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 Clinical rheumatology and osteoporosis.
BMC Musculoskeletal Disorders, 16 (1).
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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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
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Reed, AM | | | | Crowson, CS | | | | Hein, M | | | | De Padilla, CL | | | | Olazagasti, JM | | | | Aggarwal, R | roa19@pitt.edu | ROA19 | | Ascherman, DP | | | | Levesque, MC | | | | Oddis, CV | cvo5@pitt.edu | CVO5 | |
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Date: |
17 September 2015 |
Date Type: |
Publication |
Journal or Publication Title: |
BMC Musculoskeletal Disorders |
Volume: |
16 |
Number: |
1 |
DOI or Unique Handle: |
10.1186/s12891-015-0710-3 |
Refereed: |
Yes |
Date Deposited: |
09 Aug 2016 16:43 |
Last Modified: |
30 Mar 2021 10:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/29197 |
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