Antibody levels correlate with creatine kinase levels and strength in anti–3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase–associated autoimmune myopathy

Abstract

Objective: Autoantibodies recognizing 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) are found in patients with statin‐associated immune‐mediated necrotizing myopathy and, less commonly, in statin‐unexposed patients with autoimmune myopathy. The main objective of this study was to define the association of anti‐HMGCR antibody levels with disease activity. Methods: Anti‐HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti‐HMGCR–positive patients. Associations of antibody level with CK level and strength at visit 1 were analyzed in 55 patients, 40 of whom were exposed to statins. In 12 statin‐exposed and 5 statin‐unexposed patients with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated. Results: Antibody levels were associated with CK levels (P < 0.001), arm strength (P < 0.05), and leg strength (P < 0.05) at visit 1, but these associations were only significant among statin‐exposed patients in stratified analyses. With immunosuppressive treatment over 26.2 ± 12.6 months (mean ± SD), antibody levels declined (P < 0.05) and arm abduction strength improved (P < 0.05) in the 17 patients followed up longitudinally. The separate analysis showed that statin‐exposed patients developed decreased antibody levels (P < 0.01), decreased CK levels (P < 0.001), improved arm strength (P < 0.05), and improved hip flexion strength (P < 0.05) with treatment. Anti‐HMGCR antibody levels did not normalize in any patient. Conclusion: In the entire cohort, initial anti‐HMGCR levels correlated with indicators of disease activity; with immunosuppressive treatment, antibody levels declined and arm strength improved. Statin‐exposed patients had significant improvements in CK levels and strength whereas statin‐unexposed patients did not, suggesting a phenotypic difference between statin‐exposed and statin‐unexposed anti‐HMGCR–positive patients.