TY - JOUR
T1 - Effect of Antifibrotic Therapy on Survival in Patients With Idiopathic Pulmonary Fibrosis
AU - IPF-PRO Registry investigators
AU - de Andrade, Joao A.
AU - Neely, Megan L.
AU - Hellkamp, Anne S.
AU - Culver, Daniel A.
AU - Kim, Hyun J.
AU - Liesching, Timothy
AU - Lobo, Leonard J.
AU - Ramaswamy, Murali
AU - Safdar, Zeenat
AU - Bender, Shaun
AU - Conoscenti, Craig S.
AU - Leonard, Thomas B.
AU - Palmer, Scott M.
AU - Snyder, Laurie D.
N1 - Funding Information:
The Idiopathic Pulmonary Fibrosis Prospective Outcomes/Interstitial Lung Disease ProspectiveOutcomes Registry (IPF-PRO/ILD-PRO) Registry is funded by Boehringer Ingelheim Pharmaceuticals, Inc and coordinated by the Duke Clinical Research Institute. Writing support was provided by Julie Fleming and Wendy Morris of Fleishman-Hillard, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc.
Funding Information:
The Idiopathic Pulmonary Fibrosis Prospective Outcomes/Interstitial Lung Disease ProspectiveOutcomes Registry (IPF-PRO/ILD-PRO) Registry is funded by Boehringer Ingelheim Pharmaceuticals, Inc and coordinated by the Duke Clinical Research Institute. Writing support was provided by Julie Fleming and Wendy Morris of Fleishman-Hillard, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. M.D. de Andrade, Ph.D. Neely, M.S. Hellkamp, M.D. Conoscenti, M.D. Leonard, M.D. Palmer, and M.D. Snyder were involved in the design of the study. M.D. de Andrade, M.D. Culver, M.D. Kim, M.D. Liesching, M.D. J Lobo, M.D. Ramaswamy, and M.D. Safdar were involved in data acquisition. Ph.D. Neely and M.S. Hellkamp were involved in data analysis. All authors were involved in the interpretation of the data and in the writing and critical review of the manuscript and have approved the final version. The authors thank the principal investigators and enrolling centers in the IPF-PRO Registry: Albert Baker, Lynchburg Pulmonary Associates, Lynchburg, VA; Scott Beegle, Albany Medical Center, Albany, NY; John A. Belperio, University of California Los Angeles, Los Angeles, CA; Rany Condos, NYU Medical Center, New York, NY; Francis Cordova, Temple University, Philadelphia, PA; Daniel A. Culver, Cleveland Clinic, Cleveland, OH; Daniel Dilling, Loyola University Health System, Maywood, IL; John Fitzgerald (formerly Leann Silhan), UT Southwestern Medical Center, Dallas, TX; Kevin R. Flaherty, University of Michigan, Ann Arbor, MI; Kevin Gibson, University of Pittsburgh, Pittsburgh, PA; Mridu Gulati, Yale School of Medicine, New Haven, CT; Kalpalatha Guntupalli, Baylor College of Medicine, Houston, TX; Nishant Gupta, University of Cincinnati Medical Center, Cincinnati, OH; Amy Hajari Case, Piedmont Healthcare, Atlanta, GA; David Hotchkin, The Oregon Clinic, Portland, OR; Tristan J. Huie, National Jewish Health, Denver, CO; Robert J. Kaner, Weill Cornell Medical College, New York, NY; Hyun J. Kim, University of Minnesota, Minneapolis, MN; Lisa H. Lancaster (formerly Mark Steele), Vanderbilt University Medical Center, Nashville, TN; Joseph A. Lasky, Tulane University, New Orleans, LA; Doug Lee, Wilmington Health and PMG Research, Wilmington, NC; Timothy Liesching, Lahey Clinic, Burlington, MA; Randolph Lipchik, Froedtert & The Medical College of Wisconsin Community Physicians, Milwaukee, WI; Jason Lobo, UNC Chapel Hill, Chapel Hill, NC; Tracy R. Luckhardt (formerly Joao A. de Andrade), University of Alabama at Birmingham, Birmingham, AL; Yolanda Mageto (formerly Howard Huang), Baylor University Medical Center at Dallas, Dallas, TX; Marta Kokoszynska (formerly Yolanda Mageto, Prema Menon), Vermont Lung Center, Colchester, VT; Lake Morrison, Duke University Medical Center, Durham, NC; Andrew Namen, Wake Forest University, Winston Salem, NC; Justin M. Oldham, University of California, Davis, Sacramento, CA; Tessy Paul, University of Virginia, Charlottesville, VA; David Zhang (formerly Anna Podolanczuk, David Lederer, Nina M. Patel), Columbia University Medical Center/NewYork-Presbyterian Hospital, New York, NY; Mary Porteous (formerly Maryl Kreider), University of Pennsylvania, Philadelphia, PA; Rishi Raj (formerly Paul Mohabir), Stanford University, Stanford, CA; Murali Ramaswamy, PulmonIx LLC, Greensboro, NC; Tonya Russell, Washington University, St. Louis, MO; Paul Sachs, Pulmonary Associates of Stamford, Stamford, CT; Zeenat Safdar, Houston Methodist Lung Center, Houston, TX; Shirin Shafazand (formerly Marilyn Glassberg), University of Miami, Miami, FL; Ather Siddiqi (formerly Wael Asi), Renovatio Clinical, The Woodlands, TX; Reginald Fowler (formerly Barry Sigal), Salem Chest and Southeastern Clinical Research Center, Winston Salem, NC; Mary E. Strek (formerly Imre Noth), University of Chicago, Chicago, IL; Hiram Rivas-Perez (formerly Jesse Roman, Sally Suliman), University of Louisville, Louisville, KY; Jeremy Tabak, South Miami Hospital, South Miami, FL; Rajat Walia, St. Joseph's Hospital, Phoenix, AZ; and Timothy P.M. Whelan, Medical University of South Carolina, Charleston, SC, USA. The data sets analyzed during the present study are not publicly available but are available from the corresponding author on reasonable request.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/4
Y1 - 2023/4
N2 - Purpose: Real-world studies have reported reduced mortality in patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotic therapy; however, the initiation or discontinuation of therapy during these studies may have introduced bias. This study investigated the effect of antifibrotic therapy on mortality and other outcomes in patients with IPF using causal inference methodology. Methods: Data from a multicenter US registry of patients with IPF were used to assess the effect of antifibrotic therapy (nintedanib or pirfenidone) on death, death or lung transplant, respiratory-related hospitalization, and acute worsening of IPF (defined as any health care encounter deemed due to acute worsening of IPF). This study used the Gran method, which accounts for differences in patient characteristics and for treatment initiations and discontinuations during follow-up. The analysis cohort was limited to patients who started antifibrotic therapy on or after the day of enrollment or had never taken it. Findings: Among the 499 patients analyzed, 352 (70.5%) received antifibrotic therapy. Estimated event rates of death at 1 year were 6.6% (95% CI, 6.1–7.1) for treated patients and 10.2% (95% CI, 9.5–10.9) for control patients. There was a numerical reduction in the risk of death (hazard ratio [HR], 0.53; 95% CI, 0.28–1.03; P = 0.060) but numerical increases in risks of respiratory-related hospitalization (HR, 1.88; 95% CI, 0.90–3.92; P = 0.091) and acute worsening of IPF (HR, 1.71; 95% CI, 0.36–8.09; P = 0.496) in treated versus control patients. Implications: Analyses based on causal inference methodology suggest that patients with IPF who receive antifibrotic therapy have improved survival.
AB - Purpose: Real-world studies have reported reduced mortality in patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotic therapy; however, the initiation or discontinuation of therapy during these studies may have introduced bias. This study investigated the effect of antifibrotic therapy on mortality and other outcomes in patients with IPF using causal inference methodology. Methods: Data from a multicenter US registry of patients with IPF were used to assess the effect of antifibrotic therapy (nintedanib or pirfenidone) on death, death or lung transplant, respiratory-related hospitalization, and acute worsening of IPF (defined as any health care encounter deemed due to acute worsening of IPF). This study used the Gran method, which accounts for differences in patient characteristics and for treatment initiations and discontinuations during follow-up. The analysis cohort was limited to patients who started antifibrotic therapy on or after the day of enrollment or had never taken it. Findings: Among the 499 patients analyzed, 352 (70.5%) received antifibrotic therapy. Estimated event rates of death at 1 year were 6.6% (95% CI, 6.1–7.1) for treated patients and 10.2% (95% CI, 9.5–10.9) for control patients. There was a numerical reduction in the risk of death (hazard ratio [HR], 0.53; 95% CI, 0.28–1.03; P = 0.060) but numerical increases in risks of respiratory-related hospitalization (HR, 1.88; 95% CI, 0.90–3.92; P = 0.091) and acute worsening of IPF (HR, 1.71; 95% CI, 0.36–8.09; P = 0.496) in treated versus control patients. Implications: Analyses based on causal inference methodology suggest that patients with IPF who receive antifibrotic therapy have improved survival.
KW - Disease progression
KW - Idiopathic pulmonary fibrosis
KW - Interstitial fibrosis
KW - Mortality
UR - http://www.scopus.com/inward/record.url?scp=85151341315&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85151341315&partnerID=8YFLogxK
U2 - 10.1016/j.clinthera.2023.03.003
DO - 10.1016/j.clinthera.2023.03.003
M3 - Article
C2 - 36997445
AN - SCOPUS:85151341315
VL - 45
SP - 306
EP - 315
JO - Clinical Therapeutics
JF - Clinical Therapeutics
SN - 0149-2918
IS - 4
ER -