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

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 discontinuation due to AEs occurred in nearly 24 % of patients (95 % CI: 0.16–0.40; p < 0.001).

Conclusion

Antifibrotic agents demonstrated stabilization of %pFVC, with less robust evidence for %pDLCO in RA-ILD. Nearly one quarter of patients discontinued therapy due to AEs.