Management of Inflammatory Myositis: Options for Refractory Disease & New Therapies Discussed

Dr. Landon-Cardinal  discussed current investigations into targets and treatments in the pipeline for immune-mediated necrotizing myopathy (IMNM), inclusion-body myositis (IBM) and myositis-associated interstitial lung disease. Of these, she described the first trial looking at a complement inhibitor (zilucoplan) to treat IMNM, as well as published data from two randomized trials assessing the efficacy of targeted therapies for IBM.^5,6

Results of a trial assessing the efficacy and safety of sirolimus, an mTOR pathway inhibitor, for IBM found that sirolimus conferred no difference in quadriceps strength—the study’s primary end point—at 52 weeks, but was associated with a significant difference in six-minute walk distance, forced vital capacity, Health Assessment Questionnaire–Disability Index (HAQ-DI) and thigh fat fraction—secondary end points. Dr. Landon-Cardinal noted the evidence in these positive end points supports further investigation with another randomized trial. She also noted that 45% of patients treated with sirolimus experienced serious adverse events, such as mouth ulcers, aseptic pneumonia and lower limb edema.⁵

Dr. Landon-Cardinal also discussed a long-term extension study on the use of bimagrumab, a myostatin inhibitor, for IBM that showed a good safety profile with only rare serious events but no difference from placebo in efficacy (i.e., six-minute walk distance), which resulted in ending the study early.⁶

Along with a planned phase 3 trial of sirolimus, other agents in the pipeline to treat IBM include arimoclomol, an inducer of the heat shock protein response, and ABC008, an anti-KLRG1 antibody.

References

1. Lundberg IE. Expert perspective: Management of refractory inflammatory myopathy. Arthritis Rheumatol. 2021 Aug;73(8):1394–1407.
2. Oddis CV, Aggarwal R. Treatment in myositis. Nat Rev Rheumatol. 2018 May;14(5):279–289.
3. Paik JJ, Casciola-Rosen L, Shin JY, et al. Study of tofacitinib in refractory dermatomyositis: An open-label pilot study of ten patients. Arthritis Rheumatol.2021 May;73(5):858–865.
4. Kim YJ, Schiopu E, Dankó K, et al. A phase 2, double-blinded, placebo-controlled trial of toll-like receptor 7/8/9 antagonist, IMO-8400, in dermatomyositis. J Am Acad Dermatol.2021;84(4):1160–1162.
5. Benveniste O, Hogrel JY, Belin L, et al. Sirolimus for treatment of patients with inclusion body myositis: A randomized, double-blind, placebo-controlled, proof-of-concept, phase 2b trial. Lancet Rheumatol. 2021;3(1):e340–e348.
6. Amato AA, Hanna MG, Machado PM, et al. Efficacy and safety of bimagrumab in sporadic inclusion body myositis: Long-term extension of RESILIENT. 2021 Mar 23;96(12):e1595–e1607.