Increasing recognition of statin-associated anti-HMGCR antibody-positive autoimmune myopathy: a single-center retrospective study.

OBJECTIVE: The use of statins, which are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) enzyme, may in rare cases be associated with immune-mediated necrotizing myopathy. This condition is characterized by the presence of autoantibodies directed against the HMGCR enzyme. Previously considered very rare, the incidence of this myopathy diagnosis has markedly increased in our rheumatology unit over the past years. METHODS: We conducted a retrospective analysis of 13 patients diagnosed with statin-associated anti-HMGCR antibody (Ab)-positive immune-mediated necrotizing myopathy (anti-HMGCR-IMNM) over the 5-year period (June 2020-May 2025) at the Turku University Hospital's rheumatology department serving 490,000 inhabitants. RESULTS: Patients presented with elevated creatine kinase (CK) levels, positive anti-HMGCR-Ab, proximal muscle weakness, and the initial symptom was usually difficulty walking. No other myositis autoantibodies were detected and extra-myopathic symptoms were rare. Most patients responded to immunosuppressive therapy including glucocorticoids, methotrexate or azathioprine, and rituximab with a more severe disease course. Disease severity ranged from mild to fatal. The incidence of statin-associated anti-HMGCR-IMNM was 5.3 cases per million per year, approximately 2.75 per 100,000 statin users per year, higher than previously reported. CONCLUSION: Statin-associated anti-HMGCR-IMNM is a rare but increasingly recognized condition requiring early diagnosis and immunosuppressive treatment. The clinical presentation is highly variable. Treatment and its intensity must be tailored individually, taking into account the patient's comorbidities and treatment related risks. Key Points • Anti-HMGCR antibody-positive immune-mediated necrotizing myopathy (anti-HMGCR-IMNM) may be triggered by statins, one of the most commonly prescribed classes of medications. Because delayed diagnosis may lead to significant morbidity, it is important that clinicians are familiar with this rare myopathic disorder. • Previously, statin-associated anti-HMGCR-IMNM was considered a very rare diagnosis. However, the incidence of this diagnosis appears to have increased markedly over recent years. • The apparent increase in diagnoses may be attributable to the growing use of statins; additionally, improved recognition and awareness of the disease may also partially explain this rise. • Rituximab may be an alternative in selected cases where the disease course is neither rapidly progressive nor life-threatening, although further research is needed.