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Werner, Cassie A. To study disease severity and response to therapy in a large cohort of patients with anti-hydroxymethylglutaryl-coenzyme A reductase HMGCR -associated myositis. Muscle strength, creatine kinase levels and treatments were assessed in anti-HMGCR-positive patients at each clinical visit. Univariate and multivariate analyses were used to analyse the influence of clinical characteristics on strength and the change in strength over time.
Whole exome sequencing was performed in a subset of patients. Among eight refractory patients with DNA available for testing, whole exome sequencing did not reveal pathogenic mutations in known dystrophy genes. The risk of cancer was not increased in anti-HMGCR myositis patients compared with the general population. Although younger patients had more severe disease and a worse prognosis than older patients, they did not have evidence of a known co-existing muscular dystrophy to explain their persistent, and sometimes progressive, muscle weakness.
Anti-hydroxymethylglutaryl-coenzyme A reductase myositis is usually a chronic disease requiring long-term immunosuppression. Younger anti-hydroxymethylglutaryl-coenzyme A reductase myositis patients have more severe disease and a worse prognosis than older patients. Anti-hydroxymethylglutaryl-coenzyme A reductase myositis patients did not have an increased risk of cancer.
Autoantibodies recognizing hydroxymethylglutaryl-coenzyme A reductase HMGCR are specifically found in patients with autoimmune myopathy and are strongly associated with both a necrotizing myopathy on biopsy and a history of statin exposure [ 1—4 ]. However, the relatively small number of patients included in that study did not allow us to draw definitive conclusions about the expected rate of recovery or patient characteristics that influence long-term outcomes.
In the current study, we have analysed longitudinal CK levels, muscle strength, autoantibody titres and treatments in a much larger cohort of anti-HMGCR myositis patients. All patients evaluated at the Johns Hopkins Myositis Centre with suspected myopathy were enrolled in a longitudinal study. Serial strength measurements for each patient were made by the same physician.