Immune-Mediated Necrotizing Myopathy: A Systematic Review of Antibody-Specific Mechanisms and Treatment Outcomes

Immune-mediated necrotizing myopathy (IMNM) is a rare, antibody-defined subset of idiopathic inflammatory myopathies characterized by rapidly progressive proximal muscle weakness, markedly elevated creatine kinase (CK) levels, and myofiber necrosis with minimal lymphocytic infiltration. Two major autoantibody subtypes-anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) and anti-signal recognition particle (anti-SRP)-define distinct clinical phenotypes, pathophysiologic mechanisms, and treatment responses. Despite growing recognition, optimal management strategies remain uncertain. Following PRISMA 2020 and MOOSE guidelines, PubMed, Scopus, Web of Science, and Embase were systematically searched for studies published between January 2011 and May 2025 using terms related to "immune-mediated necrotizing myopathy," "anti-HMGCR," and "anti-SRP". Eligible publications included biopsy-confirmed IMNM cases with antibody documentation and treatment or outcome data. Data extraction encompassed clinical features, immunopathology, therapeutic interventions, and relapse rates. Methodological quality was evaluated using the Joanna Briggs Institute (JBI) Checklist, NIH Quality Assessment Tool, Newcastle-Ottawa Scale (NOS), and ROBINS-I, depending on study design. Eighty-eight studies (n ≈ 230 patients) met the inclusion criteria. Anti-HMGCR IMNM typically affected middle-aged adults and was frequently associated with statin exposure, while anti-SRP IMNM presented at younger ages with more severe and treatment-refractory disease. Corticosteroids and IVIG were the most commonly used first-line agents, with additional benefit from steroid-sparing immunosuppressants (mycophenolate, azathioprine, methotrexate). Rituximab and other B-cell-targeted biologics achieved remission in approximately 60-70% of refractory cases, and emerging complement or FcRn-directed therapies showed early promise. Relapse occurred in 25-35% of cases, most often after tapering corticosteroids or immunosuppressants. Overall methodological quality was moderate to high, with 82% of studies meeting ≥75% of appraisal criteria across risk-of-bias domains. IMNM demonstrates antibody-specific differences in clinical course, therapeutic response, and prognosis. Early, aggressive, and combination immunotherapy improves outcomes, while novel biologic agents may benefit refractory disease. The overall certainty of evidence is moderate, supporting current management strategies yet underscoring the need for standardized diagnostic criteria and prospective multicenter studies to refine treatment algorithms and identify biomarkers of durable remission.