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Biologic predictors of clinical improvement in rituximab-treated refractory myositis

Reed, AM and Crowson, CS and Hein, M and de Padilla, CL and Olazagasti, JM and Aggarwal, R and Ascherman, DP and Levesque, MC and Oddis, CV (2015) Biologic predictors of clinical improvement in rituximab-treated refractory myositis. BMC musculoskeletal disorders, 16. 257 - ?.

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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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Reed, AM
Crowson, CS
Hein, M
de Padilla, CL
Olazagasti, JM
Aggarwal, Rroa19@pitt.eduROA19
Ascherman, DP
Levesque, MC
Oddis, CVcvo5@pitt.eduCVO5
Date: 17 September 2015
Date Type: Publication
Journal or Publication Title: BMC musculoskeletal disorders
Volume: 16
Page Range: 257 - ?
DOI or Unique Handle: 10.1186/s12891-015-0710-3
Refereed: Yes
Date Deposited: 09 Aug 2016 16:43
Last Modified: 13 Oct 2017 17:55
URI: http://d-scholarship.pitt.edu/id/eprint/29197

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