PO:06:086 | Updated Systematic Literature Review and meta-analysis to Inform the Italian Society of Rheumatology Recommendations on the Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease

Angelo Fassio¹, Marco Sebastiani^9|10, Francesco Pollastri¹, Chiara Crotti⁴, Nicola Ughi⁵, Enrico De Lorenzis⁶, Silvia Mancuso⁷, Massimo Radin⁸, Francesca Cozzini⁹, Greta Carrara¹¹, Gianpiero Landolfi¹¹, Roberto Rozza¹¹, Andreina Manfredi^2|3 | ¹Rheumatology Unit, University of Verona, Verona, Italy; ²University of Modena and Reggio Emilia, Reggio Emilia, Italy; ³Rheumatology Unit, AUSL-IRCCS, Reggio Emilia, Italy; ⁴Bone Disease Unit, Department of Rheumatology and Medical Science, ASST-G.Pini-CTO, Milan, Italy; ⁵Division of Rheumatology, Multispecialist Medical Department, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; ⁶Department of Aging Diseases, Orthopedic and Rheumatology, Rheumatology Division, P. Gemelli, Roma, Italy; ⁷Rheumatology Unit, Department of Clinical, Internal, Anaesthesiologic and Cardiovascular, Sciences, Sapienza, Roma, Italy; ⁸CMID, San Giovanni Bosco Hub Hospital ASL Città di Torino and Department of Clinical and Biological Sciences, Turin, Italy; ⁹Department of Medicine and Surgery, University of Parma, Parma, Italy; ¹⁰Rheumatology Unit, AUSL Piacenza, Piacenza, Italy; ¹¹Unità Epidemiologica, SIR, Società Italiana di Reumatologia, Milano, Italy

Background. rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA), contributing significantly to morbidity and mortality. Despite recent guideline initiatives, no treatment recommendations specifically tailored to RA-ILD have been developed in Italy. This systematic literature review (SLR) and meta-analysis was conducted to inform the Italian Society of Rheumatology (SIR) national recommendations for the management of RA-ILD.

Methods. We conducted a systematic review and meta-analysis of studies evaluating pharmacological interventions for RA-ILD up to April 2025, following a pre-defined protocol (PRISMA flow in Figure 1). Eligible studies included randomized controlled trials, cohort studies, and case series reporting pulmonary function outcomes, radiological progression, adverse events, and mortality. Meta-analyses were performed using random-effects models, and heterogeneity and publication bias were thoroughly assessed.

Results. sixty-seven studies encompassing 7384 RA-ILD patients were included. Treatments with rituximab (RTX), mycophenolate mofetil (MMF), abatacept (ABA), and Janus kinase inhibitors (JAKi) were associated with stabilization or improvement of forced vital capacity (FVC). Methotrexate (MTX) was associated with reduced risk of ILD progression and mortality. Conversely, tumour necrosis factor inhibitors (TNFi) were linked to increased risk of progression. Antifibrotics, particularly nintedanib, demonstrated variable efficacy, while pirfenidone showed limited benefit. Safety profiles favored antifibrotics over csDMARDs/immunosuppressants regarding serious adverse events. The data for each treatment analyzed are presented in Figure 2: the treatment-specific subgroup %FVC change (treatment users vs. non-users) is shown in Figure 2a, while the treatment-specific subgroup ORs for mortality is shown in Figure 2b.

Conclusions. this SLR provides an updated synthesis of evidence on RA-ILD treatments, supporting the forthcoming SIR recommendations. Despite inherent limitations of observational studies and heterogeneity, the data highlight MTX, ABA, RTX, and MMF as promising options, while underscoring the need for further high-quality trials specifically in RA-ILD.