Pirfenidone may improve results for patients with non-IPF fibrotic ILDs: RELIEF


By Dave Levitan

7 Apr 2021

Pirfenidone yielded improved outcome over placebo in a trial of patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (IPF). However, though the results were significant, the trial was terminated early due to slow recruitment, leaving the use of this agent in non-IPF fibrotic ILDs still in question.

“Expert groups independent of the pharmaceutical industry now have a key role in making recommendations or providing informal guidance on the use of pirfenidone and nintedanib in ILDs other than IPF with the progressive fibrotic phenotype, based on existing data, clinical reasoning, and common sense,” wrote Prof Athol Wells, of Royal Brompton Hospital, in an editorial in The Lancet Respiratory Medicine.

Results from the RELIEF trial, led by Prof Jürgen Behr of Ludwig Maximillian University Munich, were published in the same journal. The trial enrolled a total of 127 patients with progression fibrotic ILD with four specific diagnoses: collagen or vascular diseases, fibrotic non-specific interstitial pneumonia, chronic hypersensitivity pneumonitis, or asbestos-induced lung fibrosis. They were randomised to receive either pirfenidone or placebo, and the trial was prematurely terminated after an interim analysis for futility triggered by slow recruitment.

After 48 weeks, the patients randomised to receive pirfenidone had a significantly lower decline in forced vital capacity (p = .043). The results were the same when stratified by diagnostic group.

The researchers used multiple imputation methods to confirm the results given the low recruitment, with no change seen.

There was one non-respiratory death in the pirfenidone group, and five deaths including three respiratory in the placebo group. The most frequent serious adverse events in both groups included infections and infestations (8% in pirfenidone group, 16% in placebo group), general disorders including disease worsening (3% and 11%, respectively), and cardiac disorders (2% and 8%, respectively).

The authors cautioned that the early termination of the trial does substantially limit its interpretation. “Nevertheless, analyses of the primary study endpoint – including those with the prespecified imputation methods for missing values as well as additional post-hoc imputation models – showed a treatment effect,” they wrote.

Prof Wells agreed that at its root this was a positive trial, in spite of the limited power due to early termination and slow recruitment. He stressed that with the results from RELIEF, as well as earlier results from the INBUILD trial, can still help guide clinical practice.

“This is not a situation in which there is insufficient evidence to allow guideline and other groups to help clinicians, for whom the use or non-use of pirfenidone is equally a management decision,” he wrote. “Expert group recommendations, whether made formally or as a statement of usual practice of expert group members, are most helpful when evidence is marginal but highly suggestive.”

Pirfenidone is currently indicated in Australia for the treatment only of IPF, but not for non-IPF pathologies. “This is when clinicians most need guidance in routine practice,” Prof Wells wrote.

The study was funded by the German Center for Lung Research as well as Roche Pharma; Genentech is a subsidiary of Roche, and markets pirfenidone. Prof Behr and other co-authors report receiving personal fees, grants, honoraria, and other financial and non-financial support from Roche as well as several other pharmaceutical companies.

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