OBJECTIVE: No clinical trials have been conducted to establish optimal and effective treatment in patients with immune-mediated necrotizing myopathy (IMNM), which can have a refractory course with increased morbidity from permanent muscle damage, especially in patients who experience delay in diagnosis and treatment. A subset of autoimmune necrotizing myopathy is associated with antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Treatment involves withdrawing statins and using a combination of immunosuppressant and immunomodulatory treatment. Our study aims to provide longitudinally collected data on outcomes of early versus late initiation of intravenous Ig (IVIG) using our myositis center cohort of patients with anti-HMGCR IMNM.
METHODS: We conducted a retrospective chart review of 31 adult patients of the Oregon Health and Science University Myositis Center who were diagnosed with anti-HMGCR IMNM from September 2016 through October 2022 and reviewed physical examination, serologic laboratory data, and their treatment including prednisone reception as well as treatment response at 0 (the evaluation immediately before IVIG initiation), 3, 6, and 12 months on treatment. We divided this cohort into those who received IVIG at or before six months after receiving the diagnosis of anti-HMGCR IMNM and refer this as the cohort with nondelayed treatment, and those who received IVIG after six months following their diagnosis, which we referred to as the cohort with delayed treatment. Diagnosis of anti-HMGCR IMNM was defined as per the 2016 European Neuromuscular Centre criteria as having all three of elevated serum creatine kinase (CK), proximal muscle weakness, and anti-HMGCR antibodies. We evaluated the response to treatment by using a limited total improvement score (TIS) as per 2016 American College of Rheumatology/EULAR myositis response criteria.
RESULTS: Among the 31 total patients, 19 were included within the cohort with nondelayed treatment, and 12 within the cohort with delayed treatment. The two cohorts had a comparable amount of time between the onset of symptoms and diagnosis; however, the cohort with delayed treatment had a significantly longer time between diagnosis and IVIG treatment (P < 0.001). At disease onset, cohorts had a comparable serum CK (P > 0.999), but patients with delayed treatment had an expected lower serum CK (P = 0.016) at the 0-month time point. At the 0-month time point, nine of the patients with nondelayed treatment (47%) required the use of a walker or wheelchair, whereas eight of the cohort with delayed treatment (66%) did. Patients who received nondelayed treatment demonstrated significant improvement in manual muscle testing 8 at the 12-month intervals (P < 0.001). Average serum CK values of all patients measured at the 3, 6, and 12 months did not significantly differ between the groups with nondelayed and delayed treatment. TIS improved more in the group with nondelayed treatment than in the group with delayed treatment (P = 0.002 at 3 months, P = 0.019 at 6 months, and P = 0.001 at 12 months). Seven patients in the group with delayed treatment had permanent residual muscle weakness requiring walker or wheelchair use at 12 months, whereas none of the patients in the group with nondelayed treatment did.
CONCLUSION: Though our results have limitations, they contribute to a growing body of evidence that suggests that IVIG may prove to be a valuable addition to an early and aggressive induction regimen in patients afflicted by anti-HMGCRIMNM, particularly those with moderate to severe weakness requiring the use of a wheelchair or walking aids. Delay in IVIG treatment may lead to the development of permanent residual weakness and long-term disability.