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- Title
Biologic predictors of clinical improvement in rituximab-treated refractory myositis.
- Authors
Reed, Ann M.; Crowson, Cynthia S.; Hein, Molly; Lopez de Padilla, Consuelo; Olazagasti, Jeannette M.; Aggarwal, Rohit; Ascherman, Dana P.; Levesque, Marc C.; Oddis, Chester V.; de Padilla, Consuelo Lopez; RIM Study Group
- Abstract
<bold>Background: </bold>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. <bold>Methods: </bold>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. <bold>Results: </bold>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 < 0.001). At 16 weeks after rituximab, anti-synthetase and Mi-2 autoAb positive subjects and non-MAA had a greater improvement in IFNCK scores (- 6.7, - 6.1 and -7.2, p < .001). Both IFNCK high scores (>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). <bold>Conclusion: </bold>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.
- Subjects
RITUXIMAB; AUTOANTIBODIES; CHEMOKINES; CYTOKINES; FORECASTING; MYOSITIS; RESEARCH funding; STATISTICAL sampling; T cells; TIME; RANDOMIZED controlled trials; TREATMENT effectiveness; DISEASE remission; BLIND experiment; SEVERITY of illness index
- Publication
BMC Musculoskeletal Disorders, 2015, Vol 16, Issue 1, p1
- ISSN
1471-2474
- Publication type
journal article
- DOI
10.1186/s12891-015-0710-3