Biologic predictors of clinical improvement in rituximab-treated refractory myositis

BMC Musculoskelet Disord. 2015 Sep 17;16:257. doi: 10.1186/s12891-015-0710-3.

Abstract

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use*
  • Autoantibodies / blood
  • Biomarkers / blood
  • Chemokines / blood
  • Cytokines / blood
  • Dermatomyositis / blood
  • Dermatomyositis / diagnosis
  • Dermatomyositis / drug therapy*
  • Dermatomyositis / immunology
  • Double-Blind Method
  • Humans
  • Polymyositis / blood
  • Polymyositis / diagnosis
  • Polymyositis / drug therapy*
  • Polymyositis / immunology
  • Remission Induction
  • Rituximab / therapeutic use*
  • Severity of Illness Index
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Time Factors
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Autoantibodies
  • Biomarkers
  • Chemokines
  • Cytokines
  • Rituximab