Effect of targeted therapies on pulmonary function in rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.

INTRODUCTION

Interstitial lung disease (ILD) is a serious extra-articular manifestation of rheumatoid arthritis (RA) associated with increased morbidity and mortality. The pulmonary safety of biologic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in RA-associated ILD (RA-ILD) remains uncertain. This systematic review and meta-analysis aimed to assess the effect of bDMARDs and tsDMARDs on ILD progression in RA, focusing on pulmonary function test (PFT) parameters-forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO)-and, when available, high-resolution computed tomography (HRCT) outcomes.

METHODS

PubMed and Cochrane databases were searched up to 2025 for controlled trials and observational studies, including patients with RA fulfilling the 1987 ACR or 2010 ACR/EULAR criteria. Studies reporting longitudinal changes in PFTs or HRCT after bDMARD or tsDMARD treatment were included. Meta-analyses were conducted using the inverse variance method (RevMan V.5.4.1) for pooled estimates of FVC and DLCO.

RESULTS

18 observational studies including 958 patients (mean age 65 years; 57% female) were analysed. The most frequent ILD patterns were usual interstitial pneumonia (48%) and nonspecific interstitial pneumonia (40%). Data were available for rituximab (six studies), abatacept (4), JAK inhibitors (4), tumour necrosis factor (TNF) inhibitors (1) and tocilizumab (1). Pooled analysis showed no significant overall change in FVC (mean difference -0.85%, 95% CI -2.40 to 0.71; p=0.29) or DLCO (+0.79, 95% CI -0.30 to 1.88; p=0.16).

CONCLUSION

bDMARDs and tsDMARDs appear to stabilise pulmonary function in RA-ILD, without significant differences between agents. Further prospective studies integrating PFT and HRCT endpoints are needed to better define their pulmonary safety and long-term effects.