Systemic Sclerosis-Associated Myopathy in a Large Single-Center Cohort: Autoantibody Profiles, Histologic Features, and Independent Risk of Death.

Abstract

Skeletal myopathy is common in systemic sclerosis (SSc), but its associated clinical manifestations and long-term outcomes are poorly characterized. The purpose of this study is to characterize patients with skeletal myopathy and define its impact on survival. This retrospective cohort study included patients in the Johns Hopkins Scleroderma Center Research Registry with and without skeletal myopathy. Clinical data including autoantibody profiles and muscle histopathology were compared between those with and without myopathy. Survival analyses including Cox proportional hazards and regression analyses were performed. In the cohort, 672 (17%) of 3,919 patients had a skeletal myopathy. When compared to those without a myopathy, those with myopathy were more commonly of the diffuse subtype (60.4% vs 32.6%, P < 0.0001), African American (30.4% vs 13.9%, P < 0.0001), and with shorter disease duration at first visit (mean 4.52 ± SD 6.2 years vs mean 6.5 ± SD 8.0 years, P < 0.00001). Anti-PM-Scl, U3-RNP, and anti-Ku were associated with the presence of myopathy, whereas anticentromere was protective against myopathy. Myopathy was associated with an increased risk of death in univariate Cox regression analyses (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.40-1.81, P < 0.0001). In multivariate Cox proportional regression analyses, myopathy had an independent risk of death even after controlling for other confounders (HR 1.60, CI 1.32-1.93, P < 0.0001). Skeletal myopathy in SSc is associated with distinct clinical and autoantibody profiles, as well as independently increased risk of death. These findings highlight the importance of early detection and further investigation into how myopathy predicts patient outcomes, with the goal of improving targeted therapies and survival in this high-risk population.