Spontaneous remission in statin-associated HMGCR-positive immune-mediated necrotizing myopathy after statin withdrawal

Immune-mediated necrotizing myopathy (IMNM) associated with antibodies against 3‑hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is typically a severe autoimmune myopathy requiring immunosuppressive therapy. Rare spontaneous remissions after discontinuation of statins have been reported, suggesting that the disease course may be more heterogeneous than previously assumed. We retrospectively identified four patients with anti-HMGCR-positive IMNM who experienced full recovery without immunosuppressive treatment. All had developed proximal muscle weakness and markedly elevated creatine kinase levels (8-80 times the upper limit of normal) during statin therapy, and they fulfilled the histopathological criteria of IMNM, except for the p62-pattern. After statin withdrawal, all patients recovered within 6-12 months without specific treatment. Two later relapsed after statin re-exposure and again improved after statin discontinuation. One patient relapsed after a flu-like illness. During long-term follow-up of up to ten years, three patients remained asymptomatic, two despite persistently elevated antibody titers, and one patient was started on intravenous immunoglobulins. These findings indicate that a subset of anti-HMGCR IMNM may follow a self-limited or relapsing-remitting course. While these cases broaden the clinical spectrum of anti-HMGCR IMNM, their implications for management remain uncertain and warrant further investigation.