Clinical Characteristics and Management of Statin-Associated Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Immune-Mediated Necrotizing Myopathy

Abstract

Background: Immune-mediated necrotizing myopathy (IMNM) associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody is a rare but critical complication usually triggered by statin use. However, the comprehensive characterization and long-term outcomes of anti-HMGCR-positive IMNM remain underexplored. This study aimed to examine the clinical characteristics, diagnostic challenges, treatment responses, and long-term outcomes of patients with anti-HMGCR-positive IMNM. Methods: A retrospective review was conducted at a single institution between 2019 and 2025 to analyze the data of patients diagnosed with anti-HMGCR-positive IMNM. Diagnoses were confirmed by detecting anti-HMGCR antibodies and meeting the criteria for IMNM of the European Neuromuscular Center. The analyzed data included demographics, clinical presentation, laboratory findings, imaging results, muscle biopsy characteristics, treatment regimens, and follow-up outcomes. Results: Ten patients (six women and four men) with a median age of 58 (range, 33-86) years were included. Nine patients had a history of statin use for a median duration of two years. The average diagnostic delay was 233 days after the onset of symptoms. The initial creatine kinase (CK) levels ranged from 1438 to over 13,000 IU/L. Muscle biopsies revealed necrosis and regeneration of muscle fibers. CK levels fluctuated and trended downward over 180 days post-treatment. Treatment included corticosteroids, methotrexate, azathioprine, tacrolimus, mycophenolate, intravenous immunoglobulin, and rituximab. Delayed treatment initiation from symptom onset was correlated with prolonged treatment time until the first remission. Conclusions: The prognosis of anti-HMGCR-positive IMNM is less favorable when treatment is delayed after symptom onset. Further research is warranted to identify poor prognostic markers and develop relevant treatments.