TY - JOUR
T1 - Biologic predictors of clinical improvement in rituximab-treated refractory myositis Clinical rheumatology and osteoporosis
AU - Reed, Ann M.
AU - Crowson, Cynthia S.
AU - Hein, Molly
AU - De Padilla, Consuelo Lopez
AU - Olazagasti, Jeannette M.
AU - Aggarwal, Rohit
AU - Ascherman, Dana P.
AU - Levesque, Marc C.
AU - Oddis, Chester V.
N1 - Funding Information:
We would like to thank Peter Wettstein, PhD and Micheal Strausbauch from the Immune Monitoring Laboratory, Mayo Clinic, Rochester, MN, for their role in generating the cytokine/chemokine data. Also Diane Koontz, University of Pittsburgh Medical Center, Pittsburgh, PA for the coordination of sample retrieval and shipment. Lastly, we would like to thank the RIM investigators and subjects. This work was supported by the National Institute for Health: Mechanisms of Response and Relapse in Rituximab-treated Refractory Idiopathic Inflammatory Myopathies [AR61298-03]; and the National Institute of Arthritis and Musculoskeletal and Skin Diseases [N01-AR-4-2273, R01 AR061298].
Publisher Copyright:
© 2015 Reed et al.
PY - 2015/9/17
Y1 - 2015/9/17
N2 - 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.
AB - 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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U2 - 10.1186/s12891-015-0710-3
DO - 10.1186/s12891-015-0710-3
M3 - Article
C2 - 26382217
AN - SCOPUS:84941919881
VL - 16
JO - BMC Musculoskeletal Disorders
JF - BMC Musculoskeletal Disorders
SN - 1471-2474
IS - 1
M1 - 257
ER -