RT Journal Article
SR Electronic
T1 Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: integrated analysis of cumulative data from 5 clinical trials
JF BMJ Open Respiratory Research
JO BMJ Open Resp Res
FD British Thoracic Society
SP e000105
DO 10.1136/bmjresp-2015-000105
VO 3
IS 1
A1 Lisa Lancaster
A1 Carlo Albera
A1 Williamson Z Bradford
A1 Ulrich Costabel
A1 Roland M du Bois
A1 Elizabeth A Fagan
A1 Robert S Fishman
A1 Ian Glaspole
A1 Marilyn K Glassberg
A1 Talmadge E King, Jr
A1 David J Lederer
A1 Zhengning Lin
A1 Steven D Nathan
A1 Carlos A Pereira
A1 Jeffrey J Swigris
A1 Dominique Valeyre
A1 Paul W Noble
YR 2016
UL http://bmjopenrespres.bmj.com/content/3/1/e000105.abstract
AB Background Pirfenidone is an oral antifibrotic agent that has been shown to reduce the decline in lung function in patients with idiopathic pulmonary fibrosis (IPF). We performed an integrated analysis of safety data from five clinical trials evaluating pirfenidone in patients with IPF.Methods All patients treated with pirfenidone in the three multinational Phase 3 studies (CAPACITY (studies 004 and 006), ASCEND (study 016)) and two ongoing open-label studies (study 002 and study 012 (RECAP)) were included in the analysis. Safety outcomes were assessed during the period from the first dose until 28 days after the last dose of study drug.Results A total of 1299 patients were included in the analysis. The cumulative total exposure to pirfenidone was 3160 person exposure years (PEY). The median duration of exposure was 1.7 years (range 1 week to 9.9 years), and the mean (±SD) daily dose was 2053.8 (±484.9) mg. Gastrointestinal events (nausea (37.6%), diarrhoea (28.1%), dyspepsia (18.4%), vomiting (15.9%)) and rash (25.0%) were the most common adverse events; these were generally mild to moderate in severity and without significant clinical consequence. Elevations in alanine aminotransferase or aspartate aminotransferase greater than three times the upper limit of normal occurred in 40/1299 (3.1%) patients (adjusted incidence, 2.3 per 100 PEY). Elevations were generally transient and reversible with dose modification or discontinuation.Conclusions A comprehensive analysis of safety outcomes in a large and well-defined cohort of 1299 patients with IPF who were followed prospectively for up to 9.9 years demonstrated that long-term treatment with pirfenidone is safe and generally well tolerated.Trial registration numbers NCT00287716, NCT00287729, NCT00662038, NCT01366209.