P152 The incidence of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies may be higher than we think
Authors: Joseph Vikram M K , Rose Emily C , Lloyd Mark , Edwards Christopher J , Amar Soha K , Forster Tamara , Smith Karen A , Wheeler Rachel D , Kiely Patrick D W 
Published: April 2021

Background/Aims 

Statins are associated with muscle symptoms, from myalgia with normal CK, to rhabdomyolysis. A sub-group have an autoimmune necrotising myopathy with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies. This can present variably, from mild self-limiting illness to severe myopathy unresponsive to statin withdrawal, requiring long-term immunosuppression. A study from New Zealand estimated the incidence of anti-HMGCR-associated myositis to be 1 in 90,000 statin users, and an incidence of 1 in 500,000 has been estimated in a US population. Anti-HMGCR antibodies were first reported in 2010. As they are new, and testing is not widely available, they may be under-recognised in the routine assessment of patients with myopathies. However, detection is important as prompt immunosuppression may be needed.

Methods 

We compared the 2019 incidence of anti-HMGCR antibodies in Southern England from two different laboratory groups, utilising different testing criteria. The St George’s and Berkshire Surrey Pathology Services (StG/BSPS) laboratories serve a population of 3.25 million and test anti-HMGCR antibodies solely on clinician request. The Southampton laboratory serves a population of 2.33 million and tests anti-HMGCR as part of the immunoblot for all myositis-associated antibodies and where clinical details suggest myositis or ILD.

Results 

In 2019, 14 tests were performed by StG/BSPS and 662 by Southampton, with anti-HMGCR positives of 5 (36%) and 28 (4.2%) respectively. Adjusted to include only the adult population, the incidence of anti-HMGCR antibodies is 1 in 514,000 in the StG/BSPS area versus 1 in 66,000 in the Southampton area. We estimate statins to be used in 308,000 adults in the StG/BSPS and in 220,000 in the Southampton areas, assuming treatment in 12% of adults and age demographics representative of the national population. This suggests an incidence of anti-HMGCR antibodies of approximately 1 in 62,000 statin users in the StG/BSPS area and 1 in 8,000 statin users in the Southampton area, though statin exposure was not confirmed in all positive cases.

Preliminary data from 17 anti-HMGCR positive cases shows that 76% had taken statins, for an average duration of 5.84 years (range 0.75-16 years). Median peak CK was 6489 (range 241-27555). 76% required immunosuppression, of which 70% required two or more different treatments.

Conclusion 

The 7.7-fold higher incidence from the Southampton laboratory reflects a proactive approach, selecting far more samples for anti-HMGCR assessment than specifically requested by clinicians. This demonstrates under-awareness of this antibody in routine care. We propose adoption of an algorithm to trigger more widespread testing for anti-HMGCR antibodies, to identify cases amongst those with statin-associated myalgia or myositis, and in others without statin exposure. This will lead to better understanding of the spectrum of clinical disease associated with anti-HMGCR antibodies, as well as early detection and treatment of those who develop a necrotising myopathy.

Disclosure 

V.M.K. Joseph: None. E.C. Rose: None. M. Lloyd: None. C.J. Edwards: None. S.K. Amar: None. T. Forster: None. K.A. Smith: None. R.D. Wheeler: None. P.D.W. Kiely: None.