ganesh raghu, md, fccp, facpeng).pdf · g raghu*,1 ja lasky,2 u costabel*,3 kk brown*,4 v cottin,5...
TRANSCRIPT
Ganesh Raghu, MD, FCCP, FACP
Professor of Medicine and Laboratory Medicine (Adjunct)University of Washington, Seattle, WA, USA
Chief, Chest ClinicDirector, Interstitial Lung Disease, Sarcoid and
Pulmonary Fibrosis ProgramMedical Director, Lung Transplant ProgramUniversity of Washington Medical Center
Seattle, WA, USA
Interstitial lung disease
Medical Treatment -current trends
Interstitial Lung Disease(Immunocompetent Host)
Interstitial Lung Disease
Iatrogenic/Drug-induced
Conditions
Granulo-matous
Diseases**
Occupational/Environmental
Exposures
InheritedConditions***
UniqueEntities*
Collagen-VascularDiseases
Idiopathic InterstitialPneumonia (IIP)
* Langerhans’ cell granulomatosis, lymphangioleimyomatosis, alveolar proteinosis, idiopathic pulmonary capillaritis
** Sarcoidosis, hypersensitivity pneumonitis*** Tuberous sclerosis, Hermansky-Pudlak Syndrome, neruofibromatosis, metabolic storage
disorders, familial IPF
Interstitial Lung Disease(Immunocompetent Host)
Idiopathic InterstitialPneumonia (IIP)
Idiopathic PulmonaryFibrosis (UIP)
Non-IPFIIP
RBILD(DIP)
COP(BOOP)
NSIP AIP Eosinophilicpneumonia
LIP
Interstitial Lung DiseaseClinical Response to Currently Available Therapeutic Agents
● Sarcoidosis● Acute hypersensitivity pneumonitis● Drug induced (acute)● Environmental● Acute pulmonary capillaritis● Idiopathic BOOP● Respiratory bronchiolitis associated ILD● Chronic eosinophilic pneumonia● Primary alveolar proteinosis● Acute radiation pneumonitis● Lymphocytic interstitial pneumonia
Generally Favorable
Interstitial Lung DiseaseClinical Response to Currently Available Therapeutic Agents
● IPF● Chronic secondary, and advanced pulmonary fibrosis● Pulmonary fibrosis co-existing/associated with pulm.
HTN● Chronic idiopathic BOOP (subset of idiopathic BOOP)● BOOP associated with collagen vascular diseases● Chronic pulmonary hemorrhage syndromes● Pulmonary venoocclusive disease
Generally Unfavorable
Interstitial Lung DiseaseClinical Response to Currently Available Therapeutic Agents
● Obliterative bronchiolitis with or without associated ILD
● Acute interstitial pneumonia of unknown etiology● Langerhan cell granulomatosis● Lymphangioleiomyomatosis● Tuberous sclerosis● Pulmonary fibrosis associated with other inherited
disorders● Familial idiopathic pulmonary fibrosis
Generally Unfavorable
Idiopathic Interstitial Pneumonia (IIP)
NSIP LIP COP RBILD DIP AIPEosinophilicpneumonia
Steroid response (vast majority)
NSIP-f NSIP-c
IPF (UIP)
IIP
Non-IPF
Death (~ 3 years)
RelentlesslyProgressive
Subgroup
Subgroup (small)
Slow progression (+ adjunct immunosuppressive)
Death (several years ?)
Idiopathic Pulmonary Fibrosis:Clinical Course/Subgroups*
IPF
Slowlyprogressive
Respiratoryinsufficiency
Cor pulmonale
Acutedeterioration
(? exacerbation)
Stable
Slowlyprogressive
Progressionslowed by Rx
Cor pulmonale(2° Pulm hypertension)
(2° Pulm hypertension)
Death
Progressive
Death
Death
Modified from Raghu: Chest 1987; 92:148-54
Deathsecondary toother cause
RapidlyProgressive
Continuedprogression
RxComplication
? trigger
Respiratoryinsufficiency
● Usual course:– Often insidious– Relentlessly progressive– No spontaneous remissions
● Treatment:– No data to support specific therapy, duration,
dosage, timing– Combined corticosteroids and azathioprine or
cyclophosphamide in all patients who do not have contraindications
– Initiate ‘early’ in the clinical course
Treatment
Idiopathic Pulmonary Fibrosis-ATS Statement
Guidelines for Diagnosis and Treatment
AJRCCM Feb 2000
● 6 Months minimum, in the absence of complications or adverse effects
Treatment: Duration
Idiopathic Pulmonary Fibrosis- ATS Statement
Guidelines for Diagnosis and Treatment
At 6 months and 12 months
Improved Stable Worse
Continue therapyContinue low dose prednisoneSwitch to alternative therapy or different cytotoxic Rx or stop Rx
AJRCCM Feb 2000
Idiopathic Pulmonary fibrosis-predictors of survival
● Dyspnea score(1,6)● CRP score (2)● Composite physiologic index (3,4)● Change in PFTs [FVC,DLCO,P(A-a)O2] (5,6)● Walk test - 6 min walk (7)
- modified [ timed walk test-(8) ]distance/velocity to desaturate
1)Schwartz et al,1994; 2)Watters et al,1986; 3)Wells et al,2003;4) Latsi et al,2003;5) Flaherty et al,2003; 6)Collard etal,2003; 7) Lama et al,2003 ;8) Hallstrand et al,2005
Longstanding “Awareness”● Currently available treatment
regimen “ineffective”
● Myth or fact?
Idiopathic Pulmonary Fibrosis Treatment
Idiopathic Pulmonary FibrosisRole of Pilot Studies
“Pilot” Studies – Initial study following an anecdotal observation
RetrospectiveCase Reports/Series
Prospective Data Gathering
Observations: provocative, positive, suggestive
Concepts, Hypothesis
Further Clinical Studies (Prospective)
Idiopathic Pulmonary Fibrosis: TreatmentRole of Pilot Studies
“Pilot” Studies with Positive Observations
Prospective Clinical Studies
Open LabelPhase II
Randomized Control Trials (RCT)
Positive Data
Proof of Concept Phase II
Idiopathic Pulmonary Fibrosis: TreatmentPilot Studies Evolution to Clinical Trials
Well Designed, Phase III RCT
Endpoints for Improved Outcome
Positive 1° Endpoint
Clinical Relevance and Significance
Positive Data
Evidence
Negative 2° and Negative Signals in Subgroups, Exploratory Analysis
Negative 1° Endpoint
Positive 2° and Positive Signals in
Subgroups &/or Exploratory Analyses No Evidence for Treatment
Idiopathic Pulmonary Fibrosis: Treatment
Pilot Studies → Evolution to Clinical Studies
●Prednisone AzathioprinePrednisone + Azathioprine
Treatment Pilot Further Studies Current Status 1/2007
●Colchicine Douglas 1993
Retrospective Douglas 1997
No evidence for clinical benefit
RCT Prospective Douglas 1998
●N-acetyl Cysteine (NAC)
Behr et al. 1997
Multicenter,DBRCT, IFIGENIA (Europe) prednisone + AZA + NAC vs pred + AZA
FVC and DLCO better with adjunct NAC compared to pred+AZA : ? New standard of care ..need further studies
Winterbauer et al. 1978
Double blind RCT, placebo controlled. Raghu et al 1999
Prednisone + Azathioprine “Std of care”, guided by Int’l Consensus 2000 despite no evidence
Idiopathic Pulmonary Fibrosis: TreatmentPilot Studies → Evolution to Clinical Trials
Treatment Pilot Further Studies Current Status 4/2007
● Pirfenidone Raghu et al. 1999
Phase II double-blind RCT. Azuma et al. 2005.
Phase III completed in Japan;ongoing western world
● Etanercept Niden et al. ATS 2002
Proof of concept, DBRCT, placebo
Results presented Raghu :CHEST,11/05
controlled trial ERS,9/06
Ziesche et al. 1999
Multicenter, double-blind, RCT (DBRCT), placebo controlled GIPF-001 (phase III) Raghu et al. 2004.
DBRCT phase III survival studies completed
● γ-interferon
● Anticoagulation Kubo et al,CHEST
05(RCT)needed ? Treatment role
Need further studies
High Dose N-acetylcysteine in Idiopathic Pulmonary Fibrosis: the IFIGENIA-Trial*
● Multinational, double-blind, randomized, placebo-controlled, parallel-group trial
● Prednisone + Azathioprine + NAC vs. Prednisone + Azathioprine
* Maurits Demedts et al NEJM 2005
High Dose N-acetylcysteine in Idiopathic Pulmonary Fibrosis: the IFIGENIA-Trial*
-0.3
-0.2
-0.1
0
0.1Baseline Endpoint 6m
Endpoint12m
Lite
rs
NACPlacebo
NAC (n=)Placebo (n=)
8075
6360
5551
Primary endpoint : VC (L)
P = 0.02
* Maurits Demedts et al NEJM 2005
High Dose N-acetylcysteine in Idiopathic Pulmonary Fibrosis: the IFIGENIA-Trial*
NAC (n=)Placebo (n=)
7974
5859
4847
-1
-0.5
0
0.5Baseline Endpoint 6m Endpoint 12m
mm
ol/m
in/k
Paa
NACPlacebo
Primary endpoint : DLCO (mmol/min/kPa)
P= 0.003
* Maurits Demedts et al NEJM 2005
Survival within one year
0 50 100 150 200 250 300 350 4000.000.050.100.150.80
0.85
0.90
0.95
1.00
1.05
1.10
PLA group
NAC group
Sur
viva
l fun
ctio
n
Days
NAC PlaceboMortality 9% (7/80) 11% (8/75)Time to death 144* (46-276 days) 71 (57-132)
* Median (quartiles)
Idiopathic Pulmonary Fibrosis: Results of the European Trial (IFIGENIA STUDY)*Prednisone plus Azathioprine +/- N-Acetyl Cysteine (NAC)
*M.Demedts et al,NEJM,2005
* Demedts et al NEJM 2005; 353: 229-42
NAC Placebo
AEn
322
6665334331
n8072
6665333331
Patient%
10090
8886444441
AEn
303
1261
10565544
n7567
1251
10565544
Patient%
10089
1371
13787755
Total number of patientsTotal AE
Blood alkaline phos increasedBlood lactate dehydrogenase inc.Back painRespiratory failureBone marrow toxicityEdemaHeadacheAstheniaInfluenza like illnessMuscle crampTremor
Adverse Events (AE) Occurring in at least 5% of Patients
P=0.03
High Dose N-acetylcysteine in Idiopathic Pulmonary Fibrosis: the IFIGENIA-Trial*
* Demedts et al NEJM,2005
Conclusions
● Therapy with NAC 600 mg TID added to prednisone and azathioprine, preserves VC and DLCO in IPF better than prednisone and azathioprine (standard therapy)
Idiopathic Pulmonary FibrosisTreatment with Antifibrotic Agents
Am J Respir Crit Care Med 1999; 159:1061-9
Idiopathic Pulmonary FibrosisTreatment with Pirfenidone
Idiopathic Pulmonary Fibrosis (IPF)Treatment with Pirfenidone in IPF
Open label, Phase 2, Compassionate Use Study (UWMC, Seattle, WA)(Raghu et al,AJRCCM 1999)
Raghu G et al. AJRCCM 1999
● Arata Azuma, MD (Tokyo)● Toshihiro Nukiwa, MD (Sendai)● Eiyasuu Tsuboi, MD (Tokyo)● Moritaka Suga, MD (Kumamoto)● Shosaku Abe, MD (Sapporo)● Koichiro-Nakata, MD (Tokyo)
Idiopathic Pulmonary Fibrosis:Treatment with Pirfenidone (prospective,double blind placebo
controlled,clinical trial in Japan)*
*Sponsor: Shionogi & Co., Ltd. Osaka, JapanAzuma et al,AJRCCM,2005
● Yoshio Taguchi, MD (Tenri)● Sonoko Nagai, MD (Kyoto)● Harumi Itoh, MD (Fukui)● Motoharu Ohi, MD (Osaka)● Atsuhiko Sato, MD (Kyoto)● Shoji Kudoh, MD (Tokyo)
● Ganesh Raghu, MD (Seattle, WA, USA)
Pirfenidone: Treatment for IPFDouble-Blind, Placebo Controlled Clinical Trial in Japan*
I. Primary Endpoint● Lowest SpO2 during 6MET higher in the
subset of pirfenidone group of patients completing the 6 minute walk at 6 months (p=0.0069), 9 months (p=0.0305)- a positive trend(p =0.07) was seen in
all the patients in the pirfenidonegroup(full analysis set)
Results
Azuma et al. AJRCCM (2005)
Pirfenidone treatment in IPF : Current Status(April 2007)
● Experimental anti fibrotic agent
● Only available for use in patients enrolled/participating in clinical studies and not for routine use in patients
● Phase III study began last Nov 2005 in Japan-results announced as a press release by Shionogi(Dec 21st
2006) indicates a positive study(final results for scientific review awaited)
● Phase III study in North America and Europe just begun
● Until results of these studies are available for the scientific community,unknown if effective for IPF
A Randomized Placebo-Controlled Trial Assessing the Efficacy and Safety of Etanercept in Patients with Idiopathic
Pulmonary Fibrosis
Data presented at CHEST : Nov,2005 and at ERS,Sep,2006
G Raghu*,1 JA Lasky,2 U Costabel*,3 KK Brown*,4 V Cottin,5 RM du Bois*,6 M Thomeer,7 J Utz*,8 L McDermott9
1University of Washington Medical Center, Seattle, WA 2Tulane University Medical Center , New Orleans, LA 3Ruhrlandklinik Essen-Heidhausen, Essen, Germany 4National Jewish Center, Denver, CO 5Center for Orphan Lung Diseases, Lyon, France 6Royal Brompton Hospital, London, UK, 7Universitaire Ziekenhuizen KULeuven, Leuven, Belgium 8Mayo Clinic, Rochester, MN 9Wyeth Research, Collegeville, PA
Sponsor: Wyeth Research *Consultants/Advisors
Proof of Concept Study : Etanercept in IPF(data presented Raghu et al CHEST NOV,05 and ERS Sept,06)
● 48 week, double-blind, placebo-controlled, randomized, parallel, multi-center international study – 88 IPF patients enrolled
– 85 in efficacy population, 87 in safety population– Primary comparison between groups: Baseline versus 48
weeks, LOCF
Placebo 2x/week S/C
Etanercept 25 mg 2x/week S/CScreen
48 weeks4 weeks
Proof of Concept Study : Etanercept in IPF(data presented at CHEST NOV,05 and ERS Sep.06)
Conclusions● Efficacy
– Primary and Secondary Endpoints not met– Trend in favor of etanercept for
– Multiple physiologic endpoints – Functional measures (6MWD, QoL)
– Post Hoc Analyses– Trend toward improved progression-free
survival– Highest treatment differences for tertile of
patients with entry FVC < 57%● Safety
– No significant difference in the overall incidence of adverse event, serious adverse events or infections between treatment groups
BUILD 1*
● A double-blind randomized placebo controlled multicenter study to assess the efficacy, tolerability, and safety of bosentan in patients with idiopathic pulmonary fibrosis (IPF)
* Sponsor : Actelion
BUILD 1 : Bosentan did not improve 6MWD up to 12 months (Primary Endpoint) (data presented at ATS* and
ERS meeting 5/06 and 9/06) : King*,Behr,Brown,Dubois** and Raghu)
All treated patients Placebon = 83
Bosentann = 71
Baseline (m)Mean (SD)Median
372 (74)387
375 (92)397
Month 12* (m)Mean (SD)Median
338 (162)369
323 (164)390
Change from baseline (m)Mean (SD)Median
-34 (127)-9
-52 (121)-23
Treatment effectMean (SE)Medianp-value (Mann-Whitney U-test)
-18 (20)-170.226
*Or earlier if premature discontinuation
BUILD 1 Predefined Population: In biopsy proven IPF, Bosentan delayed time to disease progression
or death(data presented at ATS*/ERS** meetings, 5 and 9/06:
King*,Behr,Brown,Dubois** and Raghu )
p=0.009
1009080706050403020100
0
Patients at risk
Placebo
Bosentan
Patients without event (%)
3 6 9 12 15Months treatment
50 47 42 36 24 0 Placebo49 47 42 41 22 0 Bosentan
BUILD 1: Summary and Conclusions data presented at ATS* and ERS** meetings 5 and 9/06 :
(King*,Behr,Brown,Dubois** and Raghu )
– Bosentan did not improve the primary endpoint of 6MWD
– Bosentan showed a trend to delayed time to disease progression or death
– In the predefined population with biopsy proven IPF, treatment effect was more pronounced
– Bosentan was well tolerated, with no unexpected adverse events
– These promising results will be investigated in a larger study (BUILD 3)
BUILD 1 : Dyspnea & QoL Conclusions of Results(Raghu et al,ERS Sep.06)
● QoL in IPF patients is severely compromised at baseline● Treatment with bosentan resulted in significant QoL
improvements at month 6; favorable trend observed at month 12
● Bosentan improved the overall well-being of IPF patients, especially in the biopsy-proven IPF subpopulation
● These results concur with the observed delay in time to death or disease progression in the bosentan group1
● Results will be further investigated in the long-term morbidity/mortality BUILD 3 study
1du Bois RM, et al. Bosentan in IPF patients, BUILD 1 study [poster]. Presented at ERS; Munich, Germany; 4 September 2006.
Idiopathic Pulmonary Fibrosis:Anticoagulant Therapy*
● Prospective randomized study in Japan● 56 IPF patients● Randomization:
– Prednisolone alone or– Prednisolone plus oral warfarin in the
outpatient setting and low molecular weight heparin in hospitalized patients with progressive respiratory failure
● Overall survival and hospitalization-free periods were assessed
* Kubo et al. Chest 2005; 128:1475-82
Idiopathic Pulmonary Fibrosis:Anticoagulant Therapy*
* Kubo et al. Chest 2005; 128:1475-82
P=0.049
P=0.3
● Poorly design study● Decision/Need for hospitalisation arbitrary ● All hospitalisations may not have had true acute
exacerbations .● Differential drop outs
Idiopathic Pulmonary Fibrosis:Anticoagulant Therapy*
Limitations
* Kubo et al. Chest 2005; 128:1475-82
IPF: Treatment with γ-Interferon
Does it work ?
IPF: Treatment with γ-Interferon
Raghu et al, NEJM , 2004; 350:125-133
IPF: Treatment with γ-Interferon
Raghu et al, NEJM , 2004; 350:125-133
INSPIRE
● Large multicenter trial designed to determine if IFN-γ provides survival benefits in patients with mild-to-moderate IPF
● Tested signals of survival benefits from post hoc analysis in an earlier phase III trial that failed to show benefits on primary composite outcome of progression-free survival(Raghu et al. N Engl J Med. 2004;350:125-133.)
Raghu G. Eur Respir J. 2006;28:463-465.
INSPIRE
● Study Terminated on March 05 2007*
● No survival benefits associated with Interferon-gamma
* InterMune press Release.
Insights from Recent Clinical Trials
Raghu G. Eur Respir J. 2006;28:463-465.
Idiopathic Pulmonary Fibrosis
Clinical Course
* Martinez et al. AIM 2005; 142:963-7
New Insights on Disease Progression From Recent Clinical Trials
● Rapid decline of respiratory status precedes death in otherwise stable patients
● Remarkable stability without treatment in many patients
● Importance of acute exacerbations● Very low mortality during 1-yr follow-up in
patients with well-established IPF● Trials with true placebo-arm may be possible
based on observed stability without treatment
Raghu G. Eur Respir J. 2006;28:463-465.
● No differences in chosen primary endpoints between treatment groups– β interferon (Raghu et al. data presented ATS 2000)– γ interferon (Raghu et al. NEJM 2004;InterMune press
release March 2007)– Pirfenidone (Azuma et al. AJRCCM 2005)– Etanercept (Raghu et al. Chest Meeting Nov 05 and
ERS meeting Sep 06)– Bosentan (King et al. ATS, May 23, 2006)
● N-acetylcysteine (NAC) added to prednisone and azathioprine preserved VC and DLCO better than prednisone + azathioprine (Demedts et al. NEJM 2005)
● Pirfenidone improves VC (Shionogi Press Release,Dec 06)
Idiopathic Pulmonary Fibrosis (Mild/Moderate):Treatment
1999 yr →1999 yr →
Ongoing MulticenterTrials in IPF(2007--)
Phase III ● Pirfenidone● Bosentan (BUILD III) ● Others (?)
Phase I ● Antibody against TGFβ● Others (?)
The Future of Therapy for Lung Fibrosis: Next Steps
Phase II ● Imitanib● Zilueton● Others(?)
Multicenter Clinical trials in IPF : (Aug 2007-- )Ongoing, just started and/or to begin
Phase III ● Pirfenidone (CAPACITY;PIPF-004 and-006)● (Bosentan (BUILD III)
● Prednisone-NAC-AZA(PANTHER,NIH)
● Others (?)
Phase I ● Antibody against TGFβ
● Others (?)
The Future of Therapy for Lung Fibrosis: Next Steps
Phase II ● Imitanib
● Zilueton(?)
● Phosphodiesterase inhibitor(STEP-IPF,NIH)
● Others(?)
Percieved* time line of concurrent/new IPF multicenter clinical studies: yr 2007----
2007 2008 2009 20112010 2012
BUILD III
CAPACITY :PIPF 004
OTHERS ------ ? ----------------------??
CAPACITY :PIPF 006
NIH PANTHER (anticipated to begin 8/07-- )
(pred-Aza-NAC)
NIH STEP-IPF (anticipated to begin 6-7/07-- )
NIH STEP-IPF (anticipated to begin 6-7/07-- )
IPF TreatmentIn pursuit of evidence based decisions*
● Many ongoing or planned phase I, II, and III trials now underway may need to amend/modify protocols based on the significance of the results of phase III trials that will become available during the initial or mid stages of ongoing studies.
*Raghu G. Eur Respir J. 2006;28:463-465.
Idiopathic Pulmonary Fibrosis (IPF): TreatmentChallenges for New, multicenter, clinical trials: Yr 1999→
Theoretic goals and realities (Yr 1999Theoretic goals and realities (Yr 1999 ))
Years
Specific new Rx
Functional impairment
Survival
•• ↓↓ rate of progressionrate of progression•• Improved functionImproved function•• Better quality of lifeBetter quality of life•• Prolong survivalProlong survival
Current Standard of Care?
● Prednisone + azathioprine has evolved as apparent “standard of care,” supplemented by other currently available prescription and over-the-counter medicines
● Subjective perceptions of patients and physicians based on signals from trials drive decisions, rather than grade A clinical trial evidence
Raghu G. Eur Respir J. 2006;28:463-465.
● Current standard of care: longstanding variability“Conventional” approaches
● Treatment deferred to worsening stages– Lone corticosteroids followed by adjunct
immunosuppression● “New guidelines” (Joint ATS/ERS Statement yr
2000) – Prednisone plus azathioprine
● Not based on scientific evidence
Idiopathic Pulmonary Fibrosis (Mild/Moderate)
Treatment
Standard of Care: Call to Action
● Clinical investigators must clarify current standard of care by providing new evidence
● Current chaotic and poor standard of care must be replaced
● Well-designed clinical trials will separate myth from facts and provide solid evidence to inform clinical decisions
Raghu G. Eur Respir J. 2006;28:463-465.
● clarify current standard of care
● improve standard of care
● Placebo control protocols for different stages of disease status(mild-moderate disease when diagnosed ; advanced stages)
● Revise existing international consensus statement for management of IPF
● Based on scientific evidence
Idiopathic Pulmonary Fibrosis Treatment : Immediate needs(absolute)
What Can We Do Now for Our Patients With IPF ?* - an evidence based approach
● No further harm/minimize iatrogenic problems● Interpret new data based on small nos. of patients with caution● Encourage patients to enroll in well-designed clinical trials● For those unwilling, unable, or ineligible to participate in trials,
provide option for conservative follow-up with “no specific medication” other than oxygen supplementation
● Provide the best supportive care possible based on clinical and physiological needs
● Monitor clinical course regularly; undertake appropriate diagnostic and therapeutic intervention for complications
● Consider lung transplantation in a timely manner for eligible patients
*Raghu G. Eur Respir J. 2006;28:463-465.
● Maximally suppress disease progression● Avoid potential complications● Identify deterioration● Lung transplantation in selected patients● Clinical trials
Idiopathic Pulmonary Fibrosis Therapy
Current Goals
Idiopathic Pulmonary Fibrosis: Treatment
● Very advanced endstages– Unable to walk a few steps because of
profound dyspnea and O2 desaturationdespite supplemental oxygen use
– Unable to perform PFTs (hold breath for DLco)
● Palliative, comfort measures
Idiopathic Pulmonary fibrosis Treatment options*
● No specific treatment other than supportive care
● Upfront Clinical trials
● Clinical trials at deterioration
● Lung transplantation at the earliest decline
● Prompt diagnostic and treatment interventions for complications
● Preventive measures : avoid exposures to fibrogenicfactors (environmental, antireflux)
● Prednisone plus azathioprine plus NAC?* personal approach
Idiopathic Pulmonary FibrosisTreatment: Suggested Approach*
IPF - Established Dx (Clinical, UIP)
? Ongoing clinical trials for initial Rx
Discuss prognosis, treatment options (introduce lung Tx)Baseline PFTs , HRCT, CBC, Chemistry, ABG, O2 sat walking,(echocardiogram?)
Yes No
Encourage patientsto participate
Oral Prednisone + azathioprine (2-3 mg/kg/d,not > 200 mg/day)40 mg/day x 15 d
20 mg/day x 3 mo
* Personal
(+/-NAC 600 mg tid)
Oral prednisone + azathioprine (+/-NAC)
3 month, 6 month f/u visits with PFTs, O2 sat during walk
6 months assess for:
Worse Stable Improve
Continue Rx
Blood test 15 d x 2, monthly x 3
Decrease prednisone 10-20 mg/d
* Personal
Idiopathic Pulmonary FibrosisTreatment: Suggested Approach*
Worse (3-6 months after initial Rx)
LungTx
? Superimposed problems Secondary to IPF
Appropriate Dx/Rx Discuss options
Clinicaltrials
Rx based onanecdotal experience
and/or new data
* Personal
• Follow-up 3 monthly with FVC, DLCO, SpO2 during walk, blood tests• 6-12 month PFTs:
•Improvement in FVC, DLCO, (predicts survival)•Deterioration (dismal prognosis, comfort care)•Stable
• 12 month echocardiogram• HRCT/CT 12 months, yearly (earlier if new, superimposed nodule/mass)
Monitoring
Idiopathic Pulmonary FibrosisTreatment: Suggested Approach*