Immune-mediated necrotizing myopathies: clinico-serological features and treatment outcomes of a large Italian cohort of patients

Background: Immune-mediated necrotizing myopathy (IMNM) is a distinct entity with limited large-cohort data. We aimed to characterize clinico-serological features and treatment outcomes of anti-SRP, anti-HMGCR, and seronegative IMNM in a large Italian cohort. Methods: Retrospective multicenter study of adults diagnosed with IMNM (224th ENMC criteria) across 14 Italian neuromuscular centers between 2019 and 2022 was performed. Results: We included 159 subjects (57% female, median age 62 years): 40 SRP+, 71 HMGCR+, 41 seronegative, and 7 untested. SRP+ more frequently presented with proximal upper limb weakness and axial involvement versus HMGCR+ (OR = 3.89, padj = 0.007, OR = 3.47, padj = 0.04) and seronegative (OR = 4.00, padj = 0.014, OR = 15.2, padj = 0.005). Lung involvement was higher in SRP+ (7.5%), vs none in HMGCR+ and 2.4% in seronegative (p=0.028). Extramuscular features were more frequent in HMGCR+ (OR = 3.78, p = 0.019, padj = 0.057). SRP+ had higher odds of loss of motor independence (OR=4.22, padj =0.011) and relapse (OR = 14.4, padj = 0.010) than HMGCR+. Seronegative had better functional outcomes than SRP+ (p=0.047). Cancer associated myositis predicted worse disability (OR = 6.93, p = 0.0044). Overall, 71.7% improved with corticosteroids (OR=3.83, padj =0.01) and immunosuppressants (OR=2.296, padj =0.037), without serotype differences. CK decreased in 81.8% and normalized in 40.3% of patients; ΔCK was associated with improvement (p=0.017), clinical remission (p=0.002) and correlated with post-treatment functional scores (R=0.19, p= 0.044). Conclusion: Subtype-specific differences and prognostic factors emerge. Exploratory functional assessment and ΔCK may capture treatment response in real-world settings.