Abstract
BACKGROUND: The development of rapidly progressive interstitial lung disease (RP-ILD) in patients with anti-MDA5-positive dermatomyositis-associated interstitial lung disease (MDA5+ DM-ILD) is a major cause of adverse outcomes, including mortality. This study aimed to identify factors influencing the occurrence of RP-ILD in patients with MDA5+ DM-ILD. METHODS: A systematic search was conducted in PubMed, EMBASE, the Cochrane Library, Web of Science, and Scopus for studies investigating factors associated with RP-ILD in MDA5+ DM-ILD, with the search period extending to January 1, 2026. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using Stata 18.0 software. RESULTS: Fifteen studies were included in the meta-analysis, all of which were of high quality, with an average NOS score of 7.9. The meta-analysis revealed that male sex (OR = 1.99, 95% CI: 1.27-3.12), advanced age (OR = 2.54, 95% CI: 1.40-4.60), disease duration <3 months (OR = 3.23, 95% CI: 2.23-4.70), fever (OR = 2.46, 95% CI: 1.55-3.90), anti-Ro52 antibody positivity (OR = 5.05, 95% CI: 3.21-7.96), elevated C-reactive protein (CRP) (OR = 2.29, 95% CI: 1.78-2.94), elevated neutrophil-to-lymphocyte ratio (NLR) (OR = 2.29, 95% CI: 1.28-4.08), elevated lactate dehydrogenase (LDH) (OR = 3.39, 95% CI: 2.20-5.22), elevated aspartate aminotransferase (AST) (OR = 1.03, 95% CI: 1.00-1.06), elevated alanine aminotransferase (ALT) (OR = 2.42, 95% CI: 1.22-4.80), elevated serum ferritin (SF) (OR = 3.81, 95% CI: 1.95-7.42), lymphopenia (OR = 2.14, 95% CI: 1.10-4.16), and elevated carcinoembryonic antigen (CEA) (OR = 3.38, 95% CI: 1.32-8.66) were risk factors for RP-ILD. Conversely, arthralgia/arthritis (OR = 0.26, 95% CI: 0.16-0.44) and lymphocytosis (OR = 0.17, 95% CI: 0.09-0.31) were identified as potential protective factors. CONCLUSION: This study explored potential risk and protective factors associated with the development of RP-ILD in patients with MDA5+ DM-ILD, providing a basis for early identification and management. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420261287925.