Benefits of Early vs Late Initiation of IVIG in the Treatment of Anti-HMGCR Immune-Mediated Necrotizing Myopathy.

BACKGROUND/OBJECTIVE: No clinical trials have been conducted to establish optimal and effective treatment in Immune-Mediated Necrotizing Myopathy (IMNM), which can have a refractory course with increased morbidity from permanent muscle damage especially in cases with 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 immunoglobulin (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 & Science University (OHSU) Myositis Center who were diagnosed with anti HMGCR-IMNM from September 2016 through October 2022 and reviewed physical exam, serologic lab data and their treatment including prednisone use as well as treatment response at the 0-months (the evaluation immediately prior to IVIG initiation), 3-months, 6-months and 12-months on treatment. We divided this cohort into those who received IVIG at or prior to 6 months after receiving the diagnosis of Anti-HMGCR IMNM and refer this as the "Non-Delayed" cohort, and those who received IVIG after 6 months following their diagnosis, which we referred to as "Delayed" cohort. Diagnosis of Anti-HMGCR IMNM was defined as per the 2016 ENMC criteria as having all 3 of: elevated serum 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 ACR/EULAR myositis response criteria.

RESULTS: Amongst the 31 total patients, 19 were included within the Non-Delayed cohort, and 12 within the Delayed cohort. The two cohorts had a comparable amount of time between onset of symptoms and diagnosis; however, the Delayed cohort had a significantly longer time between diagnosis and IVIG treatment (p-value <0.001). At disease onset, cohorts had a comparable serum CK (p-value >0.999), but Delayed patients had an expected lower serum CK (p-value 0.016) at the 0-month time point. At the 0-month time point, 9 (47%) of the Non-Delayed patients required the use of a walker or wheelchair, while 8 (66%) of the Delayed cohort did. Non-Delayed patients demonstrated significant improvement in MMT8 at the 12-months intervals (p-value <0.001). Average serum CK values of all patients measured at the 3-month, 6-month, and 12-month did not significantly differ between the Non-Delayed and Delayed group. TIS improved more in the Non-Delayed group than in the Delayed group (p-value 0.002 at 3-months, 0.019 at 6-months and 0.001 at 12-months). Seven patients in the delayed group had permanent residual muscle weakness requiring walker or wheelchair use at 12-months while none of the patients in the Non-Delayed group did.

CONCLUSION: Though our results have limitations, they contribute to a growing body of evidence which suggests that IVIG may prove to be a valuable addition to an early and aggressive induction regimen in patients afflicted by anti HMGCR IMNM. Delayed in IVIG treatment may lead to the development of permanent residual weakness and long-term disability.