Distinct phenotype and prognosis of immune-mediated necrotizing myopathy based on clinical-serological-pathological classification

Abstract Objective The aim of the study was to investigate the characteristics and prognosis of patients with immune-mediated necrotizing myopathy (IMNM) based on clinical, serological and pathological classification. Methods A total of 138 patients with IMNM who met the 2018 European Neuromuscular Center criteria for IMNM including 62 anti-SRP, 32 anti-HMGCR-positive and 44 myositis-specific antibody–negative were involved in the study. All patients were followed up and evaluated remission and relapse. Clustering analysis based on clinical, serological and pathological parameters was used to define subgroups. Results Clustering analysis classified IMNM into three clusters. Cluster 1 patients (n = 35) had the highest creatine kinase (CK) levels, the shortest disease course, severe muscle weakness and more inflammation infiltration in muscle biopsy. Cluster 2 patients (n = 79) had the lowest CK level and moderate inflammation infiltrate. Cluster 3 patients (n = 24) had the youngest age of onset, the longest disease course and the least frequency of inflammatory infiltration. Patients in cluster 3 had the longest time-to-remission [median survival time: 61 (18.3, 103.7) vs 20.5 (16.2, 24.9) and 27 (19.6, 34.3) months] and shorter relapse-free time than those in cluster 1 and 2 [median remission time 95% CI 34 (19.9, 48.0) vs 73 (49.0, 68.7) and 73 (48.4, 97.6) months]. Patients with age of onset >55 years, more regeneration of muscle fibres, more CD4+ T infiltration and membrane attack complex deposition had more favourable outcomes regarding time to achieving remission. Conclusions Stratification combining clinical, serological and pathological features could distinguish phenotypes and prognosis of IMNM. The pathological characteristics may impact the long-term prognosis of patients with IMNM.