The incidence of anti-HMGCR immune-mediated necrotising myopathy: an Australian and UK retrospective multi-site cohort study

Objectives:
Immune-mediated necrotising myopathy (IMNM) with autoantibodies targeting 3-hydroxy-3-methylglutaryl-CoA reductase (anti-HMGCR) is considered a rare complication of statin therapy. We calculate the incidence of anti-HMGCR IMNM and describe clinical characteristics in four independent cohorts: Manchester (UK), Bristol (UK), Western Australia (WA, Australia) and South Australia (SA, Australia).

Methods:
Adults (≥18 years) with anti-HMGCR IMNM (ENMC criteria; 2018-2023) were identified from myositis clinic and laboratory records. Nationwide UK anti-HMGCR testing was performed at Oxford University Hospital Laboratories and state-based WA/SA testing at PathWest Laboratories.

Results:
109 anti-HMGCR IMNM cases were identified (51% female, median 66 years [IQR 58-72.2]) with median follow-up 2.3 years [IQR 1.5-4.2]. Mean annual incidence was 2.9 cases/million person-years. In statin-users, incidence was 20.4 (UK) and 24.1 (WA/SA) cases/million statin-users.
101 (92.7%) patients were statin-exposed, mostly atorvastatin (77/101, 76.2%). Median statin duration before IMNM diagnosis was 3 years (range: 1 month-23 years). Eight (7.5%) were statin-naïve and compared with statin-exposed patients, younger (median 46.1 vs. 67 years, p=0.02), frequently of non-white ethnicity (5/8 vs 20/77, p=0.04) and more commonly had dysphagia (4/8 vs 14/94, p=0.03). The median peak creatine kinase (CK) was 7,020 IU/L (range: 964-39,076). 48/105 (45.7%) received intravenous immunoglobulin. At follow-up, less than half had normal CK (50/105 [47.6%]) or muscle power (48/104 [46.2%]).

Conclusion:
For the first time, we have calculated an incidence of anti-HMGCR IMNM using a large, multinational cohort. We highlight the refractory nature and long-term impacts of anti-HMGCR IMNM. We also describe the unique phenotype of statin-naïve anti-HMGCR IMNM, and the rare occurrence of self-limiting myopathy.