Immune-mediated necrotizing myopathy (IMNM) is a type of autoimmune myopathy associated with severe proximal muscle weakness, increased muscle enzyme concentrations, and myofiber necrosis with rare inflammatory cell infiltrates. Patients with IMNM may develop disabling muscle weakness if their first line of therapy does not work effectively. As autoantibodies might be responsible for muscle damage in IMNM through activation of the complement system, this clinical study investigated the safety, efficacy, and tolerability of the candidate drug zilucoplan, a C5 complement inhibitor, in patients with IMNM.

What is exciting about this article?

In this randomized clinical trial, the researchers evaluated IMNM clinical symptoms after 8 weeks of zilucoplan therapy. They showed that zilucoplan treatment did not improve IMNM symptoms. Nevertheless, this study helped establish that complement inhibition is not an effective treatment for people with IMNM and that complement activation is unlikely to be the primary driver of muscle damage in this disease. As such, this study serves as a starting point for future studies on IMNM. The results of this study provided valuable insight into the pathophysiology of IMNM and, as the first clinical trial for the disease, helped ensure that future efforts could be more efficient.

How does this fit into the larger NIAMS portfolio?

Dr. Mammen’s research focuses on the diagnosis and treatment of human muscle diseases. This study was the first randomized clinical trial for IMNM and evaluated the safety, efficacy, and tolerability of zilucoplan therapy.

Grant support


Research Areas:

Clinical Research Immunology Muscle Biology


Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial.

Mammen AL, Amato AA, Dimachkie MM, Chinoy H, Hussain Y, Lilleker JB, Pinal-Fernandez I, Allenbach Y, Boroojerdi B, Vanderkelen M, Delicha EM, Koendgen H, Farzaneh-Far R, Duda PW, Sayegh C, Benveniste O
Lancet Rheumatol.
2023 Feb;
doi: 10.1016/s2665-9913(23)00003-6
PMID: 36923454

Research reported in this publication was supported by the Intramural Research Program of the NIHʼs National Institute of Arthritis and Musculoskeletal and Skin Diseases.