Pirfenidone in Bronchiolitis Obliterans Syndrome After Bilateral Lung Transplantation: A Europea

• The study investigates pirfenidone, an antifibrotic agent, for progressive bronchiolitis obliterans syndrome (BOS) within chronic lung allograft dysfunction (CLAD) after bilateral lung transplantation.
• The aim was to assess whether pirfenidone could slow decline in lung function, specifically FEV1, relative to placebo when added to standard care.

They were randomised 1:1 to pirfenidone or placebo, in addition to standard care, for 26 weeks.

• This was an investigator-initiated, international, multicentre, randomized, double-blind, placebo-controlled phase II trial conducted across nine European lung transplant centers.
• Participants were adults with bilateral lung transplants and progressive BOS.
• The primary endpoint was change in FEV1 from baseline to week 26, with imputation for missing data.

• Screening identified 477 potential participants; 90 were randomized (pirfenidone n=48; placebo n=42).
• Pirfenidone dosing was 2403 mg per day, delivered in divided doses, with concomitant standard care.

• Both groups demonstrated ongoing FEV1 decline from baseline through week 26.
• There was no significant difference between pirfenidone and placebo across intention-to-treat analyses, ITT with imputation, or per-protocol analyses.
• Secondary outcomes, including graft loss, death, and re-transplantation, were similar between groups.
• Treatment-related serious adverse events occurred with similar frequency in both arms.

• Pirfenidone did not demonstrate superiority over placebo plus standard care for progressive BOS in this exploratory trial.
• The study underscores the need for alternative strategies to address BOS/CLAD after lung transplantation.