Support for continued pirfenidone treatment in patients with IPF progression
medwireNews: Patients with idiopathic pulmonary fibrosis (IPF) who have previously experienced disease progression whilst receiving pirfenidone may benefit from continued treatment with the antifibrotic agent, researchers report.
In a post-hoc analysis of data from the ASCEND and CAPACITY trials, Steven Nathan (Inova Fairfax Hospital, Falls Church, Virginia, USA) and colleagues demonstrated that 23.6% of 1247 patients treated with pirfenidone 2403 mg/day or placebo experienced more than one disease progression event – defined as at least a 10% decline in percent predicted forced vital capacity (FVC), a 50 m or greater reduction in 6-minute walk distance (6MWD), respiratory hospitalisation or all-cause death – over 1 year of treatment.
As reported in Chest, 17.0% of 623 patients in the pirfenidone group and 30.1% of the 624 patients given placebo experienced two or more progression events, translating into a significant 47% reduced risk of a second progression event among those receiving pirfenidone.
The most commonly occurring sequences of progression events in the pirfenidone and placebo groups were a decline in 6MWD followed by FVC (13.2 vs 14.4%), a decrease in FVC followed by 6MWD (12.3 vs 13.8%), two successive decreases in 6MWD (9.4 vs 6.4%) and respiratory-related hospitalisation followed by death (3.8 vs 5.3%).
In all, 22 patients in the pirfenidone group and 42 participants given placebo died during follow-up, and “[t]he number of deaths increased with the number of preceding disease progression events, most notably in the placebo arm”, say Nathan and colleagues.
They found that a significantly smaller number of patients treated with pirfenidone versus placebo died following at least one progression event, with corresponding rates of 2.1% and 6.3%, and the majority of deaths in both groups were preceded by hospitalisation for respiratory-related causes.
Together, these exploratory findings “suggest that continued treatment with pirfenidone confers a benefit despite the occurrence of any single disease progression event”, write the researchers.
They add that in contrast to previous investigations “with single events defining disease progression”, the present study “provides a more global assessment of the benefits of pirfenidone therapy”, and a similar multiple-event endpoint in clinical trials “could provide a more complete characterization of a drug’s efficacy”.
The team concludes that “this analysis provides a basis for further exploration of new disease progression endpoints for potential use in future clinical trials, which will invariably include standard-of-care control arms with many patients receiving established antifibrotic therapy.”
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