New Therapies and Trials in IPF
|
|
- Terence Stokes
- 6 years ago
- Views:
Transcription
1 Conflict of interest disclosure I have the following real or perceived conflicts of interest that relate to this presentation: New Therapies and Trials in IPF Talmadge E. King, Jr., M.D. Julius R. Krevans Distinguished Professorship in Internal Medicine Chair, Department of Medicine University of California San Francisco (UCSF) San Francisco, CA InterMune (Drug Study Steering committees) F. Hoffmann-La Roche/Genentech (Drug Study Steering committees) Actelion(Drug Study Steering Committees) ImmuneWorks(Scientific Advisory Committee) GlaxoSmithKline (Consultant) Boehringer Ingelheim (Consultant) Daiichi Sankyo (Consultant) Tracon(Consultant) NIH IPFnet(Principal investigator) UpToDate (Editor, Author) Talmadge E. King, Jr., MD Professor & Chair UCSF Department of Medicine Diffuse Parenchymal Lung Diseases or Interstitial Lung Diseases (ILD) Heterogeneous group of noninfectious, nonmalignant processes of the lower respiratory tract (interstitial pneumonias) that commonly result Symptoms: dyspnea and cough Signs: crackles on chest exam; (clubbing) PFTs: restrictive ventilatory impairment Chest imaging: diffuse interstitial opacities Lung biopsy: granulomatous or interstitial inflammation and fibrosis Outcome: often progressive and often fatal Diffuse Parenchymal Lung Diseases Chronic Fibrosing Idiopathic pulmonary fibrosis Idiopathic nonspecific interstitial pneumonia Idiopathic interstitial pneumonia (IIPs) Non-familial (>8%) Familial (2-2%) 2%) Acute/Subacute Fibrosing Cryptogenic organizing pneumonia Acute interstitial pneumonia Smoking-related Respiratory bronchiolitis ILD Desquamative interstitial pneumonia 1
2 Approach to the Diagnosis of ILD: It Often Takes A Village! Primary Care Pulmonologists Clinical History Physical Laboratory PFTs Rheumatologists Radiology Chest X-ray HRCT Radiologists Pathologists Pathology Surgical lung biopsy Multidimensional and multidisciplinary Idiopathic Pulmonary Fibrosis 211 Joint ATS/ERS/JRS/ALAT Statement Am J Respir Crit Care Med 183: Specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring in adults (55 75 years), Associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP). ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 22;165: Incidence and prevalence of IPF increases markedly with age Per Hundred Thousand Incidence Male Female Per Hundred Thousand Prevalence Male Female Clinical course of IPF/UIP is variable and may be difficult to predict Estimated 31, New Patients per Year in the United States Estimated 83, Current Patients in the United States WeyckerD, et al. Prevalence, Incidence, and Economic Costs of Idiopathic Pulmonary Fibrosis. Paper presented at: CHEST 22 San Diego, CA. 2
3 Heterogeneous Natural History Pattern In Patients With IPF IPF is notan inflammatory disorder It is a fibroproliferativedisorder preceded by epithelial activation. King, Pardo, Selman. Lancet 211; 378: Selman, M. King TE, Jr, PardoA. Idiopathic Pulmonary Fibrosis: Progress in Understanding Its Pathogenesis and Implications for Therapy. Ann Intern Med 21; 134;: Primary Sites of Ongoing Injury and Repair Are the Fibroblast Foci Age & Pathogenesis Multiple microfoci of epithelial injury Type 2 pneumocyte proliferation and activation IPF may represent a primary failure of the alveolar epithelium, due in part to age-related changes in cellular function. Focal fibroblast proliferation Selman, M. King TE, Jr, PardoA. Idiopathic Pulmonary Fibrosis: Progress in Understanding Its Pathogenesis and Implications for Therapy. Ann Intern Med 21; 134;:
4 October 15, 214 Why has it taken so long to get here? The FDA granted Esbriet(pirfenidone) and Ofev(nintedanib) fast track, priority review, orphan product, and breakthrough designations. To date Current animal models are NOTuseful in the development of novel therapies for IPF because animal models do NOT produce a fibrotic injury that looks or acts in any way like IPF/UIP! Need to rely more on translational rather than basic science. IPFnetis a network of ~26 medical centers across the U.S.A. dedicated to the study of IPF PANTHER Trials 4
5 Why Did We Use Corticosteroids to Treat IPF? We confused ourselves about the value of prednisone (with or without cytotoxic agents)! Rationale: treat inflammation, slow fibroblastic proliferation and prevent irreversible fibrosis Some patients experience a precipitous decline when steroids were stopped, so, they appeared to be working No other therapy available If you remember I did mention possible side effects. ILD: Responsiveness to Treatment OP Bronchiolitis UIP NSIP RB-ILD Eos Pn DIP DAD DAH Familial IPF AIP We over valued underpowered, poorly designed studies of therapies. LIP Vasc LAM PAP Amyloid 5
6 Cyclophosphamide Appears to Improve Survival in IPF 1 Prednisolone + Cyclophosphamide (n=21) 8 % Still alive 6 4 Prednisolone (n=22) p = N.S. 2 Many patients, however, failed to respond to either treatment Y e a r s Johnson et al. Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis. Thorax 1989;44: Chest. 24; 125: We ignored the widely recognized adverse events associated with common therapies. 6
7 We could not agree on disease definition. Am J RespirCritCare Med Vol161. pp , 2 NO GLOBAL INVOLVEMENT UNTIL ~2: More precise diagnosis Pharmaceutical company interest Patient encouragement and advocacy Slide courtesy of Luca Richeldi What have we tried King IFN-γ Imatinib STEP Sildenafil Anti-CCL2 Anti-TGFβ Demedts NAC PANTHER NAC Treatment Trials Johnson Cyclophosphamide Winterbauer Azathioprine Raghu Azathioprine Douglas Colchicine Raghu Pirfenidone Ziesche IFN-γ Raghu IFN-γ Azuma Pirfenidone TOMORROW Nintedanib Shionogi Pirfenidone King Bosentan CAPACITY 1/2 Pirfenidone Infliximab BUILD-3 Bosentan INPULSIS 1 & 2 Nintedanib ASCEND Pirfenidone Raghu Etanercept Ambrisentan Anti-inflammatory Immunosuppression Immunomodulation Anti-oxidant Kubo Warfarin Anti-fibrotic ACE Warfarin Anti-proliferative 7
8 There is no cure for IPF/UIP. Can we slow the progression or improve survival of IPF/UIP? IFIGENIA Trial PANTHER trial NAC Trial INPLUSIS-1 and INPLUSIS-2 ASCEND Trial IFIGENIA NAC + azathioprine + steroids 8
9 IFIGENIA Trial NEJM 25; 353: Baseline Endpoint 6m Endpoint 12m Mortality N Engl J Med 25;353: VC (% Predicted) NAC Placebo 9% 11% Pred/Aza/NAC (n=) Pred/Aza/Placebo (n=) IMPLICATIONS FOR PATIENT CARE NAC Treatment for IPF Addition of NAC to low-dose prednisone and azathioprine may help to preserve pulmonary function in patients with IPF. However, a drop-out rate of 3% (including deaths) raised concerns regarding the clinical relevance and robustness of the treatment effect. PANTHER NAC + azathioprine + steroids 9
10 Time Until Disease Progression or Death (Decrease in Forced Vital Capacity of 1%) Kaplan Meier Curve HR 1.46 (95% CI:.7 3.5) P =.3 N Engl J Med 212; 366: The Idiopathic Pulmonary Fibrosis Clinical Research Network. N Engl J Med 212;366: Time Until Hospitalization or Death Time until Death Kaplan Meier Curve HR: 3.74 (95% CI: ) p<.1 Kaplan Meier Curve HR 9.26 (95% CI ) P =.1 The Idiopathic Pulmonary Fibrosis Clinical Research Network. N Engl J Med 212;366: The Idiopathic Pulmonary Fibrosis Clinical Research Network. N Engl J Med 212;366:
11 Triple therapy had higher incidence of adverse events than placebo Percentage P-values <.5 Placebo Pred/Aza/NAC IMPLICATIONS FOR PATIENT CARE Treatment of IPF Compelling evidence against the use of the combination of azathioprine, prednisone, and NAC for patients with IPF who have mild-to-moderate impairment in pulmonary function. Death rates in clinical trials are below historical expectation. Raghu G, et al. N Engl J Med. 212;366: Demonstrates Mild to Moderate IPF Patients Have a Low Mortality Rate 1 95 Death Rate in IPF Has Declined? 1 8 IPF patients in placebo groups from INSPIRE and CAPACITY Trials (n=622) NSIP Percent Survival 9 % Alive UIP Weeks Placebo patients from INSPIRE and CAPACITY Trials (n=622) Years Daniil ZD et al. Am J Respir Crit Care Med. 1999;16:
12 PANTHER N-acetylcysteine(NAC) N Engl J Med 214; 37: NAC Does Not Reduce FVC Decline Acetylcysteine offered no significant benefit with respect to the preservation of FVC in patients with IPF with mild-to - moderate impairment in lung function. Martinez FJ, et al. N Engl J Med. 214;37(22): N Engl J Med 214; 37: N Engl J Med 214; 37:
13 NAC Trial: Conclusions As compared with placebo, acetylcysteine offered no significant benefit with respect to the preservation of FVC in patients with idiopathic pulmonary fibrosis with mild-to - moderate impairment in lung function. INPULSIS Nintedanib Possible Mechanisms of Nintedanib Action N Engl J Med. 214;37: Nintedanib Triple kinase inhibitor Phosphatase activator Antiangiogenic, antitumor activity VEGF PDGF FGF SHP-1 Pleiotropic Effects Hilberg F, et al. Cancer Res. 28;68(12): Tai WT, et al. J Hepatol. 214;61(1):
14 Annual rate of change in FVC was significantly lower in the nintedanib Nintedanib Reduces Loss of FVC 52% Relative Reduction 45% Relative Reduction INPULSIS 1 INPULSIS 2 INPULSIS 1 INPULSIS 2 A significantly greater proportion of patients in nintedanibgroup had noabsolute decline in the % predicted FVC 5% points Time to 1 st acute exacerbation No INPULSIS 1 Yes INPULSIS 2 14
15 Common Nintedanib Adverse Events Event Nintedanib (n = 39) INPULSIS-1 Placebo (n = 24) Nintedanib (n = 329) INPULSIS-2 Placebo (n = 219) Any (%) Diarrhea (%) Nausea(%) Richeldi L, et al. N Engl J Med. 214;37(22): INPULSIS trials: CONCLUSION Nintedanibreduced the decline in FVC, which is consistent with a slowing of disease progression There was significant differences in favor of nintedanibfor the time to first acute exacerbation and the change from baseline in the total SGRQ score in INPULSIS-2 but not INPULSIS-1. Nintedanib was frequently associated with diarrhea, which lead to discontinuation of the study medication in less than 5% of patients. ASCEND Pirfenidone Richeldi L, et al. N Engl J Med. 214;37(22):
16 Possible Mechanisms of Pirfenidone Action Pirfenidone TNF-α IL-6 TGF-β IL-6 MMPs Collagenases ROIs Antifibrotic Molecular target unclear Collagen Active in several animal models of fibrosis (lung, liver, kidney) 61 Hilberg O, et al. Clin Respir J. 212;6: Primary Efficacy Analysis: Treatment with pirfenidone resulted in a significant between-group difference in the rank ANCOVA analysis (P<.1) Proportion of Patients with 1% FVC Decline or Death (%) Pirfenidone (N=278) Placebo (N=277) Week Absolute Difference 2.5% 7.9% 12.3% 15.3% Relative Difference 54.% 58.% 57.8% 47.9% Rank ANCOVA p-value <.1 <.1.2 <.1 48% Relative Reduction Supportive Analysis of the Primary Endpoint: Treatment group difference of 193 ml at Week 52, a 45% relative reduction in the mean change in FVC Mean change in FVC (ml) Pirfenidone (N=278) 235 ml Placebo (N=277) Week Absolute difference, ml Relative difference 62.5% 54.9% 43.9% 45.1% Rank ANCOVA P-value <.1 <.1.2 < ml King TE, et al. N Engl J Med. 214;37(22):
17 ASCEND Study Supportive Analysis: Annual rate of FVC decline at week 52 favored Pirfenidone (Linear Slope Analysis) Annual Rate of FVC Change (ml/yr) Pirfenidone (N=278) Placebo (N=277) Absolute Difference, 116 ml/yr Relative reduction: 41.5% P<.1* * Linear slope analysis: Mixed model with linear time effect adjusted for age, height, and sex 65 More Pirfenidone Patients Maintain Walk Distance or Survive Proportion of Patients with 5 m Decline or Death (%) Pirfenidone (N=278) Week Absolute Difference 3.7% 1.9% 1.9% 9.8% Relative Difference 24.1% 39.7% 31.8% 27.5% Rank ANCOVA p-value* * Tested for multiple comparisons using the Hochberg procedure Progression-free Survival*: Pirfenidone reduced the risk of disease progression or death by 43% Patients (%) HR.57 (95% CI,.43.77) P<.1 Pirfenidone (N=278) Placebo (N=277) Patients at Risk: Week Pirfenidone Placebo * Time to death or disease progression (confirmed 1% decline in FVC or confirmed 5 m decline in 6MWD) Log-rank test 67 ASCEND Adverse Events Adverse Event Pirfenidone (%) Placebo (%) (N = 278) (N = 277) Δ (%) Nausea Rash Dyspepsia Anorexia GERD Weight Loss Insomnia Dizziness Vomiting Dyspnea Cough IPF King TE, et al. N Engl J Med. 214;37(22):
18 ASCEND Study: Summary Treatment with pirfenidone for 52 weeks significantly reduced disease progression, as measured by Changes in % predicted FVC (p<.1) Changes in 6-minute walk distance (p=.36) Progression-free survival (p<.1) Treatment with pirfenidone reduced all-cause mortality and treatment emergent IPF-related mortality in pooled analyses at week 52. Pirfenidone was generally safe and well tolerated. ASCEND Study: Conclusions Pirfenidone, as compared with placebo, reduced disease progression in patients with IPF. Treatment was generally safe, had an acceptable side effectprofile and was associated with fewer deaths New Paradigm for Effective Management of IPF/UIP IPF Comorbidities GERD Combined Pulmonary Fibrosis and Emphysema (CPFE) Pulmonary arterial hypertension (PAH) Lung cancer Raghu G et al. Am J Respir Crit Care Med. 211;183:
19 Goals of effective IPF management Relieve symptoms Improve exercise tolerance Improve health status Prevent and treat complications Prevent and treat exacerbations Prevent disease progression Reduce mortality Cough, Depression, Sleep, Pulmonary rehab., GERD, Supplemental Oxygen New approaches needed?? Pirfenidone N-acetylcysteine(Fluimucil ) Nintedanib Sildenafil (advanced disease) Lung transplantation IPF Drugs in the Works Gilead: Simtuzumab(anti-LOXL2) Fibrogen: FGCL (anti-ctgf) Centocor: CNTO 888 (anti-ccl2) Novartis: QAX 576 (anti-il13) Promedior: PRM151 (Petraxin-2) Biogen: ST 1 (anti integrin αvβ6) MedImmune: Tralokinumab(anti-IL13) Sanofi: SAR (anti IL-4 and IL-13) These goals should be reached with a minimum of side effects from treatment THANK YOU FOR YOU ATTENTION. 19
New Horizons The Future of IPF and ILD
New Horizons The Future of IPF and ILD Talmadge E. King, Jr., M.D. Julius R. Krevans Distinguished Professorship in Internal Medicine Chair, Department of Medicine University of California San Francisco
More informationIPF AND OTHER FIBROSING LUNG DISEASE: WHAT DRUGS MIGHT WORK AND ON WHOM DO THEY W ORK?
IPF AND OTHER FIBROSING LUNG DISEASE: WHAT DRUGS MIGHT WORK AND ON WHOM DO THEY W ORK? KEVIN K. BROWN, MD PROFESSOR AND VICE CHAIRMAN, DEPARTMENT OF MEDICINE NATIONAL JEWISH HEALTH DENVER, CO Kevin K.
More informationDisclosures. Traditional Paradigm. Overview 4/17/2010. I have relationships with the following organizations and companies:
Disclosures Pharmacological Therapy for ILD What to Use and How to Use It Harold R Collard MD Interstitial Lung Disease Program University of California San Francisco (UCSF) I have relationships with the
More informationUpdate on Therapies for Idiopathic Pulmonary Fibrosis. Outline
Update on Therapies for Idiopathic Pulmonary Fibrosis Paul Wolters Associate Professor University of California, San Francisco Outline Classification of Interstitial lung disease Clinical classification
More informationTherapies for Idiopathic Pulmonary Fibrosis Pharmacologic, Non-Pharmacologic
Therapies for Idiopathic Pulmonary Fibrosis Pharmacologic, Non-Pharmacologic Amy Olson, MD, MSPH Associate Professor, Division of Pulmonary and Critical Care Medicine National Jewish Health, Denver, CO
More informationNintedanib and Pirfenidone: New Medications in the Management of Idiopathic Pulmonary Fibrosis
Nintedanib and Pirfenidone: New Medications in the Management of Idiopathic Pulmonary Fibrosis Brad Zimmermann, PharmD, MBA Pharmacy Grand Rounds May 02, 2017 Rochester, Minnesota 2017 MFMER slide-1 Objectives
More informationPresente e futuro della terapia della fibrosi polmonare idiopatica
Presente e futuro della terapia della fibrosi polmonare idiopatica Antonella Caminati U.O. di Pneumologia e Terapia Semi Intensiva Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare Osp.
More informationConnective Tissue Disorder- Associated Interstitial Lung Disease (CTD-ILD) and Updates
Connective Tissue Disorder- Associated Interstitial Lung Disease (CTD-ILD) and Updates Maria Elena Vega, M.D Assistant Professor of Medicine Lewis Katz School of Medicine at Temple University Nothing to
More informationControversies in Clinical Trials. Pirfenidone for Idiopathic Pulmonary Fibrosis (IPF)
Controversies in Clinical Trials Pirfenidone for Idiopathic Pulmonary Fibrosis (IPF) Controversies to be highlighted by IPF Post-hoc analyses Story Primary end point selection Changing prespecified endpoints
More informationINTERSTITIAL LUNG DISEASES: FOCUS ON IDIOPATHIC PULMONARY FIBROSIS (IPF)
INTERSTITIAL LUNG DISEASES: FOCUS ON IDIOPATHIC PULMONARY FIBROSIS (IPF) Marilyn K. Glassberg Csete, M.D. Professor of Medicine, Surgery, and Pediatrics Director, Interstitial and Rare Lung Disease Program
More informationOverview of Idiopathic Pulmonary Fibrosis: Diagnosis and Therapy
Overview of Idiopathic Pulmonary Fibrosis: Diagnosis and Therapy Jeff Swigris, DO, MS Director, ILD Program National Jewish Health Disclosures Speaker - Boehringer Ingelheim and Genentech Objectives Describe
More informationChallenges in Pulmonary and Critical Care: 2018
Challenges in Pulmonary and Critical Care: 2018 Interstitial Lung Disease: Evolving Our Understanding of a Deadly Disease 1 Faculty Kevin Flaherty, MD, MS Professor in Pulmonary and Critical Care Medicine
More informationConflicts of Interest. Advisory Board: Boehringer-Ingleheim, Genentech/Roche DSMB: Bristol-Myers Squibb, Fibrogen Clinical Endpoint Committee; Merck
Conflicts of Interest Advisory Board: Boehringer-Ingleheim, Genentech/Roche DSMB: Bristol-Myers Squibb, Fibrogen Clinical Endpoint Committee; Merck The Idiopathic Interstitial Pneumonias Idiopathic pulmonary
More informationManagement of Idiopathic Pulmonary Fibrosis
Management of Idiopathic Pulmonary Fibrosis Robert Hallowell, M.D. December 22, 2015 Disclosures No financial disclosures What causes IPF? +? VEGF-R Airspace lining TNFa Fibrocytes PDGF Fibroblasts IL-1
More informationNAVIGATING the NEW ERA in IPF: Idiopathic Pulmonary Fibrosis
NAVIGATING the NEW ERA in IPF: Idiopathic Pulmonary Fibrosis Mark J Rumbak, MD Division Director Pulmonary, Critical Care and Sleep Medicine Morsani College of Medicine University of South Florida, Tampa
More informationWim Wuyts. Treatment of idiopathic interstitial pneumonias. March 12 th Interstitial lung diseases state of the art.
nterstitial ungdiseases euven Department of pneumology Unit for interstitial lung diseases University Hospitals Leuven March 12 th 2015 Interstitial lung diseases state of the art Treatment of idiopathic
More informationPerspectives ILD Diagnosis and Treatment in 5-10 years
Perspectives ILD Diagnosis and Treatment in 5-10 years Brett Ley, MD Department of Medicine The (Near) Future of ILD Diagnosis and Treatment 1. Combination therapy for Idiopathic Pulmonary Fibrosis 2.
More informationProgress in Idiopathic Pulmonary Fibrosis
Progress in Idiopathic Pulmonary Fibrosis David A. Lynch, MB Disclosures Progress in Idiopathic Pulmonary Fibrosis David A Lynch, MB Consultant: t Research support: Perceptive Imaging Boehringer Ingelheim
More informationPNEUMOLOGIA 2018 Milano, giugno 2018 INTERSTIZIOPATIE E MALATTIE RARE. Il futuro dell IPF: dove stiamo andando. Carlo Albera
PNEUMOLOGIA 2018 Milano, 14 16 giugno 2018 INTERSTIZIOPATIE E MALATTIE RARE Il futuro dell : dove stiamo andando Carlo Albera Università di Torino, Scuola di Medicina Dipartimento di Scienze Cliniche e
More informationPathologic Assessment of Interstitial Lung Disease
Pathologic Assessment of Interstitial Lung Disease Dry and itchy? It could be eczema or fungal infection. We don t need to worry, the drugs aren t that dangerous. Kirk D. Jones, MD UCSF Dept. of Pathology
More informationDiagnostic challenges in IPF
Medicine, Nursing and Health Sciences Diagnostic challenges in IPF Dr Ian Glaspole Central and Eastern Clinical School, Alfred Hospital and Monash University March 2015 Disclosures Consultancy fees from
More informationOFEV MEDIA BACKGROUNDER
OFEV MEDIA BACKGROUNDER 1 What is OFEV (nintedanib*)? 2 How does OFEV (nintedanib*) work? 3 Data overview 4 OFEV (nintedanib*) approval status 1 What is OFEV (nintedanib*)? OFEV (nintedanib*) is a small
More informationCurrent diagnostic recommendations for ILD: The multidisciplinary meeting TSANZSRS ASM
Medicine, Nursing and Health Sciences Current diagnostic recommendations for ILD: The multidisciplinary meeting Dr Ian Glaspole Central and Eastern Clinical School, Alfred Hospital and Monash University
More informationIdiopathic Pulmonary Fibrosis Treatable and Not Idiopathic
Idiopathic Pulmonary Fibrosis Treatable and Not Idiopathic Brett Ley, MD University of California San Francisco CTS 1/26/18 Disclosures Speaker s bureau honorarium from Genentech (makers of pirfenidone)
More informationDIFFERENCES IN FIBROPROLIFERATIVE HEALING IN EXOGENEOUS AND IDIOPATHIC ILDs. ARE THERE ANY?
NIHR Southampton Respiratory Biomedical Research Unit DIFFERENCES IN FIBROPROLIFERATIVE HEALING IN EXOGENEOUS AND IDIOPATHIC ILDs. ARE THERE ANY? Fibrosing Interstitial Lung Diseases CPFS/WASOG/AIPO/ERS
More informationInterstitial Lung Disease (ILD)
Interstitial Lung Disease (ILD) ILD comprises more than 130 distinct disorders Characterized by cellular proliferation, cellular infiltration, and/or fibrosis of the lung parenchyma not due to infection
More informationInterstitial Lung Disease ILD: Definition
Interstitial Lung Disease 2007 Paul F. Simonelli,, MD, PhD, FCCP Clinical Director Center for Interstitial Lung Disease Columbia University Medical Center 1. ILD is not one disorder ILD: Definition 2.
More informationOfficial ATS/ERS/JRS/ALAT Clinical Practice Guidelines: Treatment of Idiopathic Pulmonary Fibrosis
Official ATS/ERS/JRS/ALAT Clinical Practice Guidelines: Treatment of Idiopathic Pulmonary Fibrosis An Update of the 2011 Clinical Practice Guideline Online Supplement Ganesh Raghu, Bram Rochwerg, Yuan
More informationNINTEDANIB MEDIA BACKGROUNDER
NINTEDANIB MEDIA BACKGROUNDER 1. What is nintedanib? 2. How does nintedanib work? 3. Data overview 4. International treatment guidelines for IPF 1. What is nintedanib? Nintedanib (OFEV a ) is a small molecule
More information4/17/2010 C ini n ca c l a Ev E a v l a ua u t a ion o n of o ILD U dat a e t e i n I LDs
Update in ILDs Diagnosis 101: Clinical Evaluation April 17, 2010 Jay H. Ryu, MD Mayo Clinic, Rochester MN Clinical Evaluation of ILD Outline General aspects of ILDs Classification of ILDs Clinical evaluation
More informationTriple kinase inhibitor with phosphodiesterase-5 inhibitor for idiopathic pulmonary fibrosis
Editorial Triple kinase inhibitor with phosphodiesterase-5 inhibitor for idiopathic pulmonary fibrosis Tomoo Kishaba Department of Respiratory Medicine, Okinawa Chubu Hospital, Uruma City, Okinawa, Japan
More informationChallenges in the Diagnosis of Interstitial Lung Disease
Challenges in the Diagnosis of Interstitial Lung Disease Kirk D. Jones, MD UCSF Dept. of Pathology kirk.jones@ucsf.edu Overview New Classification of IIP Prior classification Modifications for new classification
More informationInternational consensus statement on idiopathic pulmonary fibrosis
Eur Respir J 2001; 17: 163 167 Printed in UK all rights reserved Copyright #ERS Journals Ltd 2001 European Respiratory Journal ISSN 0903-1936 PERSPECTIVE International consensus statement on idiopathic
More informationINHALED TREPROSTINIL IN PULMONARY HYPERTENSION DUE TO INTERSTITIAL LUNG DISEASE (PH-ILD)
THE INCREASE STUDY INHALED TREPROSTINIL IN PULMONARY HYPERTENSION DUE TO INTERSTITIAL LUNG DISEASE (PH-ILD) Peter Smith, PharmD Senior Director Product Development, United Therapeutics Corporation 2 SAFE
More informationGuidelines for Diagnosis and Treatment of IPF
Guidelines for Diagnosis and Treatment of IPF Katerina Antoniou, MD, PhD Lecturer in Thoracic Medicine ERS ILD Group Secretary Medical School, University of Crete Classification of Interstitial Lung Disease
More informationCTD-related Lung Disease
13 th Cambridge Chest Meeting King s College, Cambridge April 2015 Imaging of CTD-related Lung Disease Dr Sujal R Desai King s College Hospital, London Disclosure Statement No Disclosures / Conflicts of
More informationStrategies for Updated Treatment Options for IPF
Strategies for Updated Treatment Options for IPF Paul W. Noble, MD Vera and Paul Guerin Family Distinguished Chair in Pulmonary Medicine Professor and Chair Department of Medicine Director, Women's Guild
More informationIdiopathic pulmonary fibrosis
Pharmacologic Treatments for Idiopathic Pulmonary Fibrosis This chronic disease has historically lacked an effective treatment option, but the FDA recently approved two: pirfenidone and nintedanib. This
More informationNon-neoplastic Lung Disease II
Pathobasic Non-neoplastic Lung Disease II Spasenija Savic Prince Pathology Program Systematic approach to surgical lung biopsies with ILD Examples (chronic ILD): Idiopathic interstitial pneumonias: UIP,
More informationDisclosures. Fibrotic lung diseases: Basic Principles, Common Problems, and Reporting. Relevant financial relationships: None. Off-label usage: None
Fibrotic lung diseases: Basic Principles, Common Problems, and Reporting Brandon T. Larsen, MD, PhD Senior Associate Consultant Department of Laboratory Medicine and Pathology Mayo Clinic Arizona Arizona
More informationINTERSTITIAL LUNG DISEASE. Radhika Reddy MD Pulmonary/Critical Care Long Beach VA Medical Center January 5, 2018
INTERSTITIAL LUNG DISEASE Radhika Reddy MD Pulmonary/Critical Care Long Beach VA Medical Center January 5, 2018 Interstitial Lung Disease Interstitial Lung Disease Prevalence by Diagnosis: Idiopathic Interstitial
More informationExperience with the Compassionate Use Program of nintedanib for the treatment of Idiopathic Pulmonary Fibrosis in Argentina
ORIGINAL 131 RAMR 2017;2:131-135 ISSN 1852-236X Correspondence Gabriela Tabaj gabrielatabaj@gmail.com Received: 11.15.2016 Accepted: 02.03.2017 Experience with the Compassionate Use Program of nintedanib
More informationCase Presentations in ILD. Harold R. Collard, MD Department of Medicine University of California San Francisco
Case Presentations in ILD Harold R. Collard, MD Department of Medicine University of California San Francisco Outline Overview of diagnosis in ILD Definition/Classification High-resolution CT scan Multidisciplinary
More informationRegulatory Status FDA-approved indication: Ofev is a kinase inhibitor indicated for the treatment of idiopathic pulmonary fibrosis (IPF) (1).
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.45.05 Subject: Ofev Page: 1 of 5 Last Review Date: March 17, 2017 Ofev Description Ofev (nintedanib)
More informationLimitations of Corticosteroids and Cytotoxic Agents in Treating Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis Limitations of Corticosteroids and Cytotoxic Agents in Treating Idiopathic Pulmonary Fibrosis JMAJ 46(11): 475 482, 2003 Kingo CHIDA Associate Professor, Second Division,
More information9/12/18. Emerging Challenges in Primary Care: Navigating the Maze of Interstitial Lung Disease: Improving Outcomes through Early Diagnosis
Emerging Challenges in Primary Care: 2018 Navigating the Maze of Interstitial Lung Disease: Improving Outcomes through Early Diagnosis Faculty Kevin Flaherty, MD, MS Professor in Pulmonary and Critical
More informationCurrent Management of IPF and. Dr R Lakshmi Narasimhan Dept of Pulmonary Medicine
Current Management of IPF and fibrosing ILDs Dr R Lakshmi Narasimhan Dept of Pulmonary Medicine Introduction Idiopathic pulmonary fibrosis clinical course is variable and long term survival is poor Therapy
More informationDiffuse Interstitial Lung Diseases: Is There Really Anything New?
: Is There Really Anything New? Sujal R. Desai, MBBS, MD ESTI SPEAKER SUNDAY Society of Thoracic Radiology San Antonio, Texas March 2014 Diffuse Interstitial Lung Disease The State of Play DILDs Is There
More informationDisclosures. IPF Medications: Practical Experience. Prednisone, Azathioprine, N acyetylcysteine. Case 1. Brett Ley, MD, MAS Assistant Professor, UCSF
IPF Medications: Practical Experience Disclosures Received speakers bureau honorarium from Roche/Genentech (makers of pirfenidone). Brett Ley, MD, MAS Assistant Professor, UCSF 67 y/o man 1 year cough
More informationEvaluating New Treatment Options
Evaluating New Treatment Options Steven D. Nathan, MD Clinical Practice Guideline Changes 211 ATS/ERS/JRS/ALAT Recommendations Treatment of IPF combines nonpharmacologic and pharmacologic strategies, and
More informationERS 2016 Congress Highlights Interstitial Lung Disease (ILD)
ERS 216 Congress Highlights Interstitial Lung Disease (ILD) London, UK September 3 rd 7 th 216 The 26 th European Respiratory Society International Congress, (ERS) the largest respiratory meeting in the
More informationDiagnosing ILD. What is important in 2016? Chris Grainge
Diagnosing ILD What is important in 2016? Chris Grainge Senior Staff Specialist Respiratory Medicine John Hunter Hospital Conjoint A/Prof University of Newcastle Conflict of interest I have acted as a
More informationUntil approximately 40 yrs ago, clinical. Assessing the treatment effect from multiple trials in idiopathic pulmonary fibrosis REVIEW: IPF
Eur Respir Rev 2012; 21: 124, 147 151 DOI: 10.1183/09059180.00000912 CopyrightßERS 2012 REVIEW: IPF Assessing the treatment effect from multiple trials in idiopathic pulmonary fibrosis Luca Richeldi ABSTRACT:
More information5/9/2015. Multi-disciplinary Approach to Diffuse Lung Disease: The Imager s Perspective. No, I am not a pulmonologist! Radiology
Multi-disciplinary Approach to Diffuse Lung Disease: The Imager s Perspective No, I am not a pulmonologist! Radiology Pathology Clinical 1 Everyone needs a CT Confidence in diagnosis Definitive HRCT +
More informationDiagnosing Idiopathic Pulmonary Fibrosis on Evidence-Based Guidelines
Diagnosing Idiopathic Pulmonary Fibrosis on Evidence-Based Guidelines Rebecca Keith, MD Assistant Professor, Division of Pulmonary and Critical Care Medicine National Jewish Health, Denver, CO Objectives
More informationNONE OVERVIEW FINANCIAL DISCLOSURES UPDATE ON IDIOPATHIC PULMONARY FIBROSIS/IPF (UIP) FOR PATHOLOGISTS. IPF = Idiopathic UIP Radiologic UIP Path UIP
UPDATE ON IDIOPATHIC PULMONARY FIBROSIS/IPF () FOR PATHOLOGISTS Thomas V. Colby, M.D. Professor of Pathology (Emeritus) Mayo Clinic Arizona FINANCIAL DISCLOSURES NONE OVERVIEW IPF Radiologic Dx Pathologic
More informationIdiopathic pulmonary fibrosis (IPF) is a progressive. Changing the idiopathic pulmonary fibrosis treatment approach and improving patient outcomes
Eur Respir Rev 2012; 21: 124, 161 167 DOI: 10.1183/09059180.00001112 CopyrightßERS 2012 REVIEW: IPF Changing the idiopathic pulmonary fibrosis treatment approach and improving patient outcomes Vincent
More informationA case of a patient with IPF treated with nintedanib. Prof. Kreuter and Prof. Heussel
A case of a patient with IPF treated with nintedanib Prof. Kreuter and Prof. Heussel Case Overview This case describes the history of a patient with IPF who, at the time of diagnosis, had symptoms typical
More informationUsual Interstitial pneumonia and Nonspecific Interstitial Pneumonia. Nitra and the Gangs.
Usual Interstitial pneumonia and Nonspecific Interstitial Pneumonia Nitra and the Gangs. บทน ำและบทท ๓, ๑๐, ๑๒, ๑๓, ๑๔, ๑๕, ๑๗ Usual Interstitial Pneumonia (UIP) Most common & basic pathologic pattern
More informationRandomized Trial of Acetylcysteine in Idiopathic Pulmonary Fibrosis
original article Randomized Trial of in Idiopathic Pulmonary Fibrosis The Idiopathic Pulmonary Fibrosis Clinical Research Network* ABSTRACT Background has been suggested as a beneficial treatment for idiopathic
More informationChallenges in the Diagnosis of Interstitial Lung Disease
Challenges in the Diagnosis of Interstitial Lung Disease Kirk D. Jones, MD UCSF Dept. of Pathology kirk.jones@ucsf.edu Overview New Classification of IIP Prior classification Modifications for new classification
More informationSummary of eligibility criteria for the Phase 3 multinational studies
SUPPLEMENTAL MATERIAL Table 1 Summary of eligibility criteria for the Phase 3 multinational studies CAPACITY (Studies 004 and 006) ASCEND (Study 016) Age 40 to 80 years Confident IPF diagnosis within the
More informationA Review of Interstitial Lung Diseases. Paul J. Wolters, MD Associate Professor Department of Medicine University of California San Francisco
A Review of Interstitial Lung Diseases Paul J. Wolters, MD Associate Professor Department of Medicine University of California San Francisco Outline Overview of diagnosis in ILD Why it is important Definition/Classification
More informationManagement of Co morbidities in Idiopathic Pulmonary Fibrosis. Disclosures
Management of Co morbidities in Idiopathic Pulmonary Fibrosis Joyce S. Lee, MD MAS Director, Interstitial Lung Disease Clinic University of California, San Francisco Disclosures Intermune, advisory board
More informationNovel approaches to pulmonary fibrosis
Clinical Medicine 2014 Vol 14, No 6: s45 s49 CHEST MEDICINE Novel approaches to pulmonary fibrosis Authors: Gisli Jenkins A and Amanda Goodwin B ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a devastating
More informationOutline Definition of Terms: Lexicon. Traction Bronchiectasis
HRCT OF IDIOPATHIC INTERSTITIAL PNEUMONIAS Disclosures Genentech, Inc. Speakers Bureau Tadashi Allen, MD University of Minnesota Assistant Professor Diagnostic Radiology 10/29/2016 Outline Definition of
More informationUnpaid scientific collaborator & advisor with Veracyte, Inc.
Diagnosis and Classification of Idiopathic Interstitial Pneumonias: Role of Histopathology in the Golden Age of Consensus Jeffrey L. Myers, M.D. A. James French Professor of Diagnostic Pathology Vice Chair
More informationCigna Drug and Biologic Coverage Policy
Cigna Drug and Biologic Coverage Policy Subject Idiopathic Pulmonary Fibrosis Therapy Table of Contents Coverage Policy... 1 General Background... 4 Coding/Billing Information... 7 References... 7 Effective
More informationIdiopathic pulmonary fibrosis: recent advances on pharmacological therapy
Accepted Manuscript Idiopathic pulmonary fibrosis: recent advances on pharmacological therapy P. Spagnolo, T.M. Maher, L. Richeldi PII: S0163-7258(15)00091-1 DOI: doi: 10.1016/j.pharmthera.2015.04.005
More informationA Review of Interstitial Lung Diseases
Outline A Review of Interstitial Lung Diseases Paul J. Wolters, MD Associate Professor Department of Medicine University of California San Francisco Overview of diagnosis in ILD Why it is important Definition/Classification
More informationLiebow and Carrington's original classification of IIP
Liebow and Carrington's original classification of IIP-- 1969 Eric J. Stern MD University of Washington UIP Usual interstitial pneumonia DIP Desquamative interstitial pneumonia BIP Bronchiolitis obliterans
More informationKD : A Phase 2 Trial of KD025 to Assess Safety, Efficacy and Tolerability in Patients with Idiopathic Pulmonary Fibrosis (IPF)
-207: A Phase 2 Trial of to Assess Safety, Efficacy and Tolerability in Patients with Idiopathic Pulmonary Fibrosis (IPF) K. F. Gibson 1, F. Averill 2, T.E. Albertson 3, D. M. Baratz 4, S. Chaudhary 5,
More informationSummary: Key Learning Points, Clinical Strategies, and Future Directions
Summary: Key Learning Points, Clinical Strategies, and Future Directions Introduction Idiopathic pulmonary fibrosis (IPF), a peripheral lobular fibrosis of unknown cause, is a chronic, progressive lung
More informationPulmonary manifestations of CTDs Diagnosis, differential diagnosis and treatment
Prague, June 2014 Pulmonary manifestations of CTDs Diagnosis, differential diagnosis and treatment Katerina M. Antoniou, MD, PhD As. Professor in Thoracic Medicine ERS ILD Group Secretary Medical School,
More informationPatient with FVC>90% predicted. Demosthenes Bouros, Vasilios Tzilas University of Athens
Patient with FVC>90% predicted Demosthenes Bouros, Vasilios Tzilas University of Athens CASE OVERVIEW A 63-year-old, male patient with progressive exertional dyspnoea lasting for 2 years and dry cough
More information11/10/2014. Multi-disciplinary Approach to Diffuse Lung Disease: The Imager s Perspective. Radiology
Multi-disciplinary Approach to Diffuse Lung Disease: The Imager s Perspective Radiology Pathology Clinical 1 Role of HRCT Diagnosis Fibrosis vs. inflammation Next step in management Response to treatment
More informationPFF HEALTH CARE PROFESSIONAL WEBINAR SERIES. Welcome!
PFF HEALTH CARE PROFESSIONAL WEBINAR SERIES Welcome! AGENDA TOPICS Welcome & Introduction Dr. Gregory Cosgrove, MD Chief Medical Officer Pulmonary Fibrosis Foundation PFF Resources Dolly Kervitsky, RCP,
More informationDifferential diagnosis
Differential diagnosis Idiopathic pulmonary fibrosis (IPF) is part of a large family of idiopathic interstitial pneumonias (IIP), one of four subgroups of interstitial lung disease (ILD). Differential
More informationDiscipline MCP5777 In-depth Study of the Treatment of Interstitial Idiopathic Pulmonary Fibrosis. Duration Total
Discipline MCP5777 In-depth Study of the Treatment of Interstitial Idiopathic Pulmonary Fibrosis Subject Area: 5150 Created: 27/11/2014 Active since: 27/11/2014 Number of credits: 1 Hours: Theoretical
More informationNew Drug Evaluation: Pirfenidone capsules, oral
Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119
More informationChallenges in the classification of fibrotic ILD
Review SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES 2015; 32; Suppl. 1: 4-9 Mattioli 1885 Challenges in the classification of fibrotic ILD Elisabeth Bendstrup 1, Toby M. Maher 2, Effrosyni D. Manali
More informationNew approaches to the design of clinical trials in idiopathic pulmonary fibrosis
New approaches to the design of clinical trials in idiopathic pulmonary fibrosis Clin. Invest. (2013) 3(6), 531 544 Idiopathic pulmonary fibrosis (IPF) is one of the major challenges for respiratory medicine,
More informationFaculty. Luca Richeldi, MD, PhD (Chair) Professor of Respiratory Medicine Chair of Interstitial Lung Disease University of Southampton Southampton, UK
Faculty Luca Richeldi, MD, PhD (Chair) Professor of Respiratory Medicine Chair of Interstitial Lung Disease University of Southampton Southampton, UK Kevin K. Brown, MD Professor of Medicine, Vice Chair,
More informationDIAGNOSTIC NOTE TEMPLATE
DIAGNOSTIC NOTE TEMPLATE SOAP NOTE TEMPLATE WHEN CONSIDERING A DIAGNOSIS OF IDIOPATHIC PULMONARY FIBROSIS (IPF) CHIEF COMPLAINT HISTORY OF PRESENT ILLNESS Consider IPF as possible diagnosis if any of the
More informationTBLB is not recommended as the initial biopsy option in cases of suspected IPF and is unreliable in the diagnosis of rare lung disease (other than
TBLB is not recommended as the initial biopsy option in cases of suspected IPF and is unreliable in the diagnosis of rare lung disease (other than PAP) BAL is not required as a diagnostic tool in patients
More informationTimely Topics in Pulmonary Medicine
Disclosures Timely Topics in Pulmonary Medicine I have nothing to disclose! Lorriana Leard, MD Associate Professor of Clinical Medicine Chief of Clinical Operations UCSF Pulmonary, Critical Care, Allergy
More informationCADTH CDEC FINAL RECOMMENDATION
CADTH CDEC FINAL RECOMMENDATION NINTEDANIB (Ofev Boehringer Ingelheim Canada Ltd.) Indication: Idiopathic Pulmonary Fibrosis Recommendation: The CADTH Canadian Drug Expert Committee (CDEC) recommends that
More informationFinancial disclosure COMMON DIAGNOSES IN HRCT. High Res Chest HRCT. HRCT Pre test. I have no financial relationships to disclose. Anatomy Nomenclature
Financial disclosure I have no financial relationships to disclose. Douglas Johnson D.O. Cardiothoracic Imaging Gaston Radiology COMMON DIAGNOSES IN HRCT High Res Chest Anatomy Nomenclature HRCT Sampling
More informationLines and crackles. Making sense of ILD
Lines and crackles Making sense of ILD Case JM 65 year old male Gradual shortness of breath, going on over a year Some dry cough Ex-smoker, quit 10 years ago Crackles in the bases CXR presented Sent to
More informationMedical Policy An independent licensee of the Blue Cross Blue Shield Association
Idiopathic Pulmonary Fibrosis Page 1 of 10 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Idiopathic Pulmonary Fibrosis (Esbriet /pirfenidone, Ofev /nintedanib)
More informationCareful histopathological evaluation has shown the traditionally clinical diagnosis of
Demystifying Idiopathic Interstitial Pneumonia Harold R. Collard, MD; Talmadge E. King, Jr, MD REVIEW ARTICLE Careful histopathological evaluation has shown the traditionally clinical diagnosis of idiopathic
More informationEvidence-based treatment strategies in idiopathic pulmonary fibrosis
Eur Respir Rev 2013; 22: 128, 163 168 DOI: 10.1183/09059180.00001013 CopyrightßERS 2013 REVIEW Evidence-based treatment strategies in idiopathic pulmonary fibrosis Jürgen Behr ABSTRACT: Recently updated
More informationBUILD-3: A Randomized, Controlled Trial of Bosentan in
BUILD-3: A Randomized, Controlled Trial of Bosentan in Idiopathic Pulmonary Fibrosis Talmadge E. King, Jr., MD; Kevin K. Brown, MD; Ganesh Raghu, MD; Roland M. du Bois, MD; David Lynch, MD; Fernando Martinez,
More informationCase Presentation. Case Presentation (continued) PHYSICAL EXAMINATION. 60 year old college professor dyspnea with exertion dry cough, throat clearing
Primary Care Medicine: Concepts and Controversies Thursday, February 18, 21 Fiesta Americana Puerto Vallarta, Mexico Interstitial Lung Disease: A Clinician s Approach to Diagnosis and Management Talmadge
More informationRelative versus absolute change in forced vital capacity in idiopathic pulmonary fibrosis
Thorax Online First, published on March 22, 2012 as 10.1136/thoraxjnl-2011-201184 Interstitial lung disease < Additional materials are published online only. To view these files please visit the journal
More informationCurrent approaches to the diagnosis and treatment of idiopathic pulmonary fibrosis in Europe: the AIR survey
REVIEW IDIOPATHIC PULMONARY FIBROSIS Current approaches to the diagnosis and treatment of idiopathic pulmonary fibrosis in Europe: the AIR survey Vincent Cottin 1,2 Affiliations: 1 Hospices Civils de Lyon,
More informationDefinition, classification and epidemiology
Interstitial Lung Diseases Definition, classification and epidemiology Haluk Türktaş Professor of Pulmonary Medicine Gazi University Ankara Interstitial Lung Diseases Definition of ILD A diverse group
More informationInvestor Update. Services. Investor Relations team Send . Basel, 24 May Subscribe to Roche news
Investor Update Basel, 24 May 2017 New data at ATS add to the body of evidence for Roche s Esbriet (pirfenidone) in idiopathic pulmonary fibrosis (IPF) In new post hoc analyses of phase III data, Esbriet
More informationDM SEMINAR AUGUST 13, 2004
DM SEMINAR AUGUST 13, 2004 IDIOPATHIC INTERSTITIAL PNEUMONIAS - UPDATE Navneet Singh Department of Pulmonary Medicine HEADINGS INTRODUCTION CLASSIFICATION APPROACH TO PATIENT WITH IIP CLINICAL-RADIOLOGICAL-
More information