Background/Purpose: While the majority of myopathy patients with antibodies recognizing H 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) have had a statin exposure, approximately one third have not.  In a previous study, we reported on the evolution of antibody titers, muscle strength, and creatine kinase (CK) levels of 17 anti-HMGCR+ subjects with and without statin exposure followed longitudinally between May 2002 and July 2011.  We found that (a) antibody titers correlated with CK and muscle weakness and (b) only statin-exposed patients clearly improved with immunosuppressive therapy.  Here, we extend that study to these and additional anti-HMGCR+ patients followed for an additional 4 years. 

Methods: Anti-HMGCR titers, CK levels, muscle strength and immunosuppressive treatment for each visit were assessed for 117 anti-HMGCR patients of the Johns Hopkins Myositis Cohort. Twenty-six patients were followed longitudinally with more than 4 visits, of which 7 were statin-unexposed. 

Results: We confirmed our previous finding that statin-exposed patients experience improved strength, decreased CK levels, and decreased antibody titers with immunosuppressive therapy.  Here, we demonstrate for the first time that statin-unexposed patients, despite a decrease in both anti-HMGCR titers and CK levels with immunosuppressive therapy, still have a steady decline in proximal muscle strength (deltoid, p<0.001 and hips, p=0.001) over time.

Conclusion: Unlike statin-exposed anti-HMGCR+ patients, who improve with immunosuppressive therapy, we found that statin-unexposed anti-HMGCR+  patients had a progressive decline in muscle strength despite aggressive treatement.  Interestingly, the decline in muscle strength occurred even though CK levels and antibody titers decreased over time.  These observations suggest that statin-exposed and statin-unexposed anti-HMGCR patients may have different underlying pathophysiological processes.  Statin-exposed patients seem to have a predominantly autoimmune disease that responds to therapy.  In contrast, we hypothesize that statin-unexposed patients have both an autoimmune process and an underlying myodegenerative process.  The autoimmune component can be at least partially treated with immunosuppressive therapy, explaining their decreasing CK levels and antibody titers.  However, we suspect that an underlying myodegenerative process does not respond to immunosuppression and causes progressive weakness.  Future studies will be aimed at determining whether statin-unexposed anti-HMGCR+ patients do, indeed, have an underlying myodegenerative process, such as a muscular dystrophy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-3-hydroxy-3-methylglutaryl-coenzyme-a-reductase-positive-myopathy-patients-without-statin-exposure-may-have-a-progressive-disease-that-worsens-despite-aggressive-immunosuppressive-therapy/