BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) demonstrate a range of lung function impairment. However, the efficacy of antifibrotics compared with placebo has not been assessed in patients with more advanced disease. This post-hoc analysis investigated the efficacy and safety of pirfenidone versus placebo in patients with IPF and more advanced lung function impairment, defined as percent predicted forced vital capacity (%FVC)<50% and/or percent predicted carbon monoxide diffusing capacity <35%. METHODS: Patients randomised to pirfenidone 2,403mg/day or placebo in the ASCEND (NCT01366209) and CAPACITY (NCT00287716; NCT00287729) trials with more advanced baseline lung function impairment (pirfenidone, n=90; placebo, n=80) were included. Mortality, lung function, hospitalisation, exercise capacity and dyspnoea were investigated over 52 weeks. RESULTS: At Week 52 versus placebo, pirfenidone was associated with significantly lower risks of all-cause mortality (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.09-0.86; p=0.0180), >/=10% absolute %FVC decline or all-cause mortality (HR 0.40; 95% CI 0.23-0.69; p=0.0006) and >/=10% absolute %FVC decline or respiratory-related hospitalisation or all-cause mortality (HR 0.46; 95% CI 0.28-0.76; p=0.0018). At Week 52, median treatment differences favouring pirfenidone were 36.7m for 6-min walk distance and -8.0 points for the University of California-San Diego Shortness of Breath Questionnaire total score. Treatment-emergent adverse events (TEAEs) led to discontinuation in 14.4% and 21.3% of patients with pirfenidone and placebo, respectively. CONCLUSION: Pirfenidone demonstrated clinically relevant benefits across multiple domains in patients with IPF and more advanced disease without an increased risk of discontinuation due to TEAEs. CLINICAL TRIALS REGISTRATION: clinicaltrials. gov (ASCEND: NCT01366209; CAPACITY: NCT00287716; NCT00287729).
- Nathan, S. D.
- Costabel, U.
- Albera, C.
- Behr, J.
- Wuyts, W. A.
- Kirchgaessler, K. U.
- Stauffer, J. L.
- Morgenthien, E.
- Chou, W.
- Limb, S. L.
- Noble, P. W.
Keywords
- *Dyspnoea
- *Idiopathic pulmonary fibrosis
- *Mortality
- *Pirfenidone