Ezetimibe/bempedoic acid combination in statin-induced anti-HMGCR positive immune-mediated necrotizing myopathy: a case series.

Abstract

Immune-mediated necrotizing myopathy (IMNM) is a rare but potentially life-threatening complication of statins. Subsequent management of dyslipidemia is challenging, since data on the safety and effectiveness of non-statin lipid-lowering therapies (LLT) are sparse. Ezetimibe (EZ) is considered safe, but its cholesterol-lowering potential is limited, and most patients do not achieve treatment targets. Bempedoic acid (BA) targets a different enzyme, ATP-citrate lyase, therefore bypassing the risk of triggering autoimmune responses against 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). We present the first case series evaluating the safety and effectiveness of the combination of EZ/BA in patients with statin-induced anti-HMGCR positive IMNM. Six patients with anti-HMGCR positive IMNM treated with EZ/BA were followed longitudinally. CK, LDL-cholesterol and muscle strength were assessed at predefined intervals, before and after EZ/BA initiation. At diagnosis, the mean age was 59±10 years and mean CK was 7166±3700 U/L. Patients were followed for a median of 10 months (IQR 4-21) after non-statin LLT initiation. None experienced a relapse. Mean manual muscle testing scores (MMT8) at EZ/BA initiation and last follow-up were 141±17 and 141±17, respectively (P = 0.77). Mean CK levels were 333±258 and 364±400 U/L, respectively (P = 0.66). All patients responded well to EZ/BA with improved mean LDL-cholesterol [133±27 to 82±17 mg/dL (p < 0.05)] at last follow-up. EZ/BA combination therapy appears safe and effective in patients with statin-induced IMNM. However, confirmation through longer follow-up and validation in multicenter cohorts is required before recommendation as a viable alternative to statins is appropriate.