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Efficacy, safety, and tolerability of antifibrotic agents in rheumatoid arthritis-associated interstitial lung disease: A systematic review and meta-analysis

J. Narváez, Martí Aguilar-Coll, Montserrat Roig-Kim, Judith Palacios-Olid, Pol Maymó-Paituvi, Laia de Daniel Bisbe, Dídac LLop

Autoimmunity Reviews, 2025

11 citations

Abstract

OBJECTIVE

To evaluate the efficacy, safety, and tolerability of antifibrotic agents, nintedanib and pirfenidone, in the treatment of rheumatoid arthritis-associated interstitial lung disease (RA-ILD).

METHODS

A systematic literature review was conducted following PRISMA and MOOSE guidelines. Studies assessing nintedanib or pirfenidone in RA-ILD were included. A meta-analysis was performed using a random-effects model.

RESULTS

Six studies (2 randomized controlled trials and 4 observational) involving 270 RA-ILD patients met the inclusion criteria. In total, 148 received nintedanib and 122 received pirfenidone. Nearly 70 % had a usual interstitial pneumonia pattern. The pooled analysis revealed a mean FVC decline of -68.97 mL/year (95 % CI: -104.85 to -32.49; p < 0.001) and a mean difference of 1.15 % (p = 0.33; after excluding influential studies: -0.28, p = 0.54). Their impact on %pDLCO has been less extensively evaluated, with a mean difference of -1.76 % (p = 0.36; after excluding influential studies: effect size -3.78, p < 0.001). The changes in pulmonary function tests were comparable between nintedanib and pirfenidone. Mortality rates ranged from 15 % to 35 %, with respiratory-specific mortality reported at 44 % to 100 %. Lung transplantation rates were 4-5 %. Antifibrotic therapy was associated with a pooled adverse event (AE) rate of 73 % (95 % CI: 0.38-0.97; p < 0.001), with gastrointestinal symptoms and hepatotoxicity being the most frequently reported. Treatment…

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