 7 reflect exposure to IMBRUVICA with a median duration of 17.4 months. The median exposure to chlorambucil was 7.1 months in RESONATE-2.


with CLL/SLL in RESONATE-2


IMBRUVICA(N=135)

Chlorambucil(N=132)

All Grades

(%)

Grade 3 or 4(%)

All Grades

(%)

Grade 3 or 4(%)


Diarrhea 42 4 17 0Stomatitis* 14 1 4 1



36 4 20 0

Arthralgia 16 1 7 1Muscle spasms 11 0 5 0

Eye DisordersDry eye 17 0 5 0Lacrimation increased

13 0 6 0

Vision blurred 13 0 8 0Visual acuity reduced

11 0 2 0


with CLL/SLL in RESONATE-2 (continued)


IMBRUVICA(N=135)

Chlorambucil(N=132)

All Grades

(%)

Grade 3 or 4(%)

All Grades

(%)

Grade 3 or 4(%)


Rash* 21 4 12 2Bruising* 19 0 7 0


Skin infection* 15 2 3 1Pneumonia* 14 8 7 4Urinary tract infections

10 1 8 1


Cough 22 0 15 0General disorders and administration site conditions

Peripheral edema 19 1 9 0Pyrexia 17 0 14 2

Vascular DisordersHypertension* 14 4 1 0

Nervous System Disorders

Headache 12 1 10 2


HELIOS: Adverse reactions described below in Table 8 reflect exposure to IMBRUVICA + BR with a median duration of 14.7 months and exposure to placebo + BR with a median of 12.8 months in HELIOS in patients with previously treated CLL/SLL.


with CLL/SLL in HELIOS



Placebo + BR(N=287)

All Grades(%)

Grade 3 or 4(%)

All Grades(%)

Grade 3 or 4(%)

Blood and lymphatic system disorders

Neutropenia* 66 61 60 55Thrombocytopenia* 34 16 26 16


Rash* 32 4 25 1Bruising* 20 <1 8 <1


Diarrhea 36 2 23 1Abdominal Pain 12 1 8 <1



29 2 20 0

Muscle spasms 12 <1 5 0



with CLL/SLL in Study 4 (continued)



Placebo + BR(N=287)

All Grades(%)

Grade 3 or 4(%)

All Grades(%)

Grade 3 or 4(%)


Pyrexia 25 4 22 2Vascular Disorders

Hemorrhage* 19 2 9 1Hypertension* 11 5 5 2


Bronchitis 13 2 10 3Skin infection* 10 3 6 2


Hyperuricemia 10 2 6 0The body system and individual ADR terms are sorted in descending frequency order in the IMBRUVICA arm. * Includes multiple ADR terms <1 used for frequency above 0 and below 0.5%

Atrial fibrillation of any grade occurred in 7% of patients treated with IMBRUVICA + BR and 2% of patients treated with placebo + BR. The frequency of Grade 3 and 4 atrial fibrillation was 3% in patients treated with IMBRUVICA + BR and 1% in patients treated with placebo +BR.Waldenström’s Macroglobulinemia and Marginal Zone Lymphoma: The data described below reflect exposure to IMBRUVICA in open-label clinical trials that included 63 patients with previously treated WM (Study 1118) and 63 patients with previously treated MZL (Study 1121).The most commonly occurring adverse reactions in Studies 1118 and 1121 (≥ 20%) were thrombocytopenia, diarrhea, neutropenia, fatigue, bruising, hemorrhage, anemia, rash, musculoskeletal pain, and nausea.Nine percent of patients receiving IMBRUVICA across Studies 1118 and 1121 discontinued treatment due to adverse reactions. The most common adverse reactions leading to discontinuation were interstitial lung disease, diarrhea and rash. Adverse reactions leading to dose reduction occurred in 10% of patients.Study 1118: Adverse reactions and laboratory abnormalities described below in Tables 9 and 10 reflect exposure to IMBRUVICA with a median duration of 11.7 months in Study 1118.

Table 9: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with WM in Study 1118 (N=63)


All Grades

(%)

Grade 3 or 4 (%)


DiarrheaNauseaStomatitis*Gastroesophageal reflux disease

372116

13

000

0Skin and subcutaneous tissue disorders

Rash*Bruising*Pruritus

221611

000


Fatigue 21 0


Muscle spasms Arthropathy

2113

00


Upper respiratory tract infectionSinusitisPneumonia*Skin infection*

19191414

0062

Table 9: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with WM in Study 1118 (N=63) (continued)


All Grades

(%)

Grade 3 or 4 (%)


EpistaxisCough

1913

00


DizzinessHeadache

1413

00

Neoplasms benign, malignant, and unspecified (including cysts and polyps)

Skin cancer* 11 0

The body system and individual ADR preferred terms are sorted in descending frequency order.* Includes multiple ADR terms.

Table 10: Treatment-Emergent Hematologic Laboratory Abnormalities in Patients with WM in Study 1118 (N=63)



Study 1121: Adverse reactions and laboratory abnormalities described below in Tables 11 and 12 reflect exposure to IMBRUVICA with a median duration of 11.6 months in Study 1121.

Table 11: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with MZL in Study 1121 (N=63)

Body System Adverse Reaction All Grades

(%)

Grade 3 or 4 (%)


DiarrheaNauseaDyspepsiaStomatitis*Abdominal painConstipationAbdominal pain UpperVomiting

4325191716141311

50022002


FatiguePeripheral edemaPyrexia

442417

622


Bruising *Rash*Pruritus

412914

050


Musculoskeletal pain*ArthralgiaMuscle spasms

402419

323


Upper respiratory tract infectionSinusitis*BronchitisPneumonia*

21191111

000

10Metabolism and nutrition disorders

Decreased appetiteHyperuricemiaHypoalbuminemiaHypokalemia

16161413

2000

Vascular Disorders Hemorrhage*Hypertension*

3014

05


CoughDyspnea

2221

22


DizzinessHeadache

1913

00

Psychiatric disorders Anxiety 16 2The body system and individual ADR preferred terms are sorted in descending frequency order.* Includes multiple ADR terms.

B:11.125 in

T:10.875 inT:8.125 in

S:9.875 inS:7.25 in

T:8.125 in

S:7.25 in

B:8.375 in




67, 95, 4, 16 =


2, 38, 100, 0 =

50, 0, 100, 0 =

96, 0, 30, 45 =

IMBRUVICA® (ibrutinib) capsules

Table 12: Treatment-Emergent Hematologic Laboratory Abnormalities in Patients with MZL in Study 1121 (N=63)


Platelets Decreased 49 6Hemoglobin Decreased 43 13Neutrophils Decreased 22 13

Chronic Graft versus Host Disease: The data described below reflect exposure to IMBRUVICA in an open-label clinical trial (Study 1129) that included 42 patients with cGVHD after failure of first line corticosteroid therapy and required additional therapy.The most commonly occurring adverse reactions in the cGVHD trial (≥ 20%) were fatigue, bruising, diarrhea, thrombocytopenia, stomatitis, muscle spasms, nausea, hemorrhage, anemia, and pneumonia. Atrial fibrillation occurred in one patient (2%) which was Grade 3.Twenty-four percent of patients receiving IMBRUVICA in the cGVHD trial discontinued treatment due to adverse reactions. The most common adverse reactions leading to discontinuation were fatigue and pneumonia. Adverse reactions leading to dose reduction occurred in 26% of patients.Adverse reactions and laboratory abnormalities described below in Tables 13 and 14 reflect exposure to IMBRUVICA with a median duration of 4.4 months in the cGVHD trial.

Table 13: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with cGVHD (N=42)


All Grades

(%)

Grade 3 or 4 (%)


FatiguePyrexiaEdema peripheral

571712

1250


Bruising*Rash*

4012

00


DiarrheaStomatitis*NauseaConstipation

36292612

10200


Muscle spasmsMusculoskeletal pain*

29

14

2

5Vascular disorders Hemorrhage* 26 0Infections and infestations

Pneumonia*Upper respiratory tract infectionSepsis*

21

1910

10

010


Headache 17 5


Fall 17 0


CoughDyspnea

1412

02


Hypokalemia 12 7

The system organ class and individual ADR preferred terms are sorted in descending frequency order.* Includes multiple ADR terms.

Table 14: Treatment-Emergent Hematologic Laboratory Abnormalities in Patients with cGVHD (N=42)



Additional Important Adverse Reactions: Diarrhea: Diarrhea of any grade occurred at a rate of 43% (range, 36% to 59%) of patients treated with IMBRUVICA. Grade 2 diarrhea occurred in 9% (range, 3% to 14%) and Grade 3 in 3% (range, 0 to 5%) of patients treated with IMBRUVICA. The median time to first onset of any grade diarrhea was 10 days (range, 0 to 627), of Grade 2 was 39 days (range, 1 to 719) and of Grade 3 was 74 days (range, 3 to 627). Of the

patients who reported diarrhea, 82% had complete resolution, 1% had partial improvement and 17% had no reported improvement at time of analysis. The median time from onset to resolution or improvement of any grade diarrhea was 5 days (range, 1 to 418), and was similar for Grades 2 and 3. Less than 1% of patients discontinued IMBRUVICA due to diarrhea.Visual Disturbance: Blurred vision and decreased visual acuity of any grade occurred in 10% of patients treated with IMBRUVICA (9% Grade 1, 2% Grade 2). The median time to first onset was 85 days (range, 1 to 414 days). Of the patients with visual disturbance, 61% had complete resolution and 38% had no reported improvement at time of analysis. The median time from onset to resolution or improvement was 29 days (range, 1 to 335 days). Postmarketing Experience: The following adverse reactions have been identified during post-approval use of IMBRUVICA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Hepatobiliary disorders: hepatic failure• Respiratory disorders: interstitial lung disease• Metabolic and nutrition disorders: tumor lysis syndrome [see Warnings

& Precautions]• Immune system disorders: anaphylactic shock, angioedema, urticaria• Skin and subcutaneous tissue disorders: Stevens-Johnson Syndrome

(SJS), onychoclasis• Infections: hepatitis B reactivation

DRUG INTERACTIONSEffect of CYP3A Inhibitors on Ibrutinib: The coadministration of IMBRUVICA with a strong or moderate CYP3A inhibitor may increase ibrutinib plasma concentrations [see Clinical Pharmacology (12.3) in Full Prescribing Information]. Increased ibrutinib concentrations may increase the risk of drug-related toxicity.Examplesa of strong CYP3A inhibitors include: boceprevir, clarithromycin, cobicistat conivaptan, danoprevir and ritonavir, diltiazem, elvitegravir and ritonavir, idelalisib, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, nefazodone, nelfinavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), ritonavir, saquinavir and ritonavir, tipranavir and ritonavir, and troleandomycin.Examplesa of moderate CYP3A inhibitors include: aprepitant, cimetidine, ciprofloxacin, clotrimazole, crizotinib, cyclosporine, dronedarone, erythromycin, fluconazole, fluvoxamine, imatinib, tofisopam, and verapamil.Avoid grapefruit and Seville oranges during IMBRUVICA treatment, as these contain strong or moderate inhibitors of CYP3A.Patients with B-cell Malignancies: Posaconazole: Reduce IMBRUVICA dose to 140 mg once daily during coadministration with posaconazole at doses of no more than 200 mg BID [see Dosage and Administration (2.4) in Full Prescribing Information]. Avoid the coadministration of IMBRUVICA with posaconazole at doses of greater than 200 mg BID.Voriconazole: Reduce IMBRUVICA dose to 140 mg once daily during coadministration with any dose of voriconazole [see Dosage and Administration (2.4) in Full Prescribing Information].Other Strong Inhibitors: Avoid concomitant administration of IMBRUVICA with other strong CYP3A inhibitors. Alternatively, interrupt IMBRUVICA therapy during the duration of strong CYP3A inhibitors if the inhibitor will be used short-term (such as anti-infectives for seven days or less) [see Dosage and Administration (2.4) in Full Prescribing Information].Moderate Inhibitors: Reduce IMBRUVICA dose to 140 mg once daily during coadministration with any moderate CYP3A inhibitor [see Dosage and Administration (2.4) in Full Prescribing Information].Monitor patients taking concomitant strong or moderate CYP3A inhibitors more frequently for adverse reactions of IMBRUVICA.Patients with Chronic Graft versus Host Disease: Moderate CYP3A Inhibitor: Modify the dose based on adverse reactions [see Dosage and Administration (2.3) in Full Prescribing Information] for patients coadministered IMBRUVICA with any moderate CYP3A inhibitor.Strong CYP3A Inhibitors: Reduce IMBRUVICA dose to 280 mg once daily for patients coadministered IMBRUVICA with

• posaconazole immediate-release tablet 200 mg BID or• posaconazole delayed-release tablet 300 mg QD or• voriconazole any dose

Modify the dose based on adverse reactions [see Dosage and Administration (2.3) in Full Prescribing Information]Avoid concomitant administration of IMBRUVICA with posaconazole at higher doses and other strong CYP3A inhibitors. If these CYP3A inhibitors will be used short-term (such as anti-infectives for seven days or less), interrupt IMBRUVICA therapy during the duration of the inhibitor [see Dosage and Administration (2.4) in Full Prescribing Information].


Effect of CYP3A Inducers on Ibrutinib: The coadministration of IMBRUVICA with strong CYP3A inducers may decrease ibrutinib concentrations. Avoid coadministration with strong CYP3A inducers [see Clinical Pharmacology (12.3) in Full Prescribing Information]. Examplesa of strong CYP3A inducers include: carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, and St. John’s wortb.a These examples are a guide and not considered a comprehensive list of all

possible drugs that may fit this category. The healthcare provider should consult appropriate references for comprehensive information.

b The induction potency of St. John’s wort may vary widely based on preparation.

USE IN SPECIFIC POPULATIONSPregnancy: Risk Summary: IMBRUVICA, a kinase inhibitor, can cause fetal harm based on findings from animal studies. There are no available data on IMBRUVICA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, administration of ibrutinib to pregnant rats and rabbits during the period of organogenesis at exposures up to 2-20 times the clinical doses of 420-560 mg daily produced embryofetal toxicity including structural abnormalities (see Animal Data). If IMBRUVICA is used during pregnancy or if the patient becomes pregnant while taking IMBRUVICA, the patient should be apprised of the potential hazard to the fetus.All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.Animal Data: Ibrutinib was administered orally to pregnant rats during the period of organogenesis at doses of 10, 40 and 80 mg/kg/day. Ibrutinib at a dose of 80 mg/kg/day was associated with visceral malformations (heart and major vessels) and increased resorptions and post-implantation loss. The dose of 80 mg/kg/day in rats is approximately 14 times the exposure (AUC) in patients with MCL or MZL and 20 times the exposure in patients with CLL/SLL or WM administered the dose of 560 mg daily and 420 mg daily, respectively. Ibrutinib at doses of 40 mg/kg/day or greater was associated with decreased fetal weights. The dose of 40 mg/kg/day in rats is approximately 6 times the exposure (AUC) in patients with MCL administered the dose of 560 mg daily.Ibrutinib was also administered orally to pregnant rabbits during the period of organogenesis at doses of 5, 15, and 45 mg/kg/day. Ibrutinib at a dose of 15 mg/kg/day or greater was associated with skeletal variations (fused sternebrae) and ibrutinib at a dose of 45 mg/kg/day was associated with increased resorptions and post-implantation loss. The dose of 15 mg/kg/day in rabbits is approximately 2.0 times the exposure (AUC) in patients with MCL and 2.8 times the exposure in patients with CLL/SLL or WM administered the dose of 560 and 420 mg daily, respectively. Lactation: Risk Summary: There is no information regarding the presence of ibrutinib or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for IMBRUVICA and any potential adverse effects on the breastfed child from IMBRUVICA or from the underlying maternal condition.Females and Males of Reproductive Potential: Pregnancy Testing: Verify the pregnancy status of females of reproductive potential prior to initiating IMBRUVICA therapy.ContraceptionFemales: Advise females of reproductive potential to avoid pregnancy while taking IMBRUVICA and for up to 1 month after ending treatment. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus.Males: Advise men to avoid fathering a child while receiving IMBRUVICA, and for 1 month following the last dose of IMBRUVICA.Pediatric Use: The safety and effectiveness of IMBRUVICA in pediatric patients has not been established.Geriatric Use: Of the 905 patients in clinical studies of IMBRUVICA, 62% were ≥ 65 years of age, while 21% were ≥75 years of age. No overall differences in effectiveness were observed between younger and older patients. Anemia (all grades) and Grade 3 or higher pneumonia occurred more frequently among older patients treated with IMBRUVICA. Hepatic Impairment: Avoid use of IMBRUVICA in patients with moderate or severe hepatic impairment (Child-Pugh class B and C). The safety of IMBRUVICA has not been evaluated in patients with mild to severe hepatic impairment by Child-Pugh criteria.

Monitor patients for adverse reactions of IMBRUVICA and follow dose modification guidance as needed. [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) in Full Prescribing Information].Plasmapheresis: Management of hyperviscosity in WM patients may include plasmapheresis before and during treatment with IMBRUVICA.Modifications to IMBRUVICA dosing are not required.PATIENT COUNSELING INFORMATIONAdvise the patient to read the FDA-approved patient labeling (Patient Information). • Hemorrhage: Inform patients of the possibility of bleeding, and to report

any signs or symptoms (severe headache, blood in stools or urine, prolonged or uncontrolled bleeding). Inform the patient that IMBRUVICA may need to be interrupted for medical or dental procedures [see Warnings and Precautions].

• Infections: Inform patients of the possibility of serious infection, and to report any signs or symptoms (fever, chills, weakness, confusion) suggestive of infection [see Warnings and Precautions].

• Atrial fibrillation: Counsel patients to report any signs of palpitations, lightheadedness, dizziness, fainting, shortness of breath, and chest discomfort [see Warnings and Precautions].

• Hypertension: Inform patients that high blood pressure has occurred in patients taking IMBRUVICA, which may require treatment with anti-hypertensive therapy [see Warnings and Precautions].

• Second primary malignancies: Inform patients that other malignancies have occurred in patients who have been treated with IMBRUVICA, including skin cancers and other carcinomas [see Warnings and Precautions].

• Tumor lysis syndrome: Inform patients of the potential risk of tumor lysis syndrome and to report any signs and symptoms associated with this event to their healthcare provider for evaluation [see Warnings and Precautions].

• Embryo-fetal toxicity: Advise women of the potential hazard to a fetus and to avoid becoming pregnant during treatment and for 1 month after the last dose of IMBRUVICA [see Warnings and Precautions].

• Inform patients to take IMBRUVICA orally once daily according to their physician’s instructions and that the capsules should be swallowed whole with a glass of water without being opened, broken, or chewed at approximately the same time each day [see Dosage and Administration (2.1) in Full Prescribing Information].

• Advise patients that in the event of a missed daily dose of IMBRUVICA, it should be taken as soon as possible on the same day with a return to the normal schedule the following day. Patients should not take extra capsules to make up the missed dose [see Dosage and Administration (2.6) in Full Prescribing Information].

• Advise patients of the common side effects associated with IMBRUVICA [see Adverse Reactions]. Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION.

• Advise patients to inform their health care providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions].

• Advise patients that they may experience loose stools or diarrhea, and should contact their doctor if their diarrhea persists. Advise patients to maintain adequate hydration [see Adverse Reactions].

Active ingredient made in China.

Distributed and Marketed by:Pharmacyclics LLCSunnyvale, CA USA 94085andMarketed by:Janssen Biotech, Inc.Horsham, PA USA 19044

Patent http://www.imbruvica.comIMBRUVICA® is a registered trademark owned by Pharmacyclics LLC

© Pharmacyclics LLC 2017© Janssen Biotech, Inc. 2017

PRC-03046

B:11.125 in

T:10.875 in

T:8.125 in

S:9.875 in

S:7.25 in

T:8.125 in

S:7.25 in

B:8.375 in




67, 95, 4, 16 =


2, 38, 100, 0 =

50, 0, 100, 0 =

96, 0, 30, 45 =

IMBRUVICA® (ibrutinib) capsules

Table 12: Treatment-Emergent Hematologic Laboratory Abnormalities in Patients with MZL in Study 1121 (N=63)


Platelets Decreased 49 6Hemoglobin Decreased 43 13Neutrophils Decreased 22 13

Chronic Graft versus Host Disease: The data described below reflect exposure to IMBRUVICA in an open-label clinical trial (Study 1129) that included 42 patients with cGVHD after failure of first line corticosteroid therapy and required additional therapy.The most commonly occurring adverse reactions in the cGVHD trial (≥ 20%) were fatigue, bruising, diarrhea, thrombocytopenia, stomatitis, muscle spasms, nausea, hemorrhage, anemia, and pneumonia. Atrial fibrillation occurred in one patient (2%) which was Grade 3.Twenty-four percent of patients receiving IMBRUVICA in the cGVHD trial discontinued treatment due to adverse reactions. The most common adverse reactions leading to discontinuation were fatigue and pneumonia. Adverse reactions leading to dose reduction occurred in 26% of patients.Adverse reactions and laboratory abnormalities described below in Tables 13 and 14 reflect exposure to IMBRUVICA with a median duration of 4.4 months in the cGVHD trial.

Table 13: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with cGVHD (N=42)


All Grades

(%)

Grade 3 or 4 (%)


FatiguePyrexiaEdema peripheral

571712

1250


Bruising*Rash*

4012

00


DiarrheaStomatitis*NauseaConstipation

36292612

10200


Muscle spasmsMusculoskeletal pain*

29

14

2

5Vascular disorders Hemorrhage* 26 0Infections and infestations

Pneumonia*Upper respiratory tract infectionSepsis*

21

1910

10

010


Headache 17 5


Fall 17 0


CoughDyspnea

1412

02


Hypokalemia 12 7

The system organ class and individual ADR preferred terms are sorted in descending frequency order.* Includes multiple ADR terms.

Table 14: Treatment-Emergent Hematologic Laboratory Abnormalities in Patients with cGVHD (N=42)



Additional Important Adverse Reactions: Diarrhea: Diarrhea of any grade occurred at a rate of 43% (range, 36% to 59%) of patients treated with IMBRUVICA. Grade 2 diarrhea occurred in 9% (range, 3% to 14%) and Grade 3 in 3% (range, 0 to 5%) of patients treated with IMBRUVICA. The median time to first onset of any grade diarrhea was 10 days (range, 0 to 627), of Grade 2 was 39 days (range, 1 to 719) and of Grade 3 was 74 days (range, 3 to 627). Of the

patients who reported diarrhea, 82% had complete resolution, 1% had partial improvement and 17% had no reported improvement at time of analysis. The median time from onset to resolution or improvement of any grade diarrhea was 5 days (range, 1 to 418), and was similar for Grades 2 and 3. Less than 1% of patients discontinued IMBRUVICA due to diarrhea.Visual Disturbance: Blurred vision and decreased visual acuity of any grade occurred in 10% of patients treated with IMBRUVICA (9% Grade 1, 2% Grade 2). The median time to first onset was 85 days (range, 1 to 414 days). Of the patients with visual disturbance, 61% had complete resolution and 38% had no reported improvement at time of analysis. The median time from onset to resolution or improvement was 29 days (range, 1 to 335 days). Postmarketing Experience: The following adverse reactions have been identified during post-approval use of IMBRUVICA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Hepatobiliary disorders: hepatic failure• Respiratory disorders: interstitial lung disease• Metabolic and nutrition disorders: tumor lysis syndrome [see Warnings

& Precautions]• Immune system disorders: anaphylactic shock, angioedema, urticaria• Skin and subcutaneous tissue disorders: Stevens-Johnson Syndrome

(SJS), onychoclasis• Infections: hepatitis B reactivation

DRUG INTERACTIONSEffect of CYP3A Inhibitors on Ibrutinib: The coadministration of IMBRUVICA with a strong or moderate CYP3A inhibitor may increase ibrutinib plasma concentrations [see Clinical Pharmacology (12.3) in Full Prescribing Information]. Increased ibrutinib concentrations may increase the risk of drug-related toxicity.Examplesa of strong CYP3A inhibitors include: boceprevir, clarithromycin, cobicistat conivaptan, danoprevir and ritonavir, diltiazem, elvitegravir and ritonavir, idelalisib, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, nefazodone, nelfinavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), ritonavir, saquinavir and ritonavir, tipranavir and ritonavir, and troleandomycin.Examplesa of moderate CYP3A inhibitors include: aprepitant, cimetidine, ciprofloxacin, clotrimazole, crizotinib, cyclosporine, dronedarone, erythromycin, fluconazole, fluvoxamine, imatinib, tofisopam, and verapamil.Avoid grapefruit and Seville oranges during IMBRUVICA treatment, as these contain strong or moderate inhibitors of CYP3A.Patients with B-cell Malignancies: Posaconazole: Reduce IMBRUVICA dose to 140 mg once daily during coadministration with posaconazole at doses of no more than 200 mg BID [see Dosage and Administration (2.4) in Full Prescribing Information]. Avoid the coadministration of IMBRUVICA with posaconazole at doses of greater than 200 mg BID.Voriconazole: Reduce IMBRUVICA dose to 140 mg once daily during coadministration with any dose of voriconazole [see Dosage and Administration (2.4) in Full Prescribing Information].Other Strong Inhibitors: Avoid concomitant administration of IMBRUVICA with other strong CYP3A inhibitors. Alternatively, interrupt IMBRUVICA therapy during the duration of strong CYP3A inhibitors if the inhibitor will be used short-term (such as anti-infectives for seven days or less) [see Dosage and Administration (2.4) in Full Prescribing Information].Moderate Inhibitors: Reduce IMBRUVICA dose to 140 mg once daily during coadministration with any moderate CYP3A inhibitor [see Dosage and Administration (2.4) in Full Prescribing Information].Monitor patients taking concomitant strong or moderate CYP3A inhibitors more frequently for adverse reactions of IMBRUVICA.Patients with Chronic Graft versus Host Disease: Moderate CYP3A Inhibitor: Modify the dose based on adverse reactions [see Dosage and Administration (2.3) in Full Prescribing Information] for patients coadministered IMBRUVICA with any moderate CYP3A inhibitor.Strong CYP3A Inhibitors: Reduce IMBRUVICA dose to 280 mg once daily for patients coadministered IMBRUVICA with

• posaconazole immediate-release tablet 200 mg BID or• posaconazole delayed-release tablet 300 mg QD or• voriconazole any dose

Modify the dose based on adverse reactions [see Dosage and Administration (2.3) in Full Prescribing Information]Avoid concomitant administration of IMBRUVICA with posaconazole at higher doses and other strong CYP3A inhibitors. If these CYP3A inhibitors will be used short-term (such as anti-infectives for seven days or less), interrupt IMBRUVICA therapy during the duration of the inhibitor [see Dosage and Administration (2.4) in Full Prescribing Information].


Effect of CYP3A Inducers on Ibrutinib: The coadministration of IMBRUVICA with strong CYP3A inducers may decrease ibrutinib concentrations. Avoid coadministration with strong CYP3A inducers [see Clinical Pharmacology (12.3) in Full Prescribing Information]. Examplesa of strong CYP3A inducers include: carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, and St. John’s wortb.a These examples are a guide and not considered a comprehensive list of all

possible drugs that may fit this category. The healthcare provider should consult appropriate references for comprehensive information.

b The induction potency of St. John’s wort may vary widely based on preparation.

USE IN SPECIFIC POPULATIONSPregnancy: Risk Summary: IMBRUVICA, a kinase inhibitor, can cause fetal harm based on findings from animal studies. There are no available data on IMBRUVICA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, administration of ibrutinib to pregnant rats and rabbits during the period of organogenesis at exposures up to 2-20 times the clinical doses of 420-560 mg daily produced embryofetal toxicity including structural abnormalities (see Animal Data). If IMBRUVICA is used during pregnancy or if the patient becomes pregnant while taking IMBRUVICA, the patient should be apprised of the potential hazard to the fetus.All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.Animal Data: Ibrutinib was administered orally to pregnant rats during the period of organogenesis at doses of 10, 40 and 80 mg/kg/day. Ibrutinib at a dose of 80 mg/kg/day was associated with visceral malformations (heart and major vessels) and increased resorptions and post-implantation loss. The dose of 80 mg/kg/day in rats is approximately 14 times the exposure (AUC) in patients with MCL or MZL and 20 times the exposure in patients with CLL/SLL or WM administered the dose of 560 mg daily and 420 mg daily, respectively. Ibrutinib at doses of 40 mg/kg/day or greater was associated with decreased fetal weights. The dose of 40 mg/kg/day in rats is approximately 6 times the exposure (AUC) in patients with MCL administered the dose of 560 mg daily.Ibrutinib was also administered orally to pregnant rabbits during the period of organogenesis at doses of 5, 15, and 45 mg/kg/day. Ibrutinib at a dose of 15 mg/kg/day or greater was associated with skeletal variations (fused sternebrae) and ibrutinib at a dose of 45 mg/kg/day was associated with increased resorptions and post-implantation loss. The dose of 15 mg/kg/day in rabbits is approximately 2.0 times the exposure (AUC) in patients with MCL and 2.8 times the exposure in patients with CLL/SLL or WM administered the dose of 560 and 420 mg daily, respectively. Lactation: Risk Summary: There is no information regarding the presence of ibrutinib or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for IMBRUVICA and any potential adverse effects on the breastfed child from IMBRUVICA or from the underlying maternal condition.Females and Males of Reproductive Potential: Pregnancy Testing: Verify the pregnancy status of females of reproductive potential prior to initiating IMBRUVICA therapy.ContraceptionFemales: Advise females of reproductive potential to avoid pregnancy while taking IMBRUVICA and for up to 1 month after ending treatment. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus.Males: Advise men to avoid fathering a child while receiving IMBRUVICA, and for 1 month following the last dose of IMBRUVICA.Pediatric Use: The safety and effectiveness of IMBRUVICA in pediatric patients has not been established.Geriatric Use: Of the 905 patients in clinical studies of IMBRUVICA, 62% were ≥ 65 years of age, while 21% were ≥75 years of age. No overall differences in effectiveness were observed between younger and older patients. Anemia (all grades) and Grade 3 or higher pneumonia occurred more frequently among older patients treated with IMBRUVICA. Hepatic Impairment: Avoid use of IMBRUVICA in patients with moderate or severe hepatic impairment (Child-Pugh class B and C). The safety of IMBRUVICA has not been evaluated in patients with mild to severe hepatic impairment by Child-Pugh criteria.

Monitor patients for adverse reactions of IMBRUVICA and follow dose modification guidance as needed. [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) in Full Prescribing Information].Plasmapheresis: Management of hyperviscosity in WM patients may include plasmapheresis before and during treatment with IMBRUVICA.Modifications to IMBRUVICA dosing are not required.PATIENT COUNSELING INFORMATIONAdvise the patient to read the FDA-approved patient labeling (Patient Information). • Hemorrhage: Inform patients of the possibility of bleeding, and to report

any signs or symptoms (severe headache, blood in stools or urine, prolonged or uncontrolled bleeding). Inform the patient that IMBRUVICA may need to be interrupted for medical or dental procedures [see Warnings and Precautions].

• Infections: Inform patients of the possibility of serious infection, and to report any signs or symptoms (fever, chills, weakness, confusion) suggestive of infection [see Warnings and Precautions].

• Atrial fibrillation: Counsel patients to report any signs of palpitations, lightheadedness, dizziness, fainting, shortness of breath, and chest discomfort [see Warnings and Precautions].

• Hypertension: Inform patients that high blood pressure has occurred in patients taking IMBRUVICA, which may require treatment with anti-hypertensive therapy [see Warnings and Precautions].

• Second primary malignancies: Inform patients that other malignancies have occurred in patients who have been treated with IMBRUVICA, including skin cancers and other carcinomas [see Warnings and Precautions].

• Tumor lysis syndrome: Inform patients of the potential risk of tumor lysis syndrome and to report any signs and symptoms associated with this event to their healthcare provider for evaluation [see Warnings and Precautions].

• Embryo-fetal toxicity: Advise women of the potential hazard to a fetus and to avoid becoming pregnant during treatment and for 1 month after the last dose of IMBRUVICA [see Warnings and Precautions].

• Inform patients to take IMBRUVICA orally once daily according to their physician’s instructions and that the capsules should be swallowed whole with a glass of water without being opened, broken, or chewed at approximately the same time each day [see Dosage and Administration (2.1) in Full Prescribing Information].

• Advise patients that in the event of a missed daily dose of IMBRUVICA, it should be taken as soon as possible on the same day with a return to the normal schedule the following day. Patients should not take extra capsules to make up the missed dose [see Dosage and Administration (2.6) in Full Prescribing Information].

• Advise patients of the common side effects associated with IMBRUVICA [see Adverse Reactions]. Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION.

• Advise patients to inform their health care providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions].

• Advise patients that they may experience loose stools or diarrhea, and should contact their doctor if their diarrhea persists. Advise patients to maintain adequate hydration [see Adverse Reactions].

Active ingredient made in China.

Distributed and Marketed by:Pharmacyclics LLCSunnyvale, CA USA 94085andMarketed by:Janssen Biotech, Inc.Horsham, PA USA 19044

Patent http://www.imbruvica.comIMBRUVICA® is a registered trademark owned by Pharmacyclics LLC

© Pharmacyclics LLC 2017© Janssen Biotech, Inc. 2017

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CQC leARninG COllAbORATive

Groups interested in developing advanced care management programs are participating in California Quality Collaborative’s (CQC) “Building Care Solutions for Older adults With Complex Needs” learning collaborative. participants explore the use of home visits to support medically complex patients, using a range of clinical and non-clinical staff. typically, non-licensed staff are paired with lower acuity patients, while physicians and nurses are matched with the highest severity patients.

home visits using medical assistants have been effective for such tasks as medication compliance reviews and chronic disease monitoring, supported by phone reports to clinical nurse supervisors. One participating group documented a 56 percent reduction in hospital admissions and a 28 percent reduction in emergency room visits for patients in the program.

OveRCOMinG CHAllenGeS

In-home care programs face substantial challenges. It starts with having to address patients’ resistance to having an unknown provider see them in the home. this can be overcome by having the patient’s personal physician endorse the program. patients who try in-home care often come to love it, as do their physicians.

perhaps the biggest challenge is maintaining adequate staffing—finding individuals with the clinical competencies and passion to work in a field environment. Improving provider efficiency by finding

better telemedicine solutions may be critical in extending programs’ reach.

providing appropriate and necessary care to those with significant behavioral issues—especially when complicated by homelessness and substance abuse—can be an overwhelming problem.

to make more effective use of limited valuable resources, groups also must better identify and risk-stratify at-risk populations. this will require enhanced use of claims and referral data, as well as sophisticated predictive modeling tools that incorporate social determinants of health. extending services to the growing number of aCO patients, despite data and attribution delays, will be an additional burden on resources.

Finally, many groups providing in-home care believe they have shown a financial return on their investments by reducing emergency department visits and hospital readmission rates and improving risk adjustment factor (raF) score-generated Medicare advantage revenue. however, better methods to track clinical and financial outcomes are essential to support expansion of these costly programs.

the growth of the senior population—especially the very elderly and increasing numbers of disabled americans—will drive the need to expand and improve in-home care services. hopefully, utilization of new technologies will expand the reach of this care. It is likely that risk-managing groups and healthcare systems will lead the development of in-home care programs as part of building a more clinically and economically effective 21st century healthcare system. o

Value-Based Contracting....continued from page 13

may not directly bill for care coordination services—including home visits—performed by Ipa staff.

an Ipa as a managed care organization may subcontract to provide tCM services. Such services, as well as telephone case management, may be deemed the “practice of nursing” under state regulation; the licensed nurse and employing Ipa may incur liability excluded from standard managed care insurance. If liability insurance is not available to the Ipa, one possible approach is to require individual liability protection—naming the Ipa as an “also insured”—with reimbursement provided for the premium. legal consultation is advised. o

1Sarah Ruiz, Lynne Page Snyder, Christina Rotondo, Caitlin Cross-Barnet, Erin Murphy Colligan, and Katherine Gluriceo, “Innovative Home Visit Models Associated with Reductions in Costs, Hospitalizations, and Emergency Department Use,” Health Affairs 36, no 3 (2017): 425-432, doi:10.0377/hithaf.2016.13052Soeren Mattke, Dan Han, Asa Wilks, and Elizabeth Sloss, “Medicare Home Visit Program Associated with Fewer Hospital and Nursing Home Admissions, Increased Office Visits,” Health Affairs 34, no 12 (2015):2138-2146, hoi:10.1377/hithaff.2015.05833Institute for Healthcare Improvement/National Patient Safety Foundation, prepared by Westat. “Patient Safety in the Home: Assessment of Issues, Challenges, and Opportunities.” 4MedPac Report to the Congress, Medicare Payment Policy, March 2017, Chapter 9: “Home Health Care Services: Assessing payment adequacy and updating payments.” 229-253.5Nengliang Yao, Christine Ritchie, Fabian Camacho, and Bruce Leff, “Geographic Concentration of Home-Based Medical Care Providers,” Health Affairs 35, no 8 (2016):1404-1409, doi:10.1377/hrhD2015.14376Personal communications with certified HHA operator and with the PSW Director of Care Management7Pershing Yookley & Associates, PC (PYA) Leadership Briefing. “Providing and Billing Medicare for Transitional Care Management.” November 2014. http://www.pyapc.com/resources/collateral/white-papers/TCM-whitepaper-PYA.pdf

In-Home Care...continued from page 15

A new Model of Home-based CareBY NeIl a. SOlOMON, MD, aND JOrGe WeINGarteN, MD

homebound patients challenge clinicians because the healthcare delivery system is designed to see patients in physicians’ offices and clinics. homebound patients are unable to access needed services in the traditional way, and thus are at risk of higher morbidity. It is the medical and social circumstances that prevent them from leaving their home to travel to sites of care that put them at high risk in the first place. the consequence is increased admissions and

emergency department visits, resulting in decreased quality of care and increased medical expense.

today, approximately 5 to 6 percent of americans are completely homebound due to debilitating illness and other causes. another 3 to 15 percent lack the ability to leave the home without significant assistance and are functionally homebound.1 a large share of very high-cost patients are homebound, and many of them are elderly or poor. as provider organizations assume increasing risk in Medicare and Medicaid contracts, it is essential that they find ways to successfully manage homebound individuals.

presently there are few models to care for homebound patients in a proactive and integrated way.2 3 4 those that exist tend to serve small populations and are difficult to scale. Most are academic or Veterans affairs practices.5 the Centers for Medicare & Medicaid Services (CMS)-sponsored “Independence-at-home” demonstration projects have shown promise to broaden the range, but today the need for care of homebound patients far exceeds the supply.

SynerMed and MedZed partnered to create a program that addresses the needs of patients who infrequently visit the doctor’s office even though their care requirements are great. Some are truly homebound, and others are physically compromised. Many have an array of psychosocial challenges that make medical visits difficult and irregular. the goals of the program are to provide a consistent form of

primary care and to understand and address the unique medical and social challenges faced by these high-risk patients.

SynerMed, a medical services organization, operates independent practice associations that care for one million Medi-Cal, 40,000 Medicare, and 150,000 commercial beneficiaries across California. MedZed is a telemedicine-enabled home care company serving frail and high-risk patients through an innovative in-home patient Centered Medical home.

the two organizations developed a program to identify, recruit, and manage complex patients at home. the program utilizes specially trained nurses equipped with a mobile telemedicine platform, linked to remote primary care providers. In a typical visit, the nurse performs a variety of care management and nursing tasks in the patient’s home. then the nurse links via telemedicine to the remote pCp, who conducts a physical exam, incorporates the information from the first part of the visit, and develops an assessment and plan.

Just like a traditional in-person medical visit, the physician can diagnose, refer, prescribe, instruct the patient, and set follow-up intervals. a care coordinator assists with scheduling, transportation, and delivery

Jorge Weingarten, MD

Neil Solomon, MD

“Just like a traditional in-person medical visit, the physician can diagnose, refer, prescribe, instruct the patient, and set follow-up intervals.”


of equipment and medications, among other services. additional services are provided as needed for patients, including social work, behavioral health counseling, wound care, and coordination with specialists not directly associated with the program.

patients in the program have a wide array of medical and social issues. Many have typical chronic conditions, including diabetes, renal insufficiency, liver disease, and heart failure. Behavioral health issues and substance use disorder are also prevalent. Challenges of frailty, food insecurity, housing instability, social isolation, and other common effects of poverty are common in this population.

the program began in July 2016 in los angeles County. SynerMed identifies cases through multiple sources, including review of hospital census, case manager referral, and use of administrative data to screen for high-risk utilization patterns. Outreach is performed by MedZed staff bedside in the hospital, by telephone, and by knocking on patients’ doors. patients are invited into the program at no charge to them, and they are allowed to continue to see their existing primary care provider.

MedZed clinicians manage the medical conditions actively, coordinating with specialists and seeing patients frequently until they are stable. patients are instructed to call MedZed if they begin to feel sick to manage acute issues between scheduled follow-ups. MedZed care coordinators also perform telephonic outreach to confirm delivery of medications and equipment, ensure understanding of instructions, remind patients of upcoming appointments, and check in on current health status.

MedZed’s clinical team builds high levels of trust with patients and develops longitudinal relationships with them. they get to know patients’ families, too. the MedZed nurses often live in the communities where they see patients, so they are comfortable with and share similarities with their patient population. Most speak a second language. the primary care providers are skilled in the use of remote diagnostic equipment and with techniques to communicate effectively via teleconference. recently,

MedZed added capabilities in behavioral health and plans to expand into other specialties.

SynerMed’s utilization management staff assist with identification of new patients, selection of specialists, authorizations, ordering of durable medical equipment, and referrals to social services. the two organizations’ staffs work closely to coordinate care for patients, meeting weekly and speaking more frequently about individual patients. Data is shared between the partners through secure links. For example, SynerMed medical management staff are able to enter the patient’s medical record to place authorizations, view clinical information, and route notes to specialists.

the two organizations perform joint planning, looking to refine recruitment strategies, enhance care processes, and identify new opportunities to improve the model. early analyses indicate hospital admissions and er visits have dropped significantly in the population. as experience increases, we plan to conduct further analyses and share the findings. o

Neil A. Solomon, MD, is co-founder and Chief Medical Officer of MedZed. Jorge Weingarten, MD, is Chief Medical Officer at SynerMed.

References:1Ornstein, JAMA Intern Med. 2015;175(7):1180-1186.2De Jonge, J Am Geriatr Soc 62:1825–1831, 2014.3Melnick, HEALTH AFFAIRS 35, NO. 1 (2016): 28–354Christina Bielaszka-DuVernay, HEALTH AFFAIRS 30, NO. 3 (2011): 431–434

5Edwards, JAMA Intern Med. 2014;174(11):1796-1803.



Home-based Care: Operational Pearls from an integrated Care OrganizationBY lISa hUMphreYS, MD, aND JereMY rICh, DpM

primary care team-based coordination and proactive management are principal components of a cost-effective and sustainable healthcare system. a more specialized version of this model focuses on high-risk, mainly elderly and frail individuals—patients who may be more effectively treated in their homes.

In these models, a care coordination team works closely with the individual, caregivers, primary care providers, nurses, behavioral health specialists, and other professionals to improve care delivery, resulting in improved individual well-being and better outcomes. these home care models are gaining increased attention as the prevalence of multiple chronic conditions, complex care needs, and functional impairment within the aging population are vigorously escalating.

the healthCare partners Institute for applied research and education collaborates with DaVita healthCare partners (DhCp), a DaVita Medical Group, to examine, document, and share lessons learned to enhance primary care delivery systems. here, Jeremy rich, DpM, Director of the Institute, chats with lisa humphreys, MD, Corporate Medical Director, and Craig Depriester, Senior Director of Operations, both at DhCp, who oversee the house Calls home-based healthcare program in Southern California. they talk about their operational experiences while highlighting refinements and enhancements to care management—all towards the goal to better align patient needs and quality of care while reducing costs.

DHCp’s House Calls program is not a “hospital-at-home” program, nor targeted for moribund or bed-bound patients, per se. How do you determine which individuals are most appropriate for this level of care?

Our team determines whether a patient needs home care based on homebound status, caregiver situation, and severity of illness. For example, these patients often have been hospitalized, are debilitated, and need ongoing medical treatment. It makes sense to care for them in their homes, as it is very difficult to receive the necessary care in an office-based setting.

DHCp, in partnership with select Southern California universities, has examined primary care “teamlet” staffing within clinical care settings and high-risk programs. What do these home-based staffing structures look like?

In our organization, we employ an interdisciplinary approach to our high-risk patients, ensuring that a comprehensive set of evaluations is completed and that all patient needs, both medical and non-medical, are met. primarily, home visits are performed by nurse practitioners with close supervision by physicians skilled at taking care of patients with complex medical conditions. Social workers also do home visits to assess the home environment, coordinate supporting resources, and assist with psychosocial needs. and we have partnered with clinical pharmacists to support medication reconciliation efforts.

Jeremy Rich, DPM

Lisa Humphreys, MD

“The complexity of

House Calls patients

requires alignment

across the entire

medical team—

PCPs, specialists,

hospitalists,

social workers,

and disease

management

specialists.”


With such a complex program, how are metrics tracked, refined, and shared?

tracking metrics is a robustly dynamic part of our high-risk program. Our focus is access and speed, which are key to preventing readmissions. Specifically, that means follow-up on all of our high-risk patients within seven days of discharge and tight panel management. across clinicians, we publish metrics that indicate our performance in these key areas several times per month. this helps us identify gaps and areas for improvement. We are in the midst of rolling out tracking for patient experience, quality of care, and utilization of services within our patient population being served in these programs.

nationally, many providers report feeling overwhelmed by care processes, documentation, and compliance requirements. How does DHCp refine care delivery to make care management a “win-win” for patient and provider?

patients receiving home care services typically have a longer visit in the home than would occur in an office-based setting, allowing additional time for assessment and explanation of the treatment plan. this also provides the nurse practitioners time to build a relationship with patients that enables them to problem-solve other environmental issues that may exacerbate underlying medical conditions.

With the often complex care needs of home health patients and primary care team-based refinements, what changes in care delivery has your team initiated?

as we continue to refine our model, we have a number of learnings and key changes that are coming. One area of strength has been continuing to include the patient’s primary care physician (pCp) in the treatment plan, which

requires ongoing communication and coordination of services. Moving forward, we want to be more coordinated at the point of discharge—using laCe scores to funnel patients into the high-risk program and having ambulatory care managers follow patients throughout the high-risk program. the complexity of house Calls patients requires alignment across the entire medical team—pCps, specialists, hospitalists, social workers, and disease management specialists. While there has been great collaboration, we want to formalize the roles throughout the medical team and ensure consistency for each patient.

Can the development, implementation, and reach of home-centered care be diffused to organizations that may have less access to personnel and technical infrastructure?

New technology such as telehealth visits may help with geographic areas that do not have as many resources as needed for a home-based program. telehealth has been identified as an important opportunity in rural areas, for instance.



using Technology to Make Healthcare Delivery More Patient-CentricBY DaWN MarONeY, preSIDeNt OF MarKetS, alIGNMeNt healthCare

leveraging technology in healthcare is a no-brainer—it has the potential to increase access to care, reduce errors, and save on cost. But technology by itself is not the answer to delivering truly patient-centered care. technology is best applied when coupled with a high-touch, comprehensive care plan that not only centers on convenience, but also enhances the personal relationship patients have with their care teams.

this is the model we follow at alignment healthcare, where we put our members’ well-being at the heart of everything we do. We have seen tangible success by integrating a robust remote monitoring program with a concierge-level care model for the high-risk elderly patient population we serve.

We focus our efforts on providing members with the right amount of care when and where they need it—whether it’s through remote monitoring, in one of our care centers, at the hospital, or even in patients’ own homes. We know that when care is coordinated and personalized to best fit the patient’s health needs, we have better outcomes.

HOW We uSe ReMOTe MOniTORinG

through various tools and programs, we collect patient data and apply proprietary algorithms to anticipate members’ healthcare needs. We use these insights to enhance our relationship with our members, coordinate the delivery of their care, and share health information with their primary care physicians. Members get the benefit of a team approach and can access anyone on their care team whenever they need to, without having to worry about any gaps in knowledge. Our partnership with their physicians is strengthened by our vested interest in patients’ health.

take, for example, our partnership with allCare—an independent practice association (Ipa) represented by more than 1,000 private physicians in three California counties: Merced, San Joaquin, and Stanislaus. among other initiatives, alignment helped allCare establish its own remote monitoring program to give allCare clinicians a better understanding of their patient population.

Qualified patients receive a wireless 4G tablet, blood pressure cuff, pulse oximeter, and scale. all items are connected to the tablet via Bluetooth. We use the data collected to monitor each patient’s health status at any given time. Our clinical teams receive alerts when clinical interventions are required.

Modeled after alignment’s remote monitoring program and powered by the same data hub available in all our markets—California, North Carolina, and Florida—the allCare program serves patients who have recently been discharged from the hospital or those who have chronic conditions. For recently discharged patients, we help them navigate the transition back home—a time when they are often vulnerable to hospital readmission.

Outcomes have been positive: We’ve seen a reduction in hospital readmission rates among seniors enrolled in remote monitoring across all markets. While the 30-day national Medicare average readmission rate is 18 percent, seniors in alignment’s program saw hospital readmission rates of 7.2 percent across all markets in 2016—7.9 percent in North Carolina, 3.5 percent in California, and 0 percent in Florida.

“We have seen tangible success by integrating a robust remote monitoring program with a concierge-level care model for the high-risk elderly patient population.”


the program also helps patients manage their chronic conditions, including congestive heart failure, diabetes, hypertension, chronic obstructive pulmonary disease (COpD), and advanced kidney disease. alignment and primary care physicians receive daily health information—including vital sign checks and care plan updates—that comes straight from their patients’ homes. this way, we can coordinate hIpaa-compliant and fully encrypted virtual visits by phone or tablet when patients need the care, schedule a visit to one of our care centers, or visit patients at home.

OuR nexT COllAbORATiOn

this year, alignment and allCare launched a pilot home health program that sends clinicians to high-risk patients’ homes at least once a month. reserved for those who are homebound and require more intensive care, qualified patients in allCare’s service area receive in-home and telephonic care from alignment clinicians as a supplement to their medical treatments.

When patients need hospice, we focus our home visit program to provide compassionate care that prioritizes their autonomy, dignity, and comfort in the last stage of life. We use the same tools to help our patients feel comfortable and empowered, while also comforting family members, who receive a direct line to care coordinators.

at alignment, we use technology to make thoughtful and coordinated healthcare delivery more efficient. We conduct initial health assessments and annual follow-ups to place members in programs best suited for their individual needs. ensuring the successful application of technology in healthcare—especially as it relates to home

health—requires the implementation of innovative, patient-centric programs. pairing technology with comprehensive programs such as our chronic disease and home health programs allows us to more quickly realize what we all are striving toward: the delivery of compassionate and effective healthcare to those who need it most.

SHARinG ReSOuRCeS TO ACHieve beTTeR CARe COORDinATiOn

by MATT COuRy, CeO, AllCARe

through allCare’s relationship with alignment healthcare, the care we provide all our patients has improved. By investing in this payer-provider partnership, we are truly coordinating the care we deliver, especially for alignment health plan members.

together, we operate three clinics in two counties in Northern California. We established a hospitalist program based on alignment’s care model and a remote monitoring program that focuses on reducing hospital readmission rates. Our physicians are never in the dark regarding their patients’ health because they have access to real-time data. By working so closely with our patients’ health plan, there are no gaps in treatment or coverage, as we are all working toward the same goal.

the home visit program provides us another opportunity to ensure our patients are receiving the care they need in a more effective and convenient way. Our physicians train as a team with alignment clinicians to better manage our patients’ care. Implementing technology gives our patients more access to their physicians—and gives their physicians the ability to better coordinate care with their insurer. When we’re all on the same page, it’s the patients who benefit most. at the end of the day, that’s what matters most. o

Dawn Maroney is President of Markets for Alignment Healthcare, a company redefining the business of healthcare by shifting the focus from payments to people. Matt Coury is CEO of AllCare, a physician organization represented by over 1,000 private practice physicians in Merced, San Joaquin, and Stanislaus counties. Alignment Healthcare and AllCare work together to cut costs and improve lives by unraveling the inefficiencies of the current system to drive patients, providers, and payers toward a common goal of wellness.


Oregon’s Coordinated Care Organizations...continued from page 17

One challenge is the tracking and enrollment of uninsured, homeless individuals; this continues to perplex CCO staff. this is in the main a technical problem related to the loss of Oregon’s coverage exchange and transition to the federal exchange. a tough transition from a state-based enrollment system to the federal process resulted in a significant drop in enrollment of a few hundred thousand individuals in the second year of the Medicaid expansion coverage. as individual address locations changed, many thousands were lost from the system and could not be contacted for re-enrollment. there is frustration that the homeless sub-population could be attracted into the CCO model if a more effective enrollment system could be implemented.

CCOs have also struggled to find resources to provide and integrate transitional housing sources for the homeless—particularly homeless patients who are facing inpatient discharge. Many cited that housing

was “the number one social determinant” and admitted that there was little that could be done to address the lack of supply. Oregon homeowners have enjoyed rapidly increasing property values during this decade, but housing unaffordability is becoming an increasing problem. rents are among the highest of the West Coast cities. transitional housing supply and funding for development remain under-addressed problems.

Moving forward, Oregon has committed to a 3.4 percent statewide cap on the growth of healthcare expenditures. It will continue to rely on its 16 CCOs to deliver value and impose restraint. Oregon’s CCO model teaches us that the formal, visible inclusion of patients to the CCO is superior to the current Medicare Shared Savings program aCO model.

Because of the strong development of the medical home model for primary care, Medicaid beneficiaries know that they have a preventive care base that will keep them out of emergency departments, creating a “culture of coverage” that promotes buy-in toward a healthier lifestyle. Well done, Oregon. o

The DHCp home care program has been in existence for about nine years. Has any specific critical input from your teammates helped refine the program in a forward-thinking way?

We are constantly evaluating our criteria to enter our home-based programs, such as using the laCe score to refer patients. equally important, we are evaluating the most efficient way to coordinate patient care and the right time to transition patients back to office-based care. after our patients have stabilized post-discharge, we want to be thoughtful about providing efficient home-based care and then transitioning patients back to their regular pCp with the proper handoff and medical notes. We also often ask if we may be missing any patient populations who would benefit from this type of care. to that end, we are developing closer relationships with the outpatient team to drive referrals before the patient goes to the hospital. While it’s critical to properly manage a patient after leaving the hospital, we want to start working with our chronically ill patients before they have to visit the er.

What is your most salient “pearl” or takeaway for those thinking of creating a home-based program?

I recommend having a well-defined patient population who would be eligible to receive these types of services. this will allow you to scope the size of your program and estimate the impact on the overall patient population. o

Jeremy Rich, DPM, is Director of the HealthCare Partners Institute for Applied Research and Education. For more information, contact him at [email protected]. Lisa Humphreys, MD, is Corporate Medical Director of DaVita Healthcare Partners. The authors gratefully acknowledge Craig DePriester, Senior Director of Operations, DHCP, for his critical input.

bibliographySM Shortell, BY Poon, PP Ramsay, et al, “Multilevel Analysis of Patient Engagement and Patient-Reported Outcomes in Primary Care Practices of Accountable Care Organizations,” Journal of General Internal Medicine, 2017 Jun;32(6):640-47.

GA Melnick, L Green, J Rich, “House Calls: California Program For Homebound Patients Reduces Monthly Spending, Delivers Meaningful Care,” Health Affairs, 2016 Jan;35(1):28-35.

SM Grace, J Rich, W Chin, HP Rodriguez, “Implementing Interdisciplinary Teams Does Not Necessarily Improve Primary Care Practice Climate,” American Journal of Medical Quality, 2016 Jan-Feb;31(1):5-11.

SM Grace, J Rich, W Chin, HP Rodriguez, “Fidelity of implementation to a care team redesign and improved outcomes of diabetes care,” International Journal for Quality in Health Care, 2015 Feb;27(1):60-6.

SM Grace, J Rich, W Chin, HP Rodriguez, “Flexible implementation and integration of new team members to support patient-centered care,” Healthcare. 2014 Jul;2(2):145-51.

Operational Pearls....continued from page 43

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Formula for Success in New Payment Models The new Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), which moves the physician payment model away from fee-for-service to value-based patient care, has some healthcare professionals understandably concerned about adding another twist to healthcare reimbursements. At Brown & Toland Physicians, providing value-based care to patients is a familiar practice. Many of our physicians are already meeting MACRA requirements through the use of e-tools, improved quality clinical practices and effective management of costs.

With Brown & Toland’s experience across numerous value-based accountable care projects for HMO and PPO patients, we have fine-tuned the formula for delivering high-quality, cost-effective care while succeeding in risk-adjustment payments models. One such example includes our participation in the CMS Pioneer Accountable Care program, which generated more than $15 million in savings for the care of 17,000 patients.

It is accountable care experiences like this that will help physician-led groups and their partners find the winning formulas for success in the new payment models to come.

To learn more about Brown & Toland Physicians and how we have achieved success through value-based payment models, please visit our website at brownandtoland.com.

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