46 characteristics associated with medication adherence … · 2019-11-22 · 46 characteristics...

Characteristics Associated With Medication Adherence Among New Omalizumab Users46

James Zazzali, PhD, MPH1; Michael S. Broder, MD, MSHS2; Eunice Chang, PhD2 1Genentech Inc., South San Francisco, CA; 2Partnership for Health Analytic Research, Beverly Hills, CA

ABSTRACTOBJECTIVE: Adherence to omalizumab (OMA) therapy has not been well studied. We sought to identify characteristics associated with adherence among new OMA users. METHODS: This was a retrospective cohort analysis using a HIPAA-compliant claims database. The study identified asthma patients who were ≥12 years old, newly treated with OMA between 7/1/2004 and 6/30/2007, and enrolled for 1 year before and 1 year after the first OMA claim. Adherence was measured by medication possession ratio (MPR) (total days of medication supplied ÷ 365) with each OMA claim considered a 28-day supply. Therapy step, as defined by the EPR3 guidelines, was assigned using a published algorithm. A base linear regression model was conducted with MPR as the dependent variable and demographics, physician specialty, respiratory comorbidities, asthma control, therapy step, and medication ratio forced into the model as independent variables. Other comorbidities were considered with forward selection and retained if significant at p<.05.RESULTS: We identified 766 new OMA users; mean age was 43 (SD 14) years, and 61% (n=466) were female. Forty-two percent of patients had allergists as their usual source of care, 20% pulmonologists, 28.3% primary care physicians, and the remainder other/unspecified. The mean number of chronic conditions was 5 (SD 2). Before starting OMA, most of patients were on EPR3 Step 5 therapy (28%), followed by Step 4 (18%), Step 3 (16%), Step 2 (15%), Step 1 (6%), and Step 6 (5%). Mean MPR in the year after treatment initiation was 0.68 (SD 0.30), and 55% persisted with therapy for at least 1 year. The final model included the base variables and diseases of circulatory system (the only additional significant predictor). Significant predictors of higher MPR were: care provided by allergists or pulmonologists, chronic otitis media, 5 or 6 vs ≥7 chronic conditions, and no disease of the circulatory system.CONCLUSIONS: We found MPR for omalizumab to be higher on average than what has been reported for combination corticosteroid/long-acting beta-agonist therapy. Care by an allergist or pulmonologist was associated with greater adherence. Confounding by disease severity is possible, but the relationship was significant after controlling for therapy step. If this finding is confirmed in other studies, it supports the value of specialist care for patients with difficult to treat asthma.

CONCLUSIONS• Among new omalizumab users, we estimated the MPR to be 0.68 with 54.7%

persisting on omalizumab at one year after initiating therapy.

• Omalizumab adherence and persistence are consistent with previously published reports, although this analysis indicates slightly higher estimates.

• The number of chronic conditions and select respiratory comorbidities were significant predictors of adherence and persistence in our multivariate models.

LIMITATIONS• Administrative claims data do not indicate the dosing schedule for omalizumab;

in this analysis, each dose of omalizumab was assumed to be a 28 day supply.

• Inclusion of concomitant asthma medications as covariates is indicative only of those medications filled and not reflective of patient adherence to therapy.

BACKGROUND• Lack of adherence to prescribed treatments for asthma is a well-known problem.

Rates of nonadherence range from 30% to 70%.1-3

• Poor asthma medication adherence is associated with decreases in asthma control and increases in emergency department visits, hospitalizations, and the need for oral corticosteroids.3,4

• Omalizumab, a humanized monoclonal antibody targeting immunoglobulin E, is approved in the United States for the treatment of adults and adolescents (≥12 years) with moderate to severe persistent allergic asthma that is inadequately controlled with inhaled corticosteroids.5

• Adherence to omalizumab therapy has not been well studied. One prior analysis of asthma patients newly treated with omalizumab estimated adherence rates to be 64.6% with 54% persisting up to one year.6

OBJECTIVE• To identify characteristics associated with adherence and persistence among new

omalizumab users

METHODSStudy Design• A retrospective cohort analysis using a HIPAA-compliant administrative claims

database of 10 million covered lives representing all major regions of the United States.

• Eligible patients were ≥12 years old, diagnosed with asthma, newly treated with omalizumab between 7/1/2004 and 6/30/2007, and followed for a year (Figures 1 and 2).

RESULTS• We identified 766 new omalizumab users; average age was 43.4 years and 61%

were female. Fifty percent of patients received asthma care from an allergist, 28% a pulmonologist, and 17% a primary care physician.

• Overall, the MPR was 0.68 (SD, ± 0.30). MPR stratified by baseline measures are presented in Table 1 and results of the multivariate analysis in Table 2.

• During follow-up, 45.3% of patients discontinued treatment. Mean (SD) time to discontinuation/end of study was 256.5 (131.6) days; median was 353 days (Table 3, Figure 3).

• The risk of discontinuing omalizumab was examined across a number of variables (Table 4).

REFERENCES1. Bender B et al. Ann Allergy Asthma Immunol. 2000;

85(5):416-421.2. Bender BG et al. Ann Allergy Asthma Immunol. 2007;

98(4):322-328.3. World Health Organization. Adherence to long-term

therapies: evidence for action. Geneva, Switzerland: World Health Organization; 2003.

4. Williams LK et al. J Allergy Clin Immunol. 2004;114(6):1288-1293.

5. Xolair [prescribing information]. South San Francisco, CA: Genentech USA, Inc.; 2010.

6. Broder MS et al. Allergy Asthma Proc. 2009;30(2):148-157.7. Deyo RA et al. J Clin Epidemiol. 1992;45(6):613-619.8. National Asthma Education and Prevention Program. Expert

Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007;120(5 suppl):S94-S138.

Index Date

First claim for omalizumab in ID period

1-year period (Preindex period)

7/1/03 6/30/08

6/30/077/1/04

Identification (ID) Period

1-year period (Postindex period)

Figure 1. Study Timeline

% o

f P

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on

Tre

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ent

Days to Discontinue Omalizumab

100

75

50

25

0

0 50 100 150 200 250 300 350 400

Figure 3. Days to Discontinuation of Omalizumab.

Study Outcomes• Adherence to omalizumab therapy during the postindex period, as measured by the

medication possession ratio (MPR) – Calculated as the total days of medication supplied over the year, divided by 365 – Each omalizumab claim was considered a 28-day supply • Medication persistence during the postindex period, as measured by time

to discontinuation – Calculated as the number of days on omalizumab with no gaps of more than

45 daysStatistical Analysis• To evaluate the association of baseline measures (patient demographic and clinical

characteristics) with omalizumab adherence and persistence, we conducted a linear regression model with adherence (MPR) as the continuous dependent variable and all baseline measures as independent variables and a similar logistic regression model to predict persistence at one year.

– Based on bivariate analysis results and clinical relevance, demographics (age, sex, and region), asthma physician specialty, number of chronic conditions, evidence of allergy, respiratory-specific comorbidities, therapy step, and medication ratio were first included in the linear regression model; we then used forward selection to identify significant results for other baseline measures.

3456 patients with a claim of omalizumab in ID period

(7/1/2004–6/30/2007)

n=3391

n=3377

n=2886

n=766

65 patients with age <12 years on the index date (the date of �rst omalizumab claim in ID period)

14 patients had no asthma diagnosis in the preindex or postindex period

491 previously used omalizumab

2120 patients were not continuously enrolled in the preindex and postindex periods

Figure 2. Cohort Selection for Omalizumab New Users.

ID = identification.

N (%)MPR

Mean (SD) P Value

All 766 (100.0) 0.68 (0.30)

Demographics

Age, y (mean 43.4; SD 14.5) 0.157

12-17 68 (8.9) 0.72 (0.28)

18-34 111 (14.5) 0.62 (0.34)

35-44 183 (23.9) 0.66 (0.30)

45-54 234 (30.5) 0.68 (0.30)

55-64 141 (18.4) 0.71 (0.27)

65+ 29 (3.8) 0.65 (0.24)

Sex 0.174

Female 466 (60.8) 0.69 (0.30)

Male 300 (39.2) 0.66 (0.30)

Region 0.056

Midwest 184 (24.0) 0.71 (0.28)

Northeast 86 (11.2) 0.62 (0.32)

South 387 (50.5) 0.66 (0.30)

West 109 (14.2) 0.70 (0.27)

Physician Specialty

Usual asthma care physiciana 0.020

Pulmonologist 214 (27.9) 0.68 (0.28)

Primary care 128 (16.7) 0.64 (0.31)

Allergists 381 (49.7) 0.69 (0.29)

Other 22 (2.9) 0.66 (0.36)

Unknown 21 (2.7) 0.48 (0.39)

General Comorbidities

No. of chronic conditions (mean 4.7; SD 2.3) 0.047

1-2 155 (20.2) 0.63 (0.33)

3-4 227 (29.6) 0.69 (0.29)

5-6 216 (28.2) 0.71 (0.27)

7+ 168 (21.9) 0.65 (0.29)

Charlson Comorbidity Index7 (mean 1.8; SD 1.7) 0.967

1 530 (69.2) 0.68 (0.30)

2 86 (11.2) 0.68 (0.29)

3+ 150 (19.6) 0.67 (0.29)

Evidence of allergy <.001

No 57 (7.4) 0.55 (0.34)

Yes 709 (92.6) 0.69 (0.29)

Respiratory-Specific Comorbidities

COPD 0.338

No 577 (75.3) 0.67 (0.31)

Yes 189 (24.7) 0.69 (0.27)

Sinusitis 0.551

No 243 (31.7) 0.67 (0.31)

Yes 523 (68.3) 0.68 (0.29)

Rhinitis <0.001

No 93 (12.1) 0.57 (0.33)

Yes 673 (87.9) 0.69 (0.29)

Tonsillitis 0.321

No 731 (95.4) 0.67 (0.30)

Yes 35 (4.6) 0.72 (0.28)

Acute upper respiratory infection 0.471

No 515 (67.2) 0.67 (0.30)

Yes 251 (32.8) 0.69 (0.28)

Conjunctivitis 0.894

No 619 (80.8) 0.68 (0.30)

Yes 147 (19.2) 0.67 (0.29)

Chronic otitis media 0.002

No 746 (97.4) 0.67 (0.30)

Yes 20 (2.6) 0.81 (0.17)

Nasal polyposis 0.073

No 663 (86.6) 0.68 (0.29)

Yes 103 (13.4) 0.63 (0.32)

Cough 0.427

No 381 (49.7) 0.67 (0.31)

Yes 385 (50.3) 0.68 (0.28)

N (%)MPR

Mean (SD) P Value

All 766 (100.0) 0.68 (0.30)

Asthma Control in the Preindex Period

Poor asthma controlb 0.096

No 191 (24.9) 0.64 (0.32)

Yes 575 (75.1) 0.69 (0.29)

Asthma-related inpatient hospitalization 0.340

No 657 (85.8) 0.68 (0.30)

Yes 109 (14.2) 0.65 (0.30)

Asthma-related ED visit 0.412

No 705 (92.0) 0.67 (0.30)

Yes 61 (8.0) 0.71 (0.29)

Two or more oral corticosteroid prescriptions filled 0.031

No 265 (34.6) 0.64 (0.32)

Yes 501 (65.4) 0.69 (0.28)

Six or more short-acting beta-agonist prescriptions filled 0.310

No 434 (56.7) 0.67 (0.30)

Yes 332 (43.3) 0.69 (0.29)

EPR-3 Guidelines8 Therapy Step in Preindex Period

Therapy step prior to initiating omalizumab 0.006

No asthma meds 68 (8.9) 0.56 (0.33)

Step 1 44 (5.7) 0.61 (0.32)

Step 2 112 (14.6) 0.67 (0.30)

Step 3 121 (15.8) 0.73 (0.27)

Step 4 136 (17.8) 0.69 (0.28)

Step 5 214 (27.9) 0.69 (0.29)

Step 6 37 (4.8) 0.63 (0.33)

Unclassified 34 (4.4) 0.72 (0.28)

Medication Ratioc and Other Asthma Medication Use in the Preindex Period

Medication ratio (mean 0.64; SD 0.28 among 718 patients with medication ratios) 0.003

Low ratio (<0.5) 197 (25.7) 0.64 (0.31)

High ratio (≥0.5) 521 (68.0) 0.70 (0.28)

Missing (no controller or reliever)

48 (6.3) 0.55 (0.35)

Short-acting beta-agonist inhalers 0.044

No 115 (15.0) 0.62 (0.32)

Yes 651 (85.0) 0.68 (0.29)

Anticholinergics 0.077

No 521 (68.0) 0.66 (0.30)

Yes 245 (32.0) 0.70 (0.29)

Oral corticosteroids 0.119

No 153 (20.0) 0.64 (0.32)

Yes 613 (80.0) 0.68 (0.29)

ICS/LABA combination 0.051

No 240 (31.3) 0.64 (0.31)

Yes 526 (68.7) 0.69 (0.29)

ICS alone 0.286

No 450 (58.7) 0.67 (0.31)

Yes 316 (41.3) 0.69 (0.28)

LABA alone 0.790

No 643 (83.9) 0.67 (0.30)

Yes 123 (16.1) 0.68 (0.30)

Mast cell stabilizers 0.108

No 734 (95.8) 0.67 (0.30)

Yes 32 (4.2) 0.76 (0.25)

Methylxanthines 0.810

No 670 (87.5) 0.67 (0.30)

Yes 96 (12.5) 0.68 (0.26)

Leukotriene receptor antagonists 0.078

No 221 (28.9) 0.65 (0.31)

Yes 545 (71.1) 0.69 (0.29)

Table 1. MPR of Omalizumab Stratified by Patient Demographics and Clinical Characteristics

aThe usual asthma care physician was determined by the largest plurality of office visits with evaluation and management services and asthma diagnosis. bAsthma-related inpatient hospitalization, asthma-related ED visit, ≥2 oral corticosteroid prescriptions filled, or ≥6 short-acting beta-agonist prescriptions filled.cMedication ratio is units of asthma controllers to units of controllers + units of relievers.COPD = chronic obstructive pulmonary disease; ED = emergency department; EPR-3 = National Asthma Education and Prevention Program Expert Panel Report 3; ICS = inhaled corticosteroid; LABA = long-acting beta-agonist; MPR = medication possession ratio.

Omalizumab New Users(N=766)

MPR (Range 0-1) Mean (SD) 0.68 (0.30)[Median] [0.80]

Discontinued omalizumab n (%) 347 (45.3)Days to discontinuation/end of study Mean (SD) 256.5 (131.6)

[Median] [353]Number of omalizumab claims Mean (SD) 10.1 (5.4)

[Median] [11]1 n (%) 64 (8.4)2-5 n (%) 94 (12.3)6-11 n (%) 249 (32.5)12+ n (%) 359 (46.9)

Table 3. Omalizumab Use in the Postindex Period

HR (95% CI) P ValueAge, y 12-17 vs 65+ 0.82 (0.41 - 1.67) 0.576 18-34 vs 65+ 1.15 (0.64 - 2.16) 0.655 35-44 vs 65+ 0.86 (0.50 - 1.57) 0.600 45-54 vs 65+ 0.81 (0.48 - 1.46) 0.457 55-64 vs 65+ 0.76 (0.44 - 1.38) 0.344Female vs male 0.83 (0.66 - 1.05) 0.121Region Midwest vs West 0.76 (0.52 - 1.12) 0.164 Northeast vs West 0.98 (0.63 - 1.51) 0.917 South vs West 1.16 (0.84 - 1.62) 0.380Usual asthma care physician specialty Allergist vs primary/other 0.85 (0.64 - 1.13) 0.264 Pulmonologist vs primary/other 0.84 (0.62 - 1.14) 0.273No. of chronic conditions 1-2 vs 7+ 0.89 (0.59 - 1.35) 0.596 3-4 vs 7+ 0.81 (0.58 - 1.13) 0.212 5-6 vs 7+ 0.69 (0.51 - 0.94) 0.020Evidence of allergy 0.97 (0.53 - 1.71) 0.914Therapy step No asthma medication vs Step 6 1.25 (0.64 - 2.49) 0.518 Step 1 vs Step 6 1.21 (0.61 - 2.44) 0.580 Step 2 vs Step 6 1.18 (0.69 - 2.13) 0.560 Step 3 vs Step 6 0.79 (0.46 - 1.44) 0.430 Step 4 vs Step 6 0.92 (0.54 - 1.66) 0.769 Step 5 vs Step 6 0.90 (0.54 - 1.58) 0.689 Unclassified vs Step 6 0.73 (0.33 - 1.59) 0.437Medication ratio Low ratio (<0.5) vs high ratio (≥0.5) 1.18 (0.66 - 2.07) 0.563 Missing (no controller or reliever) vs high ratio (≥0.5) 1.36 (0.77 - 2.43) 0.289COPD 0.93 (0.71 - 1.22) 0.613Sinusitis 0.99 (0.77 - 1.27) 0.916Rhinitis 0.65 (0.40 - 1.09) 0.082Tonsillitis 0.58 (0.29 - 1.02) 0.083Acute upper respiratory infection 1.12 (0.88 - 1.42) 0.341Conjunctivitis 1.13 (0.85 - 1.49) 0.384Chronic otitis media 0.61 (0.26 - 1.24) 0.218Nasal polyposis 1.46 (1.05 - 2.00) 0.019Cough 0.95 (0.75 - 1.19) 0.627Diseases of the circulatory system 1.32 (1.00 - 1.76) 0.052

Table 4. Risk of Discontinuing Omalizumab: Adjusted Hazard Ratios and 95% Confidence Intervals

CI = confidence interval; HR = hazard ratio.

Coefficient SE P ValueIntercept 0.49 0.10 <0.001Age, y 12-17 vs 65+ 0.04 0.07 0.567 18-34 vs 65+ -0.04 0.06 0.520 35-44 vs 65+ 0.01 0.06 0.845 45-54 vs 65+ 0.04 0.06 0.483 55-64 vs 65+ 0.06 0.06 0.298Female vs male 0.03 0.02 0.268Region Midwest vs West 0.03 0.04 0.375 Northeast vs West -0.03 0.04 0.545 South vs West -0.03 0.03 0.290Usual asthma care physician specialty Allergist vs primary/other 0.04 0.03 0.178 Pulmonologist vs primary/other 0.04 0.03 0.193No. of chronic conditions 1-2 vs 7+ -0.03 0.04 0.522 3-4 vs 7+ 0.03 0.03 0.334 5-6 vs 7+ 0.07 0.03 0.028Evidence of allergy 0.06 0.06 0.351Therapy step No asthma medication vs Step 6 -0.02 0.07 0.818 Step 1 vs Step 6 -0.01 0.07 0.933 Step 2 vs Step 6 0.01 0.06 0.817 Step 3 vs Step 6 0.08 0.06 0.138 Step 4 vs Step 6 0.04 0.05 0.506 Step 5 vs Step 6 0.04 0.05 0.443 Unclassified vs Step 6 0.10 0.07 0.182Medication ratio Low ratio (<0.5) vs high ratio (≥0.5) -0.03 0.06 0.602 Missing (no controller or reliever) vs high ratio (≥0.5)

-0.08 0.06 0.211

COPD 0.03 0.03 0.317Sinusitis 0.00 0.02 0.927Rhinitis 0.08 0.05 0.112Tonsillitis 0.07 0.05 0.178Acute upper respiratory infection 0.00 0.02 0.950Conjunctivitis -0.02 0.03 0.477Chronic otitis media 0.13 0.07 0.050Nasal polyposis -0.09 0.03 0.005Cough 0.01 0.02 0.684Diseases of the circulatory system -0.07 0.03 0.008

Table 2. Multivariate Analysis: Characteristics Associated With Omalizumab MPR

COPD = chronic obstructive pulmonary disease; MPR = medication possession ratio.

This study was supported by Genentech, Inc., South San Francisco, CA, and Novartis Pharmaceuticals Corporation, East Hanover, NJ, and third-party writing assistance for this poster was provided by Genentech, Inc., South San Francisco CA, and Novartis Pharmaceuticals, East Hanover, NJ.

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erap

y st

ep. I

f thi

s fin

din

g is

con

firm

ed in

oth

er

stud

ies,

it s

upp

orts

the

val

ue o

f sp

ecia

list

care

for

pat

ient

s w

ith d

ifficu

lt to

tr

eat

asth

ma.

CO

NC

LUS

ION

S•

Am

ong

new

om

aliz

umab

use

rs, w

e es

timat

ed t

he M

PR

to

be

0.68

with

54.

7%

per

sist

ing

on o

mal

izum

ab a

t on

e ye

ar a

fter

initi

atin

g th

erap

y.

• O

mal

izum

ab a

dhe

renc

e an

d p

ersi

sten

ce a

re c

onsi

sten

t w

ith p

revi

ousl

y p

ublis

hed

re

por

ts, a

lthou

gh t

his

anal

ysis

ind

icat

es s

light

ly h

ighe

r es

timat

es.

• T

he n

umb

er o

f chr

onic

con

diti

ons

and

sel

ect

resp

irato

ry c

omor

bid

ities

wer

e si

gnifi

cant

pre

dic

tors

of a

dhe

renc

e an

d p

ersi

sten

ce in

our

mul

tivar

iate

mod

els.

LIM

ITA

TIO

NS

• A

dm

inis

trat

ive

clai

ms

dat

a d

o no

t in

dic

ate

the

dos

ing

sche

dul

e fo

r om

aliz

umab

; in

thi

s an

alys

is, e

ach

dos

e of

om

aliz

umab

was

ass

umed

to

be

a 28

day

sup

ply

.

• In

clus

ion

of c

onco

mita

nt a

sthm

a m

edic

atio

ns a

s co

varia

tes

is in

dic

ativ

e on

ly o

f th

ose

med

icat

ions

fille

d a

nd n

ot r

eflec

tive

of p

atie

nt a

dhe

renc

e to

the

rap

y.

BA

CK

GR

OU

ND

• L

ack

of a

dhe

renc

e to

pre

scrib

ed t

reat

men

ts fo

r as

thm

a is

a w

ell-

know

n p

rob

lem

. R

ates

of n

onad

here

nce

rang

e fr

om 3

0% t

o 70

%.1-

3

• P

oor

asth

ma

med

icat

ion

adhe

renc

e is

ass

ocia

ted

with

dec

reas

es in

ast

hma

cont

rol

and

incr

ease

s in

em

erge

ncy

dep

artm

ent

visi

ts, h

osp

italiz

atio

ns, a

nd t

he n

eed

for

or

al c

ortic

oste

roid

s.3,

4

• O

mal

izum

ab, a

hum

aniz

ed m

onoc

lona

l ant

ibod

y ta

rget

ing

imm

unog

lob

ulin

E,

is a

pp

rove

d in

the

Uni

ted

Sta

tes

for

the

trea

tmen

t of

ad

ults

and

ad

oles

cent

s

(≥12

yea

rs) w

ith m

oder

ate

to s

ever

e p

ersi

sten

t al

lerg

ic a

sthm

a th

at is

inad

equa

tely

co

ntro

lled

with

inha

led

cor

ticos

tero

ids.

5

• A

dhe

renc

e to

om

aliz

umab

the

rap

y ha

s no

t b

een

wel

l stu

die

d. O

ne p

rior

anal

ysis

of

asth

ma

pat

ient

s ne

wly

tre

ated

with

om

aliz

umab

est

imat

ed a

dhe

renc

e ra

tes

to b

e 64

.6%

with

54%

per

sist

ing

up t

o on

e ye

ar.6

OB

JEC

TIV

E•

To

iden

tify

char

acte

ristic

s as

soci

ated

with

ad

here

nce

and

per

sist

ence

am

ong

new

om

aliz

umab

use

rs

ME

TH

OD

SS

tud

y D

esig

n•

A r

etro

spec

tive

coho

rt a

naly

sis

usin

g a

HIP

AA

-com

plia

nt a

dm

inis

trat

ive

clai

ms

dat

abas

e of

10

mill

ion

cove

red

live

s re

pre

sent

ing

all m

ajor

reg

ions

of t

he

Uni

ted

Sta

tes.

• E

ligib

le p

atie

nts

wer

e ≥1

2 ye

ars

old

, dia

gnos

ed w

ith a

sthm

a, n

ewly

tre

ated

w

ith o

mal

izum

ab b

etw

een

7/1/

2004

and

6/3

0/20

07, a

nd fo

llow

ed fo

r a

year

(F

igur

es 1

and

2).

RE

SU

LTS

• W

e id

entifi

ed 7

66 n

ew o

mal

izum

ab u

sers

; ave

rage

age

was

43.

4 ye

ars

and

61%

w

ere

fem

ale.

Fift

y p

erce

nt o

f pat

ient

s re

ceiv

ed a

sthm

a ca

re fr

om a

n al

lerg

ist,

28%

a

pul

mon

olog

ist,

and

17%

a p

rimar

y ca

re p

hysi

cian

. •

Ove

rall,

the

MP

R w

as 0

.68

(SD

, ± 0

.30)

. MP

R s

trat

ified

by

bas

elin

e m

easu

res

are

pre

sent

ed in

Tab

le 1

and

res

ults

of t

he m

ultiv

aria

te a

naly

sis

in T

able

2.

• D

urin

g fo

llow

-up

, 45.

3% o

f pat

ient

s d

isco

ntin

ued

tre

atm

ent.

Mea

n (S

D) t

ime

to d

isco

ntin

uatio

n/en

d o

f stu

dy

was

256

.5 (1

31.6

) day

s; m

edia

n w

as 3

53 d

ays

(T

able

3, F

igur

e 3)

.•

The

ris

k of

dis

cont

inui

ng o

mal

izum

ab w

as e

xam

ined

acr

oss

a nu

mb

er o

f var

iab

les

(Tab

le 4

).

RE

FER

EN

CE

S1.

Ben

der

B e

t al

. Ann

Alle

rgy

Ast

hma

Imm

unol

. 200

0;85

(5):4

16-4

21.

2. B

end

er B

G e

t al

. Ann

Alle

rgy

Ast

hma

Imm

unol

. 200

7;98

(4):3

22-3

28.

3. W

orld

Hea

lth O

rgan

izat

ion.

Ad

here

nce

to lo

ng-t

erm

th

erap

ies:

evi

den

ce fo

r ac

tion.

Gen

eva,

Sw

itzer

land

: W

orld

Hea

lth O

rgan

izat

ion;

200

3.4.

Will

iam

s LK

et

al. J

Alle

rgy

Clin

Imm

unol

. 200

4;11

4(6)

:12

88-1

293.

5. X

olai

r [p

resc

ribin

g in

form

atio

n]. S

outh

San

Fra

ncis

co, C

A:

Gen

ente

ch U

SA

, Inc

.; 20

10.

6. B

rod

er M

S e

t al

. Alle

rgy

Ast

hma

Pro

c. 2

009;

30(2

):148

-157

.7.

Dey

o R

A e

t al

. J C

lin E

pid

emio

l. 19

92;4

5(6)

:613

-619

.8.

Nat

iona

l Ast

hma

Ed

ucat

ion

and

Pre

vent

ion

Pro

gram

. Exp

ert

Pan

el R

epor

t 3

(EP

R-3

): G

uid

elin

es fo

r th

e D

iagn

osis

and

M

anag

emen

t of

Ast

hma-

Sum

mar

y R

epor

t 20

07. J

Alle

rgy

Clin

Imm

unol

. 200

7;12

0(5

sup

pl):

S94

-S13

8.

In

dex

Dat

eFi

rst

clai

m f

or

om

aliz

umab

in ID

per

iod

1-ye

ar p

erio

d (P

rein

dex

per

iod

)

7/1/

036/

30/0

8

6/30

/07

7/1/

04

Iden

tifi

cati

on

(ID) P

erio

d

1-ye

ar p

erio

d (P

ost

ind

ex p

erio

d)

Fig

ure

1. S

tud

y Ti

mel

ine

% of Patients on Treatment

Day

s to

Dis

cont

inue

Om

aliz

umab

100 75 50 25 0

050

100

150

200

250

300

350

400

Fig

ure

3. D

ays

to D

isco

ntin

uatio

n of

Om

aliz

umab

.

Stu

dy

Out

com

es•

Ad

here

nce

to o

mal

izum

ab t

hera

py

dur

ing

the

pos

tind

ex p

erio

d, a

s m

easu

red

by

the

med

icat

ion

pos

sess

ion

ratio

(MP

R)

– C

alcu

late

d a

s th

e to

tal d

ays

of m

edic

atio

n su

pp

lied

ove

r th

e ye

ar, d

ivid

ed b

y 36

5

–

Eac

h om

aliz

umab

cla

im w

as c

onsi

der

ed a

28-

day

sup

ply

•

Med

icat

ion

per

sist

ence

dur

ing

the

pos

tind

ex p

erio

d, a

s m

easu

red

by

time

to d

isco

ntin

uatio

n

–

Cal

cula

ted

as

the

num

ber

of d

ays

on o

mal

izum

ab w

ith n

o ga

ps

of m

ore

than

45

day

sS

tati

stic

al A

naly

sis

• T

o ev

alua

te t

he a

ssoc

iatio

n of

bas

elin

e m

easu

res

(pat

ient

dem

ogra

phi

c an

d c

linic

al

char

acte

ristic

s) w

ith o

mal

izum

ab a

dhe

renc

e an

d p

ersi

sten

ce, w

e co

nduc

ted

a li

near

re

gres

sion

mod

el w

ith a

dhe

renc

e (M

PR

) as

the

cont

inuo

us d

epen

den

t va

riab

le a

nd

all b

asel

ine

mea

sure

s as

ind

epen

den

t va

riab

les

and

a s

imila

r lo

gist

ic r

egre

ssio

n m

odel

to

pre

dic

t p

ersi

sten

ce a

t on

e ye

ar.

– B

ased

on

biv

aria

te a

naly

sis

resu

lts a

nd c

linic

al r

elev

ance

, dem

ogra

phi

cs (a

ge,

sex,

and

reg

ion)

, ast

hma

phy

sici

an s

pec

ialty

, num

ber

of c

hron

ic c

ond

ition

s,

evid

ence

of a

llerg

y, r

esp

irato

ry-s

pec

ific

com

orb

iditi

es, t

hera

py

step

, and

m

edic

atio

n ra

tio w

ere

first

incl

uded

in t

he li

near

reg

ress

ion

mod

el; w

e th

en u

sed

fo

rwar

d s

elec

tion

to id

entif

y si

gnifi

cant

res

ults

for

othe

r b

asel

ine

mea

sure

s.

3456

pat

ient

s w

ith a

cla

im

of o

mal

izum

ab in

ID p

erio

d(7

/1/2

004–

6/30

/200

7)

n=33

91

n=33

77

n=28

86

n=76

6

65 p

atie

nts

with

age

<12

yea

rs o

n th

e in

dex

dat

e (th

e d

ate

of �

rst

omal

izum

ab c

laim

in ID

per

iod

)

14 p

atie

nts

had

no

asth

ma

dia

gnos

is

in t

he p

rein

dex

or

pos

tind

ex p

erio

d

491

pre

viou

sly

used

om

aliz

umab

2120

pat

ient

s w

ere

not

cont

inuo

usly

enr

olle

d

in t

he p

rein

dex

and

pos

tind

ex p

erio

ds

Fig

ure

2. C

ohor

t S

elec

tion

for

Om

aliz

umab

New

Use

rs.

ID =

iden

tifica

tion.

N(%

)M

PR

M

ean

(SD

)P

Val

ue

All

766

(100

.0)

0.68

(0.3

0)

Dem

og

rap

hics

Ag

e, y

(mea

n 43

.4; S

D 1

4.5)

0.15

7

12-

1768

(8.9

)0.

72 (0

.28)

18-

3411

1(1

4.5)

0.62

(0.3

4)

35-

4418

3(2

3.9)

0.66

(0.3

0)

45-

5423

4(3

0.5)

0.68

(0.3

0)

55-

6414

1(1

8.4)

0.71

(0.2

7)

65+

29(3

.8)

0.65

(0.2

4)

Sex

0.17

4

Fem

ale

466

(60.

8)0.

69 (0

.30)

Mal

e30

0(3

9.2)

0.66

(0.3

0)

Reg

ion

0.05

6

Mid

wes

t18

4(2

4.0)

0.71

(0.2

8)

Nor

thea

st86

(11.

2)0.

62 (0

.32)

Sou

th38

7(5

0.5)

0.66

(0.3

0)

Wes

t10

9(1

4.2)

0.70

(0.2

7)

Phy

sici

an S

pec

ialt

y

Usu

al a

sthm

a ca

re p

hysi

cian

a0.

020

Pul

mon

olog

ist

214

(27.

9)0.

68 (0

.28)

Prim

ary

care

128

(16.

7)0.

64 (0

.31)

Alle

rgis

ts38

1(4

9.7)

0.69

(0.2

9)

Oth

er22

(2.9

)0.

66 (0

.36)

Unk

now

n21

(2.7

)0.

48 (0

.39)

Gen

eral

Co

mo

rbid

itie

s

No

. of

chro

nic

cond

itio

ns (m

ean

4.7;

SD

2.3

)0.

047

1-2

155

(20.

2)0.

63 (0

.33)

3-4

227

(29.

6)0.

69 (0

.29)

5-6

216

(28.

2)0.

71 (0

.27)

7+

168

(21.

9)0.

65 (0

.29)

Cha

rlso

n C

om

orb

idit

y In

dex

7 (m

ean

1.8;

SD

1.7

)0.

967

153

0(6

9.2)

0.68

(0.3

0)

286

(11.

2)0.

68 (0

.29)

3+

150

(19.

6)0.

67 (0

.29)

Evi

den

ce o

f al

lerg

y<

.001

No

57(7

.4)

0.55

(0.3

4)

Yes

709

(92.

6)0.

69 (0

.29)

Res

pir

ato

ry-S

pec

ific

Co

mo

rbid

itie

s

CO

PD

0.33

8

No

577

(75.

3)0.

67 (0

.31)

Yes

189

(24.

7)0.

69 (0

.27)

Sin

usit

is0.

551

No

243

(31.

7)0.

67 (0

.31)

Yes

523

(68.

3)0.

68 (0

.29)

Rhi

niti

s<

0.00

1

No

93(1

2.1)

0.57

(0.3

3)

Yes

673

(87.

9)0.

69 (0

.29)

To

nsill

itis

0.32

1

No

731

(95.

4)0.

67 (0

.30)

Yes

35(4

.6)

0.72

(0.2

8)

Acu

te u

pp

er r

esp

irat

ory

infe

ctio

n0.

471

No

515

(67.

2)0.

67 (0

.30)

Yes

251

(32.

8)0.

69 (0

.28)

Co

njun

ctiv

itis

0.89

4

No

619

(80.

8)0.

68 (0

.30)

Yes

147

(19.

2)0.

67 (0

.29)

Chr

oni

c o

titi

s m

edia

0.00

2

No

746

(97.

4)0.

67 (0

.30)

Yes

20(2

.6)

0.81

(0.1

7)

Nas

al p

oly

po

sis

0.07

3

No

663

(86.

6)0.

68 (0

.29)

Yes

103

(13.

4)0.

63 (0

.32)

Co

ugh

0.42

7

No

381

(49.

7)0.

67 (0

.31)

Yes

385

(50.

3)0.

68 (0

.28)

N(%

)M

PR

M

ean

(SD

)P

Val

ue

All

766

(100

.0)

0.68

(0.3

0)

Ast

hma

Co

ntro

l in

the

Pre

ind

ex P

erio

d

Po

or

asth

ma

cont

rolb

0.09

6

No

191

(24.

9)0.

64 (0

.32)

Yes

575

(75.

1)0.

69 (0

.29)

Ast

hma-

rela

ted

inp

atie

nt h

osp

ital

izat

ion

0.34

0

No

657

(85.

8)0.

68 (0

.30)

Yes

109

(14.

2)0.

65 (0

.30)

Ast

hma-

rela

ted

ED

vis

it0.

412

No

705

(92.

0)0.

67 (0

.30)

Yes

61(8

.0)

0.71

(0.2

9)

Tw

o o

r m

ore

ora

l co

rtic

ost

ero

id p

resc

rip

tio

ns f

illed

0.03

1

No

265

(34.

6)0.

64 (0

.32)

Yes

501

(65.

4)0.

69 (0

.28)

Six

or

mo

re s

hort

-act

ing

bet

a-ag

oni

st p

resc

rip

tio

ns f

illed

0.

310

No

434

(56.

7)0.

67 (0

.30)

Yes

332

(43.

3)0.

69 (0

.29)

EP

R-3

Gui

del

ines

8 T

hera

py

Ste

p in

Pre

ind

ex P

erio

d

The

rap

y st

ep p

rio

r to

init

iati

ng o

mal

izum

ab0.

006

No

asth

ma

med

s68

(8.9

)0.

56 (0

.33)

Ste

p 1

44(5

.7)

0.61

(0.3

2)

Ste

p 2

112

(14.

6)0.

67 (0

.30)

Ste

p 3

121

(15.

8)0.

73 (0

.27)

Ste

p 4

136

(17.

8)0.

69 (0

.28)

Ste

p 5

214

(27.

9)0.

69 (0

.29)

Ste

p 6

37(4

.8)

0.63

(0.3

3)

Unc

lass

ified

34(4

.4)

0.72

(0.2

8)

Med

icat

ion

Rat

ioc

and

Oth

er A

sthm

a M

edic

atio

n U

se in

the

Pre

ind

ex P

erio

d

Med

icat

ion

rati

o (m

ean

0.64

; SD

0.2

8 am

ong

718

pat

ient

s w

ith m

edic

atio

n ra

tios)

0.00

3

Low

rat

io (<

0.5)

197

(25.

7)0.

64 (0

.31)

Hig

h ra

tio (≥

0.5)

521

(68.

0)0.

70 (0

.28)

Mis

sing

(n

o co

ntro

ller

or

rel

ieve

r)48

(6.3

)0.

55 (0

.35)

Sho

rt-a

ctin

g b

eta-

ago

nist

inha

lers

0.04

4

No

115

(15.

0)0.

62 (0

.32)

Yes

651

(85.

0)0.

68 (0

.29)

Ant

icho

liner

gic

s0.

077

No

521

(68.

0)0.

66 (0

.30)

Yes

245

(32.

0)0.

70 (0

.29)

Ora

l co

rtic

ost

ero

ids

0.11

9

No

153

(20.

0)0.

64 (0

.32)

Yes

613

(80.

0)0.

68 (0

.29)

ICS

/LA

BA

co

mb

inat

ion

0.05

1

No

240

(31.

3)0.

64 (0

.31)

Yes

526

(68.

7)0.

69 (0

.29)

ICS

alo

ne

0.28

6

No

450

(58.

7)0.

67 (0

.31)

Yes

316

(41.

3)0.

69 (0

.28)

LAB

A a

lone

0.79

0

No

643

(83.

9)0.

67 (0

.30)

Yes

123

(16.

1)0.

68 (0

.30)

Mas

t ce

ll st

abili

zers

0.10

8

No

734

(95.

8)0.

67 (0

.30)

Yes

32(4

.2)

0.76

(0.2

5)

Met

hylx

anth

ines

0.81

0

No

670

(87.

5)0.

67 (0

.30)

Yes

96(1

2.5)

0.68

(0.2

6)

Leuk

otr

iene

rec

epto

r an

tag

oni

sts

0.07

8

No

221

(28.

9)0.

65 (0

.31)

Yes

545

(71.

1)0.

69 (0

.29)

Tab

le 1

. MP

R o

f Om

aliz

umab

Str

atifi

ed b

y P

atie

nt D

emog

rap

hics

and

Clin

ical

Cha

ract

eris

tics

a The

usu

al a

sthm

a ca

re p

hysi

cian

was

det

erm

ined

by

the

larg

est

plu

ralit

y of

offi

ce v

isits

with

eva

luat

ion

and

m

anag

emen

t se

rvic

es a

nd a

sthm

a d

iagn

osis

. bA

sthm

a-re

late

d in

pat

ient

hos

pita

lizat

ion,

ast

hma-

rela

ted

ED

vis

it, ≥

2 or

al c

ortic

oste

roid

pre

scrip

tions

fille

d,

or ≥

6 sh

ort-

actin

g b

eta-

agon

ist

pre

scrip

tions

fille

d.

c Med

icat

ion

ratio

is u

nits

of a

sthm

a co

ntro

llers

to

units

of c

ontr

olle

rs +

uni

ts o

f rel

ieve

rs.

CO

PD

= c

hron

ic o

bst

ruct

ive

pul

mon

ary

dis

ease

; ED

= e

mer

genc

y d

epar

tmen

t; E

PR

-3 =

Nat

iona

l Ast

hma

Ed

ucat

ion

and

Pre

vent

ion

Pro

gram

Exp

ert

Pan

el R

epor

t 3;

ICS

= in

hale

d c

ortic

oste

roid

; LA

BA

= lo

ng-a

ctin

g b

eta-

agon

ist;

MP

R =

med

icat

ion

pos

sess

ion

ratio

.

Om

aliz

umab

New

Use

rs(N

=76

6)M

PR

(Ran

ge 0

-1)

Mea

n (S

D)

0.68

(0.3

0)[M

edia

n][0

.80]

Dis

cont

inue

d o

mal

izum

ab

n (%

)34

7 (4

5.3)

Day

s to

dis

cont

inua

tion/

end

of s

tud

yM

ean

(SD

)25

6.5

(131

.6)

[Med

ian]

[353

]N

umb

er o

f om

aliz

umab

cla

ims

Mea

n (S

D)

10.1

(5.4

)[M

edia

n][1

1]1

n (%

)64

(8.4

)2-

5n

(%)

94 (1

2.3)

6-11

n (%

)24

9 (3

2.5)

12+

n (%

)35

9 (4

6.9)

Tab

le 3

. Om

aliz

umab

Use

in t

he P

ostin

dex

Per

iod

HR

(

95%

CI)

P V

alue

Ag

e, y

12-

17 v

s 65

+0.

82(0

.41

- 1.

67)

0.57

6 1

8-34

vs

65+

1.15

(0.6

4 -

2.16

)0.

655

35-

44 v

s 65

+0.

86(0

.50

- 1.

57)

0.60

0 4

5-54

vs

65+

0.81

(0.4

8 -

1.46

)0.

457

55-

64 v

s 65

+0.

76(0

.44

- 1.

38)

0.34

4Fe

mal

e vs

mal

e0.

83(0

.66

- 1.

05)

0.12

1R

egio

n M

idw

est

vs W

est

0.76

(0.5

2 -

1.12

)0.

164

Nor

thea

st v

s W

est

0.98

(0.6

3 -

1.51

)0.

917

Sou

th v

s W

est

1.16

(0.8

4 -

1.62

)0.

380

Usu

al a

sthm

a ca

re p

hysi

cian

sp

ecia

lty

Alle

rgis

t vs

prim

ary/

othe

r0.

85(0

.64

- 1.

13)

0.26

4 P

ulm

onol

ogis

t vs

prim

ary/

othe

r0.

84(0

.62

- 1.

14)

0.27

3N

o. o

f ch

roni

c co

ndit

ions

1-2

vs

7+0.

89(0

.59

- 1.

35)

0.59

6 3

-4 v

s 7+

0.81

(0.5

8 -

1.13

)0.

212

5-6

vs

7+0.

69(0

.51

- 0.

94)

0.02

0E

vid

ence

of

alle

rgy

0.97

(0.5

3 -

1.71

)0.

914

The

rap

y st

ep N

o as

thm

a m

edic

atio

n vs

Ste

p 6

1.25

(0.6

4 -

2.49

)0.

518

Ste

p 1

vs

Ste

p 6

1.21

(0.6

1 -

2.44

)0.

580

Ste

p 2

vs

Ste

p 6

1.18

(0.6

9 -

2.13

)0.

560

Ste

p 3

vs

Ste

p 6

0.79

(0.4

6 -

1.44

)0.

430

Ste

p 4

vs

Ste

p 6

0.92

(0.5

4 -

1.66

)0.

769

Ste

p 5

vs

Ste

p 6

0.90

(0.5

4 -

1.58

)0.

689

Unc

lass

ified

vs

Ste

p 6

0.73

(0.3

3 -

1.59

)0.

437

Med

icat

ion

rati

o L

ow r

atio

(<0.

5) v

s hi

gh r

atio

(≥0.

5)1.

18(0

.66

- 2.

07)

0.56

3 M

issi

ng (n

o co

ntro

ller

or r

elie

ver)

vs

high

rat

io (≥

0.5)

1.36

(0.7

7 -

2.43

)0.

289

CO

PD

0.93

(0.7

1 -

1.22

)0.

613

Sin

usit

is0.

99(0

.77

- 1.

27)

0.91

6R

hini

tis

0.65

(0.4

0 -

1.09

)0.

082

To

nsill

itis

0.58

(0.2

9 -

1.02

)0.

083

Acu

te u

pp

er r

esp

irat

ory

infe

ctio

n1.

12(0

.88

- 1.

42)

0.34

1C

onj

unct

ivit

is1.

13(0

.85

- 1.

49)

0.38

4C

hro

nic

oti

tis

med

ia0.

61(0

.26

- 1.

24)

0.21

8N

asal

po

lyp

osi

s1.

46(1

.05

- 2.

00)

0.01

9C

oug

h0.

95(0

.75

- 1.

19)

0.62

7D

isea

ses

of

the

circ

ulat

ory

sys

tem

1.32

(1.0

0 -

1.76

)0.

052

Tab

le 4

. Ris

k of

Dis

cont

inui

ng O

mal

izum

ab: A

dju

sted

Haz

ard

Rat

ios

and

95

% C

onfid

ence

Inte

rval

s

CI =

con

fiden

ce in

terv

al; H

R =

haz

ard

rat

io.

Co

effic

ient

SE

P V

alue

Inte

rcep

t0.

490.

10<

0.00

1A

ge,

y 1

2-17

vs

65+

0.04

0.07

0.56

7 1

8-34

vs

65+

-0.0

40.

060.

520

35-

44 v

s 65

+0.

010.

060.

845

45-

54 v

s 65

+0.

040.

060.

483

55-

64 v

s 65

+0.

060.

060.

298

Fem

ale

vs m

ale

0.03

0.02

0.26

8R

egio

n M

idw

est

vs W

est

0.03

0.04

0.37

5 N

orth

east

vs

Wes

t-0

.03

0.04

0.54

5 S

outh

vs

Wes

t-0

.03

0.03

0.29

0U

sual

ast

hma

care

phy

sici

an s

pec

ialt

y A

llerg

ist

vs p

rimar

y/ot

her

0.04

0.03

0.17

8 P

ulm

onol

ogis

t vs

prim

ary/

othe

r0.

040.

030.

193

No

. of

chro

nic

cond

itio

ns 1

-2 v

s 7+

-0.0

30.

040.

522

3-4

vs

7+0.

030.

030.

334

5-6

vs

7+0.

070.

030.

028

Evi

den

ce o

f al

lerg

y0.

060.

060.

351

The

rap

y st

ep N

o as

thm

a m

edic

atio

n vs

Ste

p 6

-0.0

20.

070.

818

Ste

p 1

vs

Ste

p 6

-0.0

10.

070.

933

Ste

p 2

vs

Ste

p 6

0.01

0.06

0.81

7 S

tep

3 v

s S

tep

60.

080.

060.

138

Ste

p 4

vs

Ste

p 6

0.04

0.05

0.50

6 S

tep

5 v

s S

tep

60.

040.

050.

443

Unc

lass

ified

vs

Ste

p 6

0.10

0.07

0.18

2M

edic

atio

n ra

tio

Low

rat

io (<

0.5)

vs

high

rat

io (≥

0.5)

-0.0

30.

060.

602

Mis

sing

(no

cont

rolle

r or

rel

ieve

r)

vs

high

rat

io (≥

0.5)

-0.0

80.

060.

211

CO

PD

0.03

0.03

0.31

7S

inus

itis

0.00

0.02

0.92

7R

hini

tis

0.08

0.05

0.11

2T

ons

illit

is0.

070.

050.

178

Acu

te u

pp

er r

esp

irat

ory

infe

ctio

n0.

000.

020.

950

Co

njun

ctiv

itis

-0.0

20.

030.

477

Chr

oni

c o

titi

s m

edia

0.13

0.07

0.05

0N

asal

po

lyp

osi

s-0

.09

0.03

0.00

5C

oug

h0.

010.

020.

684

Dis

ease

s o

f th

e ci

rcul

ato

ry s

yste

m-0

.07

0.03

0.00

8

Tab

le 2

. Mul

tivar

iate

Ana

lysi

s: C

hara

cter

istic

s A

ssoc

iate

d W

ith

Om

aliz

umab

MP

R

CO

PD

= c

hron

ic o

bst

ruct

ive

pul

mon

ary

dis

ease

; MP

R =

med

icat

ion

pos

sess

ion

ratio

.

This

stu

dy

was

sup

por

ted

by

Gen

ente

ch, I

nc.,

Sou

th S

an F

ranc

isco

, CA

, and

Nov

artis

P

harm

aceu

tical

s C

orp

orat

ion,

Eas

t H

anov

er, N

J, a

nd t

hird

-par

ty w

ritin

g as

sist

ance

for

this

pos

ter

was

pro

vid

ed b

y G

enen

tech

, Inc

., S

outh

San

Fra

ncis

co C

A, a

nd N

ovar

tis

Pha

rmac

eutic

als,

Eas

t H

anov

er, N

J.

Characteristics Associated With Medication Adherence Among New Omalizumab Users46

James Zazzali, PhD, MPH1; Michael S. Broder, MD, MSHS2; Eunice Chang, PhD2 1Genentech Inc., South San Francisco, CA; 2Partnership for Health Analytic Research, Beverly Hills, CA

ABSTRACTOBJECTIVE: Adherence to omalizumab (OMA) therapy has not been well studied. We sought to identify characteristics associated with adherence among new OMA users. METHODS: This was a retrospective cohort analysis using a HIPAA-compliant claims database. The study identified asthma patients who were ≥12 years old, newly treated with OMA between 7/1/2004 and 6/30/2007, and enrolled for 1 year before and 1 year after the first OMA claim. Adherence was measured by medication possession ratio (MPR) (total days of medication supplied ÷ 365) with each OMA claim considered a 28-day supply. Therapy step, as defined by the EPR3 guidelines, was assigned using a published algorithm. A base linear regression model was conducted with MPR as the dependent variable and demographics, physician specialty, respiratory comorbidities, asthma control, therapy step, and medication ratio forced into the model as independent variables. Other comorbidities were considered with forward selection and retained if significant at p<.05.RESULTS: We identified 766 new OMA users; mean age was 43 (SD 14) years, and 61% (n=466) were female. Forty-two percent of patients had allergists as their usual source of care, 20% pulmonologists, 28.3% primary care physicians, and the remainder other/unspecified. The mean number of chronic conditions was 5 (SD 2). Before starting OMA, most of patients were on EPR3 Step 5 therapy (28%), followed by Step 4 (18%), Step 3 (16%), Step 2 (15%), Step 1 (6%), and Step 6 (5%). Mean MPR in the year after treatment initiation was 0.68 (SD 0.30), and 55% persisted with therapy for at least 1 year. The final model included the base variables and diseases of circulatory system (the only additional significant predictor). Significant predictors of higher MPR were: care provided by allergists or pulmonologists, chronic otitis media, 5 or 6 vs ≥7 chronic conditions, and no disease of the circulatory system.CONCLUSIONS: We found MPR for omalizumab to be higher on average than what has been reported for combination corticosteroid/long-acting beta-agonist therapy. Care by an allergist or pulmonologist was associated with greater adherence. Confounding by disease severity is possible, but the relationship was significant after controlling for therapy step. If this finding is confirmed in other studies, it supports the value of specialist care for patients with difficult to treat asthma.

CONCLUSIONS• Among new omalizumab users, we estimated the MPR to be 0.68 with 54.7%

persisting on omalizumab at one year after initiating therapy.

• Omalizumab adherence and persistence are consistent with previously published reports, although this analysis indicates slightly higher estimates.

• The number of chronic conditions and select respiratory comorbidities were significant predictors of adherence and persistence in our multivariate models.

LIMITATIONS• Administrative claims data do not indicate the dosing schedule for omalizumab;

in this analysis, each dose of omalizumab was assumed to be a 28 day supply.

• Inclusion of concomitant asthma medications as covariates is indicative only of those medications filled and not reflective of patient adherence to therapy.

BACKGROUND• Lack of adherence to prescribed treatments for asthma is a well-known problem.

Rates of nonadherence range from 30% to 70%.1-3

• Poor asthma medication adherence is associated with decreases in asthma control and increases in emergency department visits, hospitalizations, and the need for oral corticosteroids.3,4

• Omalizumab, a humanized monoclonal antibody targeting immunoglobulin E, is approved in the United States for the treatment of adults and adolescents (≥12 years) with moderate to severe persistent allergic asthma that is inadequately controlled with inhaled corticosteroids.5

• Adherence to omalizumab therapy has not been well studied. One prior analysis of asthma patients newly treated with omalizumab estimated adherence rates to be 64.6% with 54% persisting up to one year.6

OBJECTIVE• To identify characteristics associated with adherence and persistence among new

omalizumab users

METHODSStudy Design• A retrospective cohort analysis using a HIPAA-compliant administrative claims

database of 10 million covered lives representing all major regions of the United States.

• Eligible patients were ≥12 years old, diagnosed with asthma, newly treated with omalizumab between 7/1/2004 and 6/30/2007, and followed for a year (Figures 1 and 2).

RESULTS• We identified 766 new omalizumab users; average age was 43.4 years and 61%

were female. Fifty percent of patients received asthma care from an allergist, 28% a pulmonologist, and 17% a primary care physician.

• Overall, the MPR was 0.68 (SD, ± 0.30). MPR stratified by baseline measures are presented in Table 1 and results of the multivariate analysis in Table 2.

• During follow-up, 45.3% of patients discontinued treatment. Mean (SD) time to discontinuation/end of study was 256.5 (131.6) days; median was 353 days (Table 3, Figure 3).

• The risk of discontinuing omalizumab was examined across a number of variables (Table 4).

REFERENCES1. Bender B et al. Ann Allergy Asthma Immunol. 2000;

85(5):416-421.2. Bender BG et al. Ann Allergy Asthma Immunol. 2007;

98(4):322-328.3. World Health Organization. Adherence to long-term

therapies: evidence for action. Geneva, Switzerland: World Health Organization; 2003.

4. Williams LK et al. J Allergy Clin Immunol. 2004;114(6):1288-1293.

5. Xolair [prescribing information]. South San Francisco, CA: Genentech USA, Inc.; 2010.

6. Broder MS et al. Allergy Asthma Proc. 2009;30(2):148-157.7. Deyo RA et al. J Clin Epidemiol. 1992;45(6):613-619.8. National Asthma Education and Prevention Program. Expert

Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007;120(5 suppl):S94-S138.

Index Date

First claim for omalizumab in ID period

1-year period (Preindex period)

7/1/03 6/30/08

6/30/077/1/04

Identification (ID) Period

1-year period (Postindex period)

Figure 1. Study Timeline

% o

f P

atie

nts

on

Tre

atm

ent

Days to Discontinue Omalizumab

100

75

50

25

0

0 50 100 150 200 250 300 350 400

Figure 3. Days to Discontinuation of Omalizumab.

Study Outcomes• Adherence to omalizumab therapy during the postindex period, as measured by the

medication possession ratio (MPR) – Calculated as the total days of medication supplied over the year, divided by 365 – Each omalizumab claim was considered a 28-day supply • Medication persistence during the postindex period, as measured by time

to discontinuation – Calculated as the number of days on omalizumab with no gaps of more than

45 daysStatistical Analysis• To evaluate the association of baseline measures (patient demographic and clinical

characteristics) with omalizumab adherence and persistence, we conducted a linear regression model with adherence (MPR) as the continuous dependent variable and all baseline measures as independent variables and a similar logistic regression model to predict persistence at one year.

– Based on bivariate analysis results and clinical relevance, demographics (age, sex, and region), asthma physician specialty, number of chronic conditions, evidence of allergy, respiratory-specific comorbidities, therapy step, and medication ratio were first included in the linear regression model; we then used forward selection to identify significant results for other baseline measures.

3456 patients with a claim of omalizumab in ID period

(7/1/2004–6/30/2007)

n=3391

n=3377

n=2886

n=766

65 patients with age <12 years on the index date (the date of �rst omalizumab claim in ID period)

14 patients had no asthma diagnosis in the preindex or postindex period

491 previously used omalizumab

2120 patients were not continuously enrolled in the preindex and postindex periods

Figure 2. Cohort Selection for Omalizumab New Users.

ID = identification.

N (%)MPR

Mean (SD) P Value

All 766 (100.0) 0.68 (0.30)

Demographics

Age, y (mean 43.4; SD 14.5) 0.157

12-17 68 (8.9) 0.72 (0.28)

18-34 111 (14.5) 0.62 (0.34)

35-44 183 (23.9) 0.66 (0.30)

45-54 234 (30.5) 0.68 (0.30)

55-64 141 (18.4) 0.71 (0.27)

65+ 29 (3.8) 0.65 (0.24)

Sex 0.174

Female 466 (60.8) 0.69 (0.30)

Male 300 (39.2) 0.66 (0.30)

Region 0.056

Midwest 184 (24.0) 0.71 (0.28)

Northeast 86 (11.2) 0.62 (0.32)

South 387 (50.5) 0.66 (0.30)

West 109 (14.2) 0.70 (0.27)

Physician Specialty

Usual asthma care physiciana 0.020

Pulmonologist 214 (27.9) 0.68 (0.28)

Primary care 128 (16.7) 0.64 (0.31)

Allergists 381 (49.7) 0.69 (0.29)

Other 22 (2.9) 0.66 (0.36)

Unknown 21 (2.7) 0.48 (0.39)

General Comorbidities

No. of chronic conditions (mean 4.7; SD 2.3) 0.047

1-2 155 (20.2) 0.63 (0.33)

3-4 227 (29.6) 0.69 (0.29)

5-6 216 (28.2) 0.71 (0.27)

7+ 168 (21.9) 0.65 (0.29)

Charlson Comorbidity Index7 (mean 1.8; SD 1.7) 0.967

1 530 (69.2) 0.68 (0.30)

2 86 (11.2) 0.68 (0.29)

3+ 150 (19.6) 0.67 (0.29)

Evidence of allergy <.001

No 57 (7.4) 0.55 (0.34)

Yes 709 (92.6) 0.69 (0.29)

Respiratory-Specific Comorbidities

COPD 0.338

No 577 (75.3) 0.67 (0.31)

Yes 189 (24.7) 0.69 (0.27)

Sinusitis 0.551

No 243 (31.7) 0.67 (0.31)

Yes 523 (68.3) 0.68 (0.29)

Rhinitis <0.001

No 93 (12.1) 0.57 (0.33)

Yes 673 (87.9) 0.69 (0.29)

Tonsillitis 0.321

No 731 (95.4) 0.67 (0.30)

Yes 35 (4.6) 0.72 (0.28)

Acute upper respiratory infection 0.471

No 515 (67.2) 0.67 (0.30)

Yes 251 (32.8) 0.69 (0.28)

Conjunctivitis 0.894

No 619 (80.8) 0.68 (0.30)

Yes 147 (19.2) 0.67 (0.29)

Chronic otitis media 0.002

No 746 (97.4) 0.67 (0.30)

Yes 20 (2.6) 0.81 (0.17)

Nasal polyposis 0.073

No 663 (86.6) 0.68 (0.29)

Yes 103 (13.4) 0.63 (0.32)

Cough 0.427

No 381 (49.7) 0.67 (0.31)

Yes 385 (50.3) 0.68 (0.28)

N (%)MPR

Mean (SD) P Value

All 766 (100.0) 0.68 (0.30)

Asthma Control in the Preindex Period

Poor asthma controlb 0.096

No 191 (24.9) 0.64 (0.32)

Yes 575 (75.1) 0.69 (0.29)

Asthma-related inpatient hospitalization 0.340

No 657 (85.8) 0.68 (0.30)

Yes 109 (14.2) 0.65 (0.30)

Asthma-related ED visit 0.412

No 705 (92.0) 0.67 (0.30)

Yes 61 (8.0) 0.71 (0.29)

Two or more oral corticosteroid prescriptions filled 0.031

No 265 (34.6) 0.64 (0.32)

Yes 501 (65.4) 0.69 (0.28)

Six or more short-acting beta-agonist prescriptions filled 0.310

No 434 (56.7) 0.67 (0.30)

Yes 332 (43.3) 0.69 (0.29)

EPR-3 Guidelines8 Therapy Step in Preindex Period

Therapy step prior to initiating omalizumab 0.006

No asthma meds 68 (8.9) 0.56 (0.33)

Step 1 44 (5.7) 0.61 (0.32)

Step 2 112 (14.6) 0.67 (0.30)

Step 3 121 (15.8) 0.73 (0.27)

Step 4 136 (17.8) 0.69 (0.28)

Step 5 214 (27.9) 0.69 (0.29)

Step 6 37 (4.8) 0.63 (0.33)

Unclassified 34 (4.4) 0.72 (0.28)

Medication Ratioc and Other Asthma Medication Use in the Preindex Period

Medication ratio (mean 0.64; SD 0.28 among 718 patients with medication ratios) 0.003

Low ratio (<0.5) 197 (25.7) 0.64 (0.31)

High ratio (≥0.5) 521 (68.0) 0.70 (0.28)

Missing (no controller or reliever)

48 (6.3) 0.55 (0.35)

Short-acting beta-agonist inhalers 0.044

No 115 (15.0) 0.62 (0.32)

Yes 651 (85.0) 0.68 (0.29)

Anticholinergics 0.077

No 521 (68.0) 0.66 (0.30)

Yes 245 (32.0) 0.70 (0.29)

Oral corticosteroids 0.119

No 153 (20.0) 0.64 (0.32)

Yes 613 (80.0) 0.68 (0.29)

ICS/LABA combination 0.051

No 240 (31.3) 0.64 (0.31)

Yes 526 (68.7) 0.69 (0.29)

ICS alone 0.286

No 450 (58.7) 0.67 (0.31)

Yes 316 (41.3) 0.69 (0.28)

LABA alone 0.790

No 643 (83.9) 0.67 (0.30)

Yes 123 (16.1) 0.68 (0.30)

Mast cell stabilizers 0.108

No 734 (95.8) 0.67 (0.30)

Yes 32 (4.2) 0.76 (0.25)

Methylxanthines 0.810

No 670 (87.5) 0.67 (0.30)

Yes 96 (12.5) 0.68 (0.26)

Leukotriene receptor antagonists 0.078

No 221 (28.9) 0.65 (0.31)

Yes 545 (71.1) 0.69 (0.29)

Table 1. MPR of Omalizumab Stratified by Patient Demographics and Clinical Characteristics

aThe usual asthma care physician was determined by the largest plurality of office visits with evaluation and management services and asthma diagnosis. bAsthma-related inpatient hospitalization, asthma-related ED visit, ≥2 oral corticosteroid prescriptions filled, or ≥6 short-acting beta-agonist prescriptions filled.cMedication ratio is units of asthma controllers to units of controllers + units of relievers.COPD = chronic obstructive pulmonary disease; ED = emergency department; EPR-3 = National Asthma Education and Prevention Program Expert Panel Report 3; ICS = inhaled corticosteroid; LABA = long-acting beta-agonist; MPR = medication possession ratio.

Omalizumab New Users(N=766)

MPR (Range 0-1) Mean (SD) 0.68 (0.30)[Median] [0.80]

Discontinued omalizumab n (%) 347 (45.3)Days to discontinuation/end of study Mean (SD) 256.5 (131.6)

[Median] [353]Number of omalizumab claims Mean (SD) 10.1 (5.4)

[Median] [11]1 n (%) 64 (8.4)2-5 n (%) 94 (12.3)6-11 n (%) 249 (32.5)12+ n (%) 359 (46.9)

Table 3. Omalizumab Use in the Postindex Period

HR (95% CI) P ValueAge, y 12-17 vs 65+ 0.82 (0.41 - 1.67) 0.576 18-34 vs 65+ 1.15 (0.64 - 2.16) 0.655 35-44 vs 65+ 0.86 (0.50 - 1.57) 0.600 45-54 vs 65+ 0.81 (0.48 - 1.46) 0.457 55-64 vs 65+ 0.76 (0.44 - 1.38) 0.344Female vs male 0.83 (0.66 - 1.05) 0.121Region Midwest vs West 0.76 (0.52 - 1.12) 0.164 Northeast vs West 0.98 (0.63 - 1.51) 0.917 South vs West 1.16 (0.84 - 1.62) 0.380Usual asthma care physician specialty Allergist vs primary/other 0.85 (0.64 - 1.13) 0.264 Pulmonologist vs primary/other 0.84 (0.62 - 1.14) 0.273No. of chronic conditions 1-2 vs 7+ 0.89 (0.59 - 1.35) 0.596 3-4 vs 7+ 0.81 (0.58 - 1.13) 0.212 5-6 vs 7+ 0.69 (0.51 - 0.94) 0.020Evidence of allergy 0.97 (0.53 - 1.71) 0.914Therapy step No asthma medication vs Step 6 1.25 (0.64 - 2.49) 0.518 Step 1 vs Step 6 1.21 (0.61 - 2.44) 0.580 Step 2 vs Step 6 1.18 (0.69 - 2.13) 0.560 Step 3 vs Step 6 0.79 (0.46 - 1.44) 0.430 Step 4 vs Step 6 0.92 (0.54 - 1.66) 0.769 Step 5 vs Step 6 0.90 (0.54 - 1.58) 0.689 Unclassified vs Step 6 0.73 (0.33 - 1.59) 0.437Medication ratio Low ratio (<0.5) vs high ratio (≥0.5) 1.18 (0.66 - 2.07) 0.563 Missing (no controller or reliever) vs high ratio (≥0.5) 1.36 (0.77 - 2.43) 0.289COPD 0.93 (0.71 - 1.22) 0.613Sinusitis 0.99 (0.77 - 1.27) 0.916Rhinitis 0.65 (0.40 - 1.09) 0.082Tonsillitis 0.58 (0.29 - 1.02) 0.083Acute upper respiratory infection 1.12 (0.88 - 1.42) 0.341Conjunctivitis 1.13 (0.85 - 1.49) 0.384Chronic otitis media 0.61 (0.26 - 1.24) 0.218Nasal polyposis 1.46 (1.05 - 2.00) 0.019Cough 0.95 (0.75 - 1.19) 0.627Diseases of the circulatory system 1.32 (1.00 - 1.76) 0.052

Table 4. Risk of Discontinuing Omalizumab: Adjusted Hazard Ratios and 95% Confidence Intervals

CI = confidence interval; HR = hazard ratio.

Coefficient SE P ValueIntercept 0.49 0.10 <0.001Age, y 12-17 vs 65+ 0.04 0.07 0.567 18-34 vs 65+ -0.04 0.06 0.520 35-44 vs 65+ 0.01 0.06 0.845 45-54 vs 65+ 0.04 0.06 0.483 55-64 vs 65+ 0.06 0.06 0.298Female vs male 0.03 0.02 0.268Region Midwest vs West 0.03 0.04 0.375 Northeast vs West -0.03 0.04 0.545 South vs West -0.03 0.03 0.290Usual asthma care physician specialty Allergist vs primary/other 0.04 0.03 0.178 Pulmonologist vs primary/other 0.04 0.03 0.193No. of chronic conditions 1-2 vs 7+ -0.03 0.04 0.522 3-4 vs 7+ 0.03 0.03 0.334 5-6 vs 7+ 0.07 0.03 0.028Evidence of allergy 0.06 0.06 0.351Therapy step No asthma medication vs Step 6 -0.02 0.07 0.818 Step 1 vs Step 6 -0.01 0.07 0.933 Step 2 vs Step 6 0.01 0.06 0.817 Step 3 vs Step 6 0.08 0.06 0.138 Step 4 vs Step 6 0.04 0.05 0.506 Step 5 vs Step 6 0.04 0.05 0.443 Unclassified vs Step 6 0.10 0.07 0.182Medication ratio Low ratio (<0.5) vs high ratio (≥0.5) -0.03 0.06 0.602 Missing (no controller or reliever) vs high ratio (≥0.5)

-0.08 0.06 0.211

COPD 0.03 0.03 0.317Sinusitis 0.00 0.02 0.927Rhinitis 0.08 0.05 0.112Tonsillitis 0.07 0.05 0.178Acute upper respiratory infection 0.00 0.02 0.950Conjunctivitis -0.02 0.03 0.477Chronic otitis media 0.13 0.07 0.050Nasal polyposis -0.09 0.03 0.005Cough 0.01 0.02 0.684Diseases of the circulatory system -0.07 0.03 0.008

Table 2. Multivariate Analysis: Characteristics Associated With Omalizumab MPR

COPD = chronic obstructive pulmonary disease; MPR = medication possession ratio.

This study was supported by Genentech, Inc., South San Francisco, CA, and Novartis Pharmaceuticals Corporation, East Hanover, NJ, and third-party writing assistance for this poster was provided by Genentech, Inc., South San Francisco CA, and Novartis Pharmaceuticals, East Hanover, NJ.

46 characteristics associated with medication adherence … · 2019-11-22 · 46 characteristics...

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