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Open Access 01-12-2015 | Research article

Biologic predictors of clinical improvement in rituximab-treated refractory myositis

Authors: Ann M. Reed, Cynthia S. Crowson, Molly Hein, Consuelo Lopez de Padilla, Jeannette M. Olazagasti, Rohit Aggarwal, Dana P. Ascherman, Marc C. Levesque, Chester V. Oddis, the RIM Study Group

Published in: BMC Musculoskeletal Disorders | Issue 1/2015

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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Title: Biologic predictors of clinical improvement in rituximab-treated refractory myositis
Authors: Ann M. Reed
Cynthia S. Crowson
Molly Hein
Consuelo Lopez de Padilla
Jeannette M. Olazagasti
Rohit Aggarwal
Dana P. Ascherman
Marc C. Levesque
Chester V. Oddis
the RIM Study Group
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Musculoskeletal Disorders / Issue 1/2015
Electronic ISSN: 1471-2474
DOI: https://doi.org/10.1186/s12891-015-0710-3

At a glance: The STEP trials

Springer Medicine

Biologic predictors of clinical improvement in rituximab-treated refractory myositis

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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