Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Aug 26;24(12):103922.
doi: 10.1016/j.autrev.2025.103922. Online ahead of print.

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

A Fassio  1 , M Sebastiani  2 , F Pollastri  3 , F Cozzini  4 , C Crotti  5 , N Ughi  6 , E De Lorenzis  7 , S Mancuso  8 , M Radin  9 , G Carrara  10 , G Landolfi  10 , D Rozza  10 , A Manfredi  11
Affiliations
Free article
Review

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

A Fassio et al. Autoimmun Rev. .
Free article

Abstract

Background: rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). 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 from inception up to October 2023, followed by an update up to April 2025, with a pre-defined protocol. 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, and heterogeneity and publication bias were thoroughly assessed.

Results: sixty-nine studies encompassing 7879 RA-ILD patients were included. Treatments with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), 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. Antifibrotics, particularly nintedanib, demonstrated variable efficacy, while pirfenidone showed limited benefit. Safety profiles favored antifibrotics over csDMARDs/immunosuppressants regarding serious adverse events.

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 the safety of MTX and particularly support ABA, RTX, and nintedanib as promising options, while underscoring the need for further high-quality trials specifically in RA-ILD.

Keywords: Interstitial lung disease; Italian recommendations; Metanalysis; Rheumatoid arthritis.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Professor Marco Sebastiani has received consultancy fees, and/or speaker fees from Boehringer Ingelheim, outside the submitted work.

LinkOut - more resources