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Abstract Number: 1174

Anti-HMGCR Immune-mediated Necrotising Myopathy: Calculation of Incidence and Confirmation of Low Malignancy Risk in Two Independent Cohorts. a Retrospective Case Review

Thomas Khoo1, Xia Lyu2, James Lilleker1, Janine Lamb1, Vidya Limaye3 and Hector Chinoy4, 1University of Manchester, Manchester, United Kingdom, 2Department of Rheumatology, Shanghai Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China, 3Royal Adelaide Hospital, Adelaide, Australia, 4The University of Manchester, Sale, United Kingdom

Meeting: ACR Convergence 2023

Keywords: Epidemiology, Myopathies, Myositis

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Session Information

Date: Monday, November 13, 2023

Title: (1155–1182) Muscle Biology, Myositis & Myopathies – Basic & Clinical Science Poster II

Session Type: Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Immune-mediated necrotising myopathy (IMNM) is a rare complication of statin therapy, associated with the development of anti-HMGCR antibodies directed against the enzymatic target of statins (3-hydroxy-3-methylglutaryl-CoA). We sought to calculate the incidence of anti-HMGCR IMNM and determine whether there is a malignancy association in two independent cohorts of anti-HMGCR positive patients presenting to specialist rheumatology services in Greater Manchester (GM), United Kingdom, and South Australia (SA), Australia.

Methods: Patients with detected anti-HMGCR antibodies (January 2018-December 2022) were identified. Demographics, statin exposure, details of any previous or current malignancy, date of self-reported symptom onset and peak creatine kinase (CK) level were recorded. Using population data from 2021 by the Office of National Statistics (GM: 2.9 million people) and the Australian Bureau of Statistics (SA: 1.8 million people), annual incidences were calculated.

Results: The combined incidence of anti-HMGCR IMNM in our cohorts was 0.9-2.4 per million person years over the study period (Table 1). There was more than a doubling of incidence in GM from 2021 to 2022 despite stable testing practices (57-68 tests for anti-HMGCR performed annually). Twenty-four patients (50% female, 71% Caucasian, median age 63.6 years, range: 18.5-89.9 years) from GM and eight (37.5% female, 63% Caucasian, median age 70.3 years, range: 57.9-82.2 years) from SA were identified with a median follow-up of 16.3 months (range: 1.03-58.7 months). The time from first self-reported symptom to anti-HMGCR antibody testing was shorter in SA than GM (median 6.8 vs 22.5 months). Three patients (all female, aged 18, 28 and 60 years) were statin-naïve. Most patients (18/29) were exposed to atorvastatin (3/29 to simvastatin, 3/29 to rosuvastatin, 5/29 unknown). The median duration of statin use prior to anti-HMGCR testing was 36 months (range: 1-120 months). Five patients had a history of prior malignancy (hepatocellular, parotid, prostate (2), renal); notably all except one (data unavailable) occurred more than five years prior to anti-HMGCR testing. The median peak CK was 5000U/L (range: 964-39076U/L). Where data was available, CK subsequently normalised in 8/27 (29.6%) (time from treatment to stable normal CK: median 12 months, range: 2.3-69.2 months) and 8/25 (32%) had regained normal muscle power. Where data was available, more than half (10/16, 62.5%) remained on prednisolone at time of latest review (median 8 months after anti-HMGCR testing, median dose 5.5mg daily)

Conclusion: We confirm that anti-HMGCR is a rare subtype of inflammatory myopathy and report a recent apparent increase in the incidence of anti-HMGCR IMNM in the GM cohort. We found no temporal association of anti-HMGCR IMNM with malignancy within the timeframes usually defined for cancer-associated myositis. The difference between GM and SA in time from self-reported symptom onset to anti-HMGCR testing likely reflects varying pathways of specialist referral. Further multi-site collaborations will help to clarify the epidemiology of anti-HMGCR IMNM.

Supporting image 1

Table 1: Annual cases of anti-HMGCR myopathy and calculated incidence in Greater Manchester and South Australia


Disclosures: T. Khoo: None; X. Lyu: None; J. Lilleker: None; J. Lamb: Eli Lilly, 5; V. Limaye: None; H. Chinoy: AstraZeneca, 1, Biogen, 2, Eli Lilly, 5, GlaxoSmithKlein(GSK), 6, Novartis, 2, Orphazyme, 2, Pfizer, 1, UCB, 6.

To cite this abstract in AMA style:

Khoo T, Lyu X, Lilleker J, Lamb J, Limaye V, Chinoy H. Anti-HMGCR Immune-mediated Necrotising Myopathy: Calculation of Incidence and Confirmation of Low Malignancy Risk in Two Independent Cohorts. a Retrospective Case Review [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/anti-hmgcr-immune-mediated-necrotising-myopathy-calculation-of-incidence-and-confirmation-of-low-malignancy-risk-in-two-independent-cohorts-a-retrospective-case-review/. Accessed .
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