A team of researchers from the Johns Hopkins Division Rheumatology and National Institutes of Health, led by Eleni Tiniakou, M.D., Iago Pinal-Fernandez, M.D., Ph.D., Lisa Christopher-Stine M.D., M.P.H., and Andrew L. Mammen, M.D., Ph.D., found that younger patients with anti-HMGCR associated myositis have more severe disease and a worse prognosis than older patients. This form of myositis, associated with antibodies to a protein called HMGCR, is a rare disease that requires long-term immunosuppression, but prior to this study little was known about how patients progressed in their disease over time or responded to treatment.
Why was this study done?
Anti-HMGCR associated autoimmune myositis is an exceptionally rare disease marked by severe muscle weakness that is thought to be caused by an over-active immune response directed against muscle. In most patients, development of this disease follows exposure to statins for the treatment of high cholesterol. Its incidence is not known with certainty, but is estimated to occur in approximately 2 to 3 out of every 100,000 patients treated with statins. In a prior analysis of 17 patients with anti-HMGCR-associated myositis, the authors showed that muscle strength improved with immunosuppressive treatment to inhibit the immune system. However, the small number of patients included in that study did not allow them to draw definitive conclusions about the natural course of the disease and the expected rate of recovery among patients. This new study was designed to follow patients over time to understand the clinical course of patients treated for anti-HMGCR associated myositis and identify important factors linked to the rate of recovery.
How was this study done?
The researchers enrolled 104 patients with anti-HMGCR associated myositis who were seen for their clinical care at the Johns Hopkins Myositis Centre and studied their disease for an average of 3 years. At each study visit, serum samples were screened for anti-HMGCR autoantibodies and creatine kinase (CK) level, a marker of muscle damage. Muscle strength was also evaluated by the examining physician.
What were the major findings?
The authors were surprised to find that younger age predicted more severe disease. Younger patients had more severe weakness at the first visit compared with their older counterparts. Furthermore, older patients had a faster rate of strength improvement compared to younger patients. While 85% of patients over 60 years old reached nearly normal muscle strength within 4 years after disease diagnosis, only 45% of patients under age 50 recovered full strength. This pattern was observed, even among patients who were not previously exposed to statins, suggesting that even though statins are associated with developing the disease, they do not predict the severity or outcome of the disease.
Among those patients who were treated with drugs that suppress the immune system, a significant number regained normal strength. However, the majority continued to have elevated CK levels, indicating continued muscle damage, even in the setting of normal strength. All but 3 out of 105 patients were treated with immunosuppressive treatment, but only a handful could be weaned off therapy without having worsening of disease. Importantly, the authors found that nearly 1/3 of patients with anti-HMGCR associated myositis had disease that continued to worsen, despite aggressive treatment with immunosuppressive therapy, and these patients tended to be younger.
What is the impact of this work?
Since anti-HMGCR associated myositis is a relatively newly described disease, little was known about the natural disease course, factors that influence disease course or response to treatment, and what it means to have elevated CK levels with normal muscle strength. This study has shed light on these aspects of this disease and can guide patients and doctors in the way they think about treatment. Most importantly, this work suggests that physicians should consider more aggressive treatment for younger patients, who tend to have worse disease outcomes. It will be important to understand why age affects the disease outcome and what is causing the disease in people who have not been exposed to statins.
News or Publication Link
More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Tiniakou E, Pinal-Fernandez I, Lloyd TE, Albayda J, Paik J, Werner JL, Parks CA, Casciola-Rosen L, Christopher-Stine L, Mammen AL. Rheumatology (Oxford). 2017 Jan 17.