Anti-Melanoma Differentiation-Associated Protein 5 Antibody and the Risk of Rapidly Progressive Interstitial Lung Disease in Patients with Dermatomyositis: A Systematic Review and Meta-Analysis

Background: To assess the diagnostic accuracy and clinical utility of anti-melanoma differentiation-associated protein 5 (anti-MDA5) antibodies for identifying rapidly progressive interstitial lung disease (RP-ILD) in patients with classic dermatomyositis (CDM) and clinically amyopathic dermatomyositis (CADM). Methods: We searched PubMed, Ovid MEDLINE, and Embase from 1 January 1991 to 31 January 2022. Risk of bias was assessed using QUADAS-2. Studies with a complete 2 × 2 diagnostic table were synthesized using a bivariate random-effects generalized linear mixed model with exact binomial likelihood, and the equivalent hierarchical summary receiver operating characteristic (HSROC) curve was derived. Prespecified subgroup analyses, leave-one-out and study-exclusion sensitivity analyses, univariable bivariate meta-regression, and Deeks’ funnel-plot asymmetry test were performed. Results: Seventeen studies with complete 2 × 2 data (1528 patients; 261 with RP-ILD) entered the quantitative synthesis. The bivariate summary sensitivity was 75.8% (95% CI, 59.7–86.8%) and specificity was 88.5% (95% CI, 84.4–91.6%). The derived LR+ was 6.57 (95% CI, 4.59–9.38), LR− was 0.27 (95% CI, 0.16–0.48), and DOR was 24.0 (95% CI, 10.6–54.5). The 95% prediction intervals were wide for both sensitivity (22.8–97.1%) and specificity (68.7–96.4%), indicating substantial between-study variation. Among patients with RP-ILD, 99/261 (37.9%) were anti-MDA5 antibody negative. Prespecified meta-regressions did not show a significant joint covariate effect, and Deeks’ funnel-plot asymmetry test did not detect evidence of small-study effects (p = 0.276). Conclusions: Anti-MDA5 antibody positivity is associated with a substantially increased likelihood of RP-ILD and provides relatively high specificity, but its sensitivity is insufficient to exclude RP-ILD when the antibody is negative. Anti-MDA5 testing may therefore support early risk stratification as an adjunct to clinical and radiologic assessment rather than serve as a stand-alone diagnostic or prognostic marker.