A European multicentre, randomised controlled trial of pirfenidone in bronchiolitis obliterans syndrome after bilateral lung transplantation

Clinical Snapshot

Key Findings

• P Value: Not significant (exact value not reported)

• Effect Size: No significant difference between groups

• Primary Outcome: Change in FEV1 from baseline to week 26

• Nnt Or Sensitivity: Not applicable - no treatment benefit demonstrated

• Confidence Interval: Not reported in abstract

Clinical Application

Limited by pirfenidone cost and lack of demonstrated efficacy Results relevant to Australian lung transplant programs; pirfenidone available on PBS for IPF but not indicated for BOS based on this evidence Adults with bilateral lung transplants and progressive BOS in Australian transplant centres

Abstract

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a major obstacle to improving outcomes after lung transplantation. Bronchiolitis obliterans syndrome (BOS), characterised by progressive decline in forced expiratory volume in 1 s (FEV1) due to fibrotic scarring of the small airways, accounts for most CLAD cases. Pirfenidone, an antifibrotic agent used for idiopathic pulmonary fibrosis, was assessed for treating progressive BOS. METHODS: An investigator-initiated, international, multicentre, randomised, double-blind, placebo-controlled phase II trial was conducted in nine European lung transplant centres. Adults with bilateral lung transplants and progressive BOS were randomised (1:1) to receive pirfenidone 2403 mg·day-1 or placebo with standard care for 26 weeks. The primary end-point was change in FEV1 from baseline to week 26, with imputation for missing values. FINDINGS: From 1 May 2015 to 1 December 2019, 477 patients were screened, and 90 were randomised to pirfenidone (n=48) or placebo (n=42). Both groups showed continued decline in FEV1 from baseline to week 26, with no significant difference in intention to treat (ITT), ITT with imputation, or per-protocol analyses. Secondary end-points (graft loss, death, re-transplantation) were similar between groups. Treatment-related serious adverse events were distributed equally. INTERPRETATION: Pirfenidone did not show superiority over placebo and standard care in this exploratory trial. It cannot be recommended for treating BOS. Further research is needed to explore other treatments for CLAD to improve long-term outcomes after lung transplantation.

References

1. 1.Perch, M., Corris, P., Lordan, J., Bessa, V., Magnusson, J., Verleden, G. M., Vos, R., Kneidinger, N., Leuckfeld, I., Verschuuren, E., & Gottlieb, J. (2026). A European multicentre, randomised controlled trial of pirfenidone in bronchiolitis obliterans syndrome after bilateral lung transplantation. European Respiratory Journal. https://doi.org/10.1016/j.healun.2024.05.013