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01.12.2015 | Research article | Ausgabe 1/2015 Open Access

BMC Musculoskeletal Disorders 1/2015

Biologic predictors of clinical improvement in rituximab-treated refractory myositis

Zeitschrift:
BMC Musculoskeletal Disorders > Ausgabe 1/2015
Autoren:
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
Wichtige Hinweise

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

JO drafted the manuscript and helped perform the statistical analysis. CC participated in the design of the study and performed the statistical analysis. MH, CL, RA, DA, ML, CO and AR conceived the study, and participated in its design and coordination. All authors read and approved the final manuscript.

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.
Literatur
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