Biologic predictors of clinical improvement in rituximab-treated refractory myositis Clinical rheumatology and osteoporosis

Background: To examine the longitudinal utility of a biomarker signature in conjunction with myositis autoantibodies (autoAbs) as predictors of disease improvement in refractory myositis patients treated with rituximab. Methods: In the RIM Trial, all subjects received rituximab on 2 consecutive weeks. Using start of treatment as baseline, serum samples (n∈=∈177) were analyzed at baseline and after rituximab with multiplexed sandwich immunoassays to quantify type-1 IFN-regulated and other pro-inflammatory chemokines and cytokines. Biomarker scores were generated for the following pathways: type-1 IFN-inducible (IFNCK), innate, Th1, Th2, Th17 and regulatory cytokines. Myositis autoAbs (anti-synthetase n∈=∈28, TIF-γ n∈=∈19, Mi-2 n∈=∈25, SRP n∈=∈21, MJ n∈=∈18, non-MAA n∈=∈24, unidentified autoantibody n∈=∈9, and no autoantibodies n∈=∈33) determined by immunoprecipitation at baseline, were correlated with outcome measures. Kruskal-Wallis rank sum tests were used for comparisons. Results: The mean (SD) values for muscle disease and physician global disease activity VAS scores (0-100 mm) were 46 (22) and 49 (19). IFNCK scores (median values) were higher at baseline in subjects with anti-synthetase (43), TIF1-γ (31) and Mi-2 (30) compared with other autoAb groups (p∈30) and autoAb group (Mi-2, non-MAA, and undefined autoantibody) demonstrated the greatest clinical improvement based on muscle VAS (muscle-interaction p∈=∈0.075). Conclusion: Biomarker signatures in conjunction with autoAbs help predict response to rituximab in refractory myositis. Biomarker and clinical responses are greatest at 16 weeks after rituximab

Update on outcome assessment in myositis

The adult and juvenile myositis syndromes, commonly referred to collectively as idiopathic inflammatory myopathies (IIMs), are systemic autoimmune diseases with the hallmarks of muscle weakness and inflammation. Validated, well-standardized measures to assess disease activity, known as core set measures, were developed by international networks of myositis researchers for use in clinical trials. Composite response criteria using weighted changes in the core set measures of disease activity were developed and validated for adult and juvenile patients with dermatomyositis and adult patients with polymyositis, with different thresholds for minimal, moderate and major improvement in adults and juveniles. Additional measures of muscle strength and function are being validated to improve content validity and sensitivity to change. A health-related quality of life measure, which incorporates patient input, is being developed for adult patients with IIM. Disease state criteria, including criteria for inactive disease and remission, are being used as secondary end points in clinical trials. MRI of muscle and immunological biomarkers are promising approaches to discriminate between disease activity and damage and might provide much-needed objective outcome measures. These advances in the assessment of outcomes for myositis treatment, along with collaborations between international networks, should facilitate further development of new therapies for patients with IIM