The Efficacy of Tocilizumab in the Treatment of Patients with Refractory Immune-Mediated Necrotizing Myopathies: An Open-Label Pilot Study

• Main Authors: Sizhao Li (Author), Wenli Li (Author), Wei Jiang (Author), Linrong He (Author), Qinglin Peng (Author), Guochun Wang (Author), Xin Lu (Author)
• Format: Book
• Published: Frontiers Media S.A., 2021-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1663-9812; 10.3389/fphar.2021.635654
• Keywords: immune-mediated necrotizing myopathy; tocilizumab; treatment; biomarker; interleukin-6; Therapeutics. Pharmacology; RM1-950
• Source: Frontiers in Pharmacology, Vol 12 (2021)

Objective: To evaluate the efficacy of tocilizumab (TCZ) in adult patients with refractory immune-mediated necrotizing myopathies (IMNMs) and investigate possible predictive biomarkers of the response to treatment with TCZ.Methods: Patients with refractory IMNM were enrolled in this open-label pilot observational study and received intravenous TCZ treatment. The clinical response was assessed after 6 months of TCZ treatment according to the 2016 American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) response criteria for adult dermatomyositis and polymyositis. Muscle biopsies were performed to investigate muscle fiber regeneration by immunohistochemical staining of CD56. Serum levels of interleukin (IL)-6 were measured using a multiplex bead-based flow fluorescent immunoassay. The levels of muscle IL-6 mRNA were detected by real-time polymerase chain reaction.Results: A total of 11 patients with refractory IMNM were enrolled in the study, including 3 anti-3-hydroxy-3-methylglutaryl-CoA reductase- and 8 anti-signal recognition particle-positive patients. Seven (63.6%) of these patients achieved clinically significant responses according to the 2016 ACR-EULAR myositis response criteria. Responders had higher baseline serum IL-6 and muscle IL-6 mRNA levels and percentage of CD56-positive muscle fibers than non-responders. Baseline serum IL-6 levels and the percentage of CD56-positive muscle fibers were positively correlated with total improvement score after 6 months of TCZ treatment. Furthermore, muscle fiber necrosis and muscle fiber size variation decreased in repeated muscle biopsies in five responders.Conclusion: Patients with refractory IMNM may respond to TCZ. Baseline serum IL-6 and muscle IL-6 mRNA levels and the percentage of CD56-positive muscle fibers may predict the response to TCZ treatment in these patients.