Targeted Therapy for Idiopathic Inflammatory Myopathy

Abstract

Background: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune disorders characterized by chronic muscle inflammation and significant extramuscular involvement. A substantial proportion of patients exhibit refractory or relapsing disease despite conventional immunosuppressive therapies, necessitating the development of novel targeted treatments. Recent immunological advances have identified novel therapeutic targets-including B cells, T cells, cytokines and intracellular signalling pathways-paving the way for personalized treatment. Targeted therapies represent promising new approaches.

Methods: This comprehensive review synthesizes current evidence on targeted therapies for IIM. We systematically searched PubMed, the Cochrane Library and Google Scholar for studies published before September 2025, including randomized controlled trials, retrospective and observational studies, meta-analyses and case reports. We synthesized evidence on the efficacy and safety of various targeted treatments across IIM subtypes and complications, highlighting recent advances and future directions.

Results: Targeted therapies are revolutionizing IIM management. B-cell-targeted therapies constitute a relatively established modality. Rituximab has become a cornerstone therapy for refractory disease, as supported by high-level evidence. Modulation of T-cell costimulation with abatacept benefits specific subtypes. JAK inhibitors show remarkable efficacy, particularly for cutaneous manifestations and interstitial lung disease. Cytokine inhibitors, proteasome inhibitors and low-dose IL-2 also show benefits across various IIM subtypes and complications. Novel mechanisms are emerging, including Fc receptor antagonism (efgartigimod) to reduce pathogenic IgG and advanced cellular therapies such as CAR-T-cell therapy and bispecific T-cell engagers (BiTEs), which have induced sustained remission in severe refractory cases. The heterogeneous treatment responses observed between and within IIM subtypes present a central challenge, largely stemming from their diverse underlying immunopathogenic mechanisms. The primary safety concern remains infection risk, necessitating individualized benefit-risk assessment.

Conclusion: The targeted therapy landscape in IIM is rapidly expanding, enabling more precise and effective management. These strategies show significant promise in improving outcomes for patients with refractory disease. Future efforts should focus on optimizing treatment selection through biomarker discovery, conducting larger randomized trials to strengthen the evidence base, and managing long-term safety.

Keywords: CAR‐T; biological products; idiopathic inflammatory myopathies; immunotherapy; molecular targeted therapy; myositis.

FIGURE 1

The targeted therapy mechanism map of idiopathic inflammatory myopathy.