The incidence of anti-HMGCR immune-mediated necrotizing myopathy: an Australian and UK retrospective multi-site cohort study
Publication Details
Khoo, T.,
Tan, E.,
Gunawardena, H.,
Sadler, R.,
Lamb, J.,
Lyu, X.,
Brusch, A.,
Needham, M.,
Austin, K.,
Bahadori, A.,
Buch, M.,
Tomaszewski, M.,
Lilleker, J.,
&
Chinoy, H.
(2025).
The incidence of anti-HMGCR immune-mediated necrotizing myopathy: an Australian and UK retrospective multi-site cohort study.
Rheumatology, 64 (9), 4995-5003.
Abstract
Objectives
Immune-mediated necrotizing 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
One hundred and nine 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/year. One hundred and one patients were statin-exposed, mostly atorvastatin (77/101, 76.2%). Median statin duration before 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 7020 IU/l (range: 964–39076), and 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 of anti-HMGCR IMNM. We also describe the unique phenotype of statin-naïve anti-HMGCR IMNM, and the rare occurrence of self-limiting myopathy.
Keywords
myositis, statins, myopathy, immune-mediated necrotizing myopathy
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