Marked Long-Term Improvement in Lung Function in Melanoma Differentiation-Associated Protein 5 Antibody-Positive Dermatomyositis Patients: Experience of a Single-Center Longitudinal Cohort in North America.

Abstract

The objective of this study was to describe the longitudinal disease course and pulmonary outcomes of North American patients with melanoma differentiation-associated protein 5 (MDA5) antibody-associated dermatomyositis (DM). Thirty patients with MDA5 antibody-associated DM were identified in a single-center longitudinal cohort of 352 patients with idiopathic inflammatory myopathies. Longitudinal assessments of patient clinical and laboratory disease characteristics, pulmonary function tests (PFT), and high-resolution computed tomography chest scans were conducted. Eighty percent (n = 24/30) of patients with MDA5 antibody-associated DM had interstitial lung disease (ILD). The overall mortality was low (2/24 at a mean ± SD follow-up of 4.0 ± 0.8 years). At this follow-up, patients were receiving 3.1 ± 1.3 therapies, including 79% receiving intravenous Ig (IVIg), 58% receiving rituximab, 67% receiving mycophenolate, and 63% receiving glucocorticoids. In 18 of 22 surviving patients with ILD who had two-year longitudinal follow-up available at 1.8 ± 0.6 years, improvements of 16% and 17% predicted forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) were noted. In 10 of 18 patients with additional long-term follow-up available (mean ± SD 6.8 ± 3.4 years), improvements of 24% and 20% predicted FVC and DLco were noted. MDA5 antibody and interleukin-15 (IL-15) levels and paraoxonase 1 (PON1) enzyme activity correlated significantly with disease activity at baseline and longitudinally. In a North American MDA5 antibody-associated DM-ILD cohort treated with aggressive combination immunomodulatory therapy including predominantly mycophenolate, IVIg, and rituximab, disease mortality was low and lung function improved markedly. IL-15, PON1, and MDA5 antibody titers warrant further investigation as disease activity biomarkers in this high-risk population.