2050: Efficacy and Safety of Antifibrotic Therapy in Autoimmune–Associated Interstitial Lung Disease: A Meta-Analysis

Background/Purpose: Autoimmune–associated interstitial lung disease (A‑ILD) which includes Rheumatoid arthritis associated interstitial lung disease (RA-ILD), Systemic Sclerosis associated interstitial lung disease (SS-ILD), and others is a progressive fibrosing lung disease, which is associated with substantial morbidity and mortality. Modern treatment strategies rely on immunosuppression but many individuals develop progressive fibrosis. The antifibrotic agents pirfenidone and nintedanib which are approved for use in idiopathic pulmonary fibrosis, now are being studied as possible therapies for inhibiting fibrosis in A‑ILD. We performed meta‑analysis to evaluate the safety and efficacy of antifibrotic therapy in A‑ILD.

Methods: We systematically searched PubMed, Embase, Cochrane for English-language studies involving patients being treated with antifibrotic agents, and reported at least one relevant outcome. Three studies met inclusion criteria. Data were pooled using the inverse variance weighting method with a random-effects model in R Studio. Confidence intervals and heterogeneity were assessed, and forest plots were generated to visualise the pooled effect estimates.

Results: Three studies involving 868 patients with A-ILD were included. Analysis of antifibrotic agents demonstrated significant reduction in annual FVC decline rate (MD=63.4 ml/yr, 95% CI: 26.40–100.44, p< 0.01). The risk of experiencing >10% predicted FVC decline at week 52 was lower with antifibrotic therapy, though not statistically significant (RR=0.80, 95% CI: 0.48–1.33, p=0.39). Serious adverse events were comparable between groups (RR=1.10, 95% CI: 0.87–1.39, p=0.44), but antifibrotic therapy showed significantly higher discontinuation rates due to adverse events (RR=1.89, 95% CI: 1.32–2.71, p< 0.01).

Conclusion: Antifibrotic treatment slowed the annual FVC decline in A-ILD patients and had similar rates of serious adverse events compared to placebo. But the treatment discontinuation rates due to adverse events were higher with Antifibrotic agents. This suggests that antifibrotics provide benefit for A-ILD patients, but they have to be monitored closely due to adverse events.