Steven D Nathan1, Ulrich Costabel2, Ian Glaspole3, Marilyn K Glassberg4, Lisa H Lancaster5, David J Lederer6, Carlos A Pereira7, Benjamin Trzaskoma8, Elizabeth A Morgenthien8, Susan L Limb8, Athol U Wells9. 1. Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, VA. Electronic address: steven.nathan@inova.org. 2. Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany. 3. Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC, Australia. 4. Department of Medicine, University of Miami Miller School of Medicine, Miami, FL. 5. Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN. 6. Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY. 7. Lung Disease Department, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil. 8. Genentech, Inc., South San Francisco, CA. 9. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, England.
Abstract
BACKGROUND: Declines in percent predicted FVC (% predicted FVC), declines in 6-min walk distance (6MWD), and respiratory hospitalizations are events associated with disease progression and mortality in idiopathic pulmonary fibrosis. The incidence of multiple events in the same patient over 12 months of pirfenidone treatment is unknown. METHODS: Patients who received pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624) in the ASCEND (study 016; NCT01366209) and CAPACITY (studies 004 and 006; NCT00287716 and NCT00287729) phase III trials were included in this post hoc analysis. Disease progression events were defined as relative decline in % predicted FVC ≥ 10%, absolute decline in 6MWD ≥ 50 m, respiratory hospitalization, or death from any cause. The incidence of disease progression events over 12 months was assessed. RESULTS: The most frequent disease progression events were declines in % predicted FVC (pirfenidone vs placebo; 202 vs 304 events) and declines in 6MWD (pirfenidone vs placebo; 265 vs 348 events). Fewer patients who received pirfenidone had more than one progression event compared with placebo (17.0% vs 30.1%; P < .0001). Death following one or more progression event occurred less frequently in the pirfenidone group than in the placebo group (2.1% vs 6.3%; P = .0002). CONCLUSIONS:Pirfenidone significantly reduced the incidence of multiple progression events and death after a progression event over 12 months of treatment compared with placebo. These findings suggest that continued treatment with pirfenidone confers a benefit despite the occurrence of any single disease progression event. TRIAL REGISTRY: ClinicalTrials.gov; Nos. NCT01366209, NCT00287716, and NCT00287729; URL: www.clinicaltrials.gov.
RCT Entities:
BACKGROUND:Declines in percent predicted FVC (% predicted FVC), declines in 6-min walk distance (6MWD), and respiratory hospitalizations are events associated with disease progression and mortality in idiopathic pulmonary fibrosis. The incidence of multiple events in the same patient over 12 months of pirfenidone treatment is unknown. METHODS:Patients who received pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624) in the ASCEND (study 016; NCT01366209) and CAPACITY (studies 004 and 006; NCT00287716 and NCT00287729) phase III trials were included in this post hoc analysis. Disease progression events were defined as relative decline in % predicted FVC ≥ 10%, absolute decline in 6MWD ≥ 50 m, respiratory hospitalization, or death from any cause. The incidence of disease progression events over 12 months was assessed. RESULTS: The most frequent disease progression events were declines in % predicted FVC (pirfenidone vs placebo; 202 vs 304 events) and declines in 6MWD (pirfenidone vs placebo; 265 vs 348 events). Fewer patients who received pirfenidone had more than one progression event compared with placebo (17.0% vs 30.1%; P < .0001). Death following one or more progression event occurred less frequently in the pirfenidone group than in the placebo group (2.1% vs 6.3%; P = .0002). CONCLUSIONS:Pirfenidone significantly reduced the incidence of multiple progression events and death after a progression event over 12 months of treatment compared with placebo. These findings suggest that continued treatment with pirfenidone confers a benefit despite the occurrence of any single disease progression event. TRIAL REGISTRY: ClinicalTrials.gov; Nos. NCT01366209, NCT00287716, and NCT00287729; URL: www.clinicaltrials.gov.
Authors: Steven D Nathan; Victor F Tapson; Jean Elwing; Franz Rischard; Jinesh Mehta; Shelley Shapiro; Eric Shen; Chunqin Deng; Peter Smith; Aaron Waxman Journal: Am J Respir Crit Care Med Date: 2022-01-15 Impact factor: 21.405