Accepted for/Published in: JMIR Research Protocols
Date Submitted: Feb 27, 2025
Date Accepted: Jun 20, 2025
Anti-Inflammatory versus Antifibrotic Therapies for the Management of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Protocol for a Systematic Review and Meta-Analysis
ABSTRACT
Background:
Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD) is a significant extra-articular manifestation of rheumatoid arthritis (RA), characterized by progressive lung fibrosis and inflammation, leading to increased morbidity and mortality. While anti-inflammatory therapies have traditionally been used to manage RA-ILD, emerging evidence suggests that antifibrotic therapies may also offer clinical benefits. This protocol outlines a systematic review and meta-analysis to compare the safety and efficacy of antifibrotic versus anti-inflammatory therapies in the management of chronic RA-ILD.
Objective:
This study aims to evaluate and compare the impact of antifibrotic and anti-inflammatory therapies on lung function, radiologic progression, clinical outcomes, and safety in patients with chronic RA-ILD.
Methods:
A systematic search will be conducted across PubMed, Embase, and the Cochrane Library, following PRISMA guidelines. Eligible studies will include adult patients (≥18 years) diagnosed with RA-ILD and treated with either antifibrotic or anti-inflammatory therapies. Primary outcomes include pulmonary function parameters—forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and diffusing capacity of the lungs for carbon monoxide (DLCO). Secondary outcomes include radiological changes (e.g., fibrosis progression on high-resolution computed tomography), clinical endpoints (e.g., disease progression rates, overall survival, quality of life), and safety and tolerability of therapies. Pooled effect estimates will be calculated using random-effects meta-analysis, and heterogeneity will be assessed via Cochran’s Q test and I² statistic.
Results:
Initial search strategies and database queries were developed and executed in August and September 2024. Title and duplicate screening began in October 2024, followed by abstract screening in December 2024 and January 2025. Full-text screening is scheduled for completion by March 2025, with data extraction and risk of bias assessment planned for April and May 2025. The final analysis will be conducted in June 2025, followed by manuscript drafting and submission to peer-reviewed journals by August 2025. The results of this systematic review will provide comparative efficacy and safety profiles of antifibrotic and anti-inflammatory therapies, offering critical insights for clinicians managing chronic RA-ILD.
Conclusions:
The findings will address critical gaps in the management of RA-ILD, offering evidence-based recommendations for therapeutic decision-making and improving outcomes for patients with this debilitating condition. Clinical Trial: The study protocol has been registered with PROSPERO (CRD42024583847). Registration Link: https://www.crd.york.ac.uk/prospero/export_details_pdf.php
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