Benefit of antifibrotic therapy initiated during acute exacerbation of interstitial lung disease: A systematic review

Abstract

Background: Acute exacerbations of interstitial lung disease (AE-ILD) are associated with significant morbidity and mortality. While corticosteroids are commonly used in the treatment, their optimal dose, duration, and overall benefit remain unclear. This systematic review evaluates the efficacy of antifibrotic medications (nintedanib and pirfenidone) when initiated during or immediately after AE-ILD.

Methods: We conducted a systematic search across MEDLINE, EMBASE, and Cochrane databases through January 2025. Studies comparing antifibrotic medications to standard care in AE-ILD were included. Primary outcomes were survival rates, hospitalization duration, and AE-ILD recurrence. Quality assessment was performed using the Newcastle-Ottawa Scale.

Results: Four observational studies from Japan comprising 6321 patients met the inclusion criteria. Nintedanib was associated with significantly reduced in-hospital mortality (7.1 % vs. 15.1 %, p < 0.001) and shorter hospitalization duration (30.7 ± 13.7 vs. 37.5 ± 19.0 days, p < 0.001) in one large study (n = 6235). A second nintedanib study demonstrated lower 90-day mortality (36.36 % vs. 54.55 %, p = 0.048) and delayed time to subsequent exacerbations. Two smaller studies evaluating pirfenidone showed trends toward improved 90-day survival that did not reach statistical significance (64.3 % vs. 52.9 %, p = 0.72; 44 % vs. 34 %, p = 0.391). Reported adverse events were consistent with known safety profiles of these medications.

Conclusion: Current evidence suggests nintedanib may reduce mortality and hospitalization duration in AE-ILD, while pirfenidone's benefits remain inconclusive. These findings are limited by the observational nature of the studies, variability in AE-ILD definitions, and limited geographical representation. Well-designed randomized controlled trials are needed to confirm these preliminary findings and establish optimal treatment protocols for AE-ILD.

Keywords: Acute exacerbation of interstitial lung disease; Antifibrotic therapy; Nintedanib; Pirfenidone.