Year: 2017
Type: article
Abstract: In addition to the above, in 2010 an immune-mediated necrotizing myositis with autoantibodies against HMGCR was first described.3 This condition is now well recognized with numerous studies highlighting its association with statin usage.3-5 Unlike the common self-limiting statin myopathies which may be seen in up to 10% of statin users, anti-HMGCR-associated myositis remains a rare condition with an estimated yearly incidence of 1/90 000 statin users and 1/1 700 000 statin-naïve patients.5 The lack of response to statin withdrawal and the presence of a specific autoantibody suggests an autoimmune, rather than a toxic pathology. As anti-HMGCR autoantibodies are felt to be specific for an immune-mediated necrotizing myositis, one would not expect to identify them in patients with a self-limiting statin myopathy. This study sought to confirm this hypothesis. The anti-HMGCR enzyme-linked immunosorbent assay (ELISA) has been shown to be a highly sensitive and specific test for identifying anti-HMGCR autoantibodies.6, 7 As previously reported, an anti-HMGCR ELISA was developed at Canterbury Health Laboratories in early 2014.5 This assay has been validated against the INOVA QUANTA lite assay and been used to report 10 patients with HMGCR-associated myositis.5 Using this assay we tested for the presence of anti-HMGCR autoantibodies in 79 patients with a history of statin-induced myalgia. Forty-two patients were participants in a double-blinded trial of co-enzyme Q10 supplementation8 while a further 37 were known to the Lipid Disorders and Cardiovascular Prevention clinic. All patients had been unable to tolerate adequate doses of statin therapy due to muscle discomfort or weakness. The patients known to the Lipid Disorders and Cardiovascular Prevention clinic had muscle symptoms that resolved when statin therapy was discontinued but reoccurred on statin re-challenge. While not all patients were symptomatic at the time of testing, it is known that anti-HMGCR autoantibodies are persistent even in those who have been treated and achieved disease remission.9 Forty-four patients were female and 35 male. The mean age was 61.1 years (range 22–78). The mean CK was 128 U/L with no patients having a CK greater than three times the upper limit of normal. Simvastatin was the most commonly implicated statin. No patients tested positive for anti-HMGCR autoantibodies via ELISA. The prevalence of anti-HMGCR autoantibodies in this population with self-limiting statin myopathy was therefore 0% (95% CI 0–4.5%). Myalgia is a common complaint among statin users. While most cases are mild and resolve on drug cessation, it is now recognized that an immune-mediated necrotizing myositis with autoantibodies against HMGCR, the enzymatic target of statins, can occur. This condition tends to have an aggressive phenotype with significant myonecrosis and elevated CK levels. Unlike other immune-mediated myopathies, there are few reports of extra-muscular involvement. A recent paper has shown an association with malignancy although this has not yet been replicated in other reports.10 Identifying the subset of patients with immune-mediated myositis is important given the need to administer immunosuppressive treatment to control their disease. This study confirms that anti-HMGCR autoantibodies are not seen in patients with self-limiting statin myopathy. This is in keeping with two previous studies which have also looked at this question. In a large population of statin users, including 51 statin intolerant patients, Mammen et al. showed a low rate of anti-HMGCR positivity.6 A recent study of 101 patients who developed self-limiting statin-related myopathy while on cerivastatin, did not reveal any patients with anti-HMGCR autoantibodies.11 Taken together this suggests that there is no value in testing for anti-HMGCR autoantibodies in patients with statin intolerance or self-limiting statin myopathy. As the anti-HMGCR ELISA has a reported false positive rate of 0.7%, testing such patients could potentially lead to patient misclassification and inappropriate treatment being given.12 This highlights the importance of testing only patients with a high pre-test probability of having an immune-mediated myositis. It has been suggested that anti-HMGCR autoantibodies should only be tested in patients with a CK >10 times the upper range of normal who do not respond to statin cessation.12 This suggestion is based on results from a number of case series where all patients had CK levels above this cutoff.3, 5 This paper has a number of limitations that need to be recognized. The study is retrospective in nature with a relatively small number of patients. Other known myositis autoantibodies were not tested and muscle biopsies were not performed. While it is conceivable that a statin-associated autoimmune myopathy could exist in the absence of anti-HMGCR autoantibodies, there are currently no reports of this occurring. This study has confirmed that anti-HMGCR autoantibodies are not seen in patients who are intolerant of statins due to self-limiting muscle symptoms. Given this, we would suggest that there is no value in testing such patients for the presence of anti-HMGCR autoantibodies. We are grateful to Inova diagnostics for providing a test kit to confirm a reference serum for our in-house ELISA.
Authors: Paula Keating, Joanna Young, Peter George, Chris Florkowski, Myfanwy Spellerberg, Nicholas Kennedy
Institutions: Christchurch Hospital, Canterbury Health Laboratories
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2587366334