Biologic predictors of clinical improvement in rituximab-treated refractory myositis.

Published online

Journal Article

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 < 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). 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.

Full Text

Duke Authors

Cited Authors

  • Reed, AM; Crowson, CS; Hein, M; de Padilla, CL; Olazagasti, JM; Aggarwal, R; Ascherman, DP; Levesque, MC; Oddis, CV; RIM Study Group,

Published Date

  • September 17, 2015

Published In

Volume / Issue

  • 16 /

Start / End Page

  • 257 -

PubMed ID

  • 26382217

Pubmed Central ID

  • 26382217

Electronic International Standard Serial Number (EISSN)

  • 1471-2474

Digital Object Identifier (DOI)

  • 10.1186/s12891-015-0710-3

Language

  • eng

Conference Location

  • England