To investigate the characteristics of different clinico-serologic subgroups of immune-mediated necrotizing myopathy (IMNM).

We retrospectively reviewed data from medical charts of 64 patients diagnosed with IMNM between 2012 and 2017 in 3 neuromuscular referral centers in The Netherlands and 1 in Belgium.

Seventeen patients had anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies (Abs), of whom 11 had a history of statin use, 15 had anti-signal recognition particle (SRP) Abs, 2 had anti-melanoma differentiation-associated protein 5 (MDA5) Abs, 22 patients were seronegative, and 9 patients did not have a complete Ab assessment. Moderate to severe disability in HMGCR Ab-positive and anti-SRP Ab-positive IMNM was common (71% and 60%, respectively) despite multimodality treatment. Compared with statin-associated anti-HMGCR Ab-positive IMNM, statin-naive anti-HMGCR Ab-positive IMNM patients were more often men (67% vs 45%), had lower rates of dysphagia (17% vs 45%), and more frequently had third-line therapy (50% vs 9%) and poor to fatal outcome (50% vs 0%). Compared with seropositive IMNM, seronegative IMNM was characterized by female predominance (1:3), frequent occurrence of associated connective tissue disorders (22% vs 9%), and significantly higher rates of extramuscular disease activity (50% vs 16%, 0.014; 2-sided Fisher exact), also after excluding patients with an associated connective tissue disease (35% vs 7%, 0.038; 2-sided Fisher exact).

Our findings indicate that seronegative IMNM forms a subgroup with distinctive features from seropositive IMNM.