Abstract
BackgroundTo 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.MethodsIn 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.ResultsThe 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).ConclusionBiomarker signatures in conjunction with autoAbs help predict response to rituximab in refractory myositis. Biomarker and clinical responses are greatest at 16 weeks after rituximab.
Highlights
To examine the longitudinal utility of a biomarker signature in conjunction with myositis autoantibodies as predictors of disease improvement in refractory myositis patients treated with rituximab
They analyzed the effect of diverse variables such as myositis autoantibodies at baseline as predictors of the time to improvement. They found that anti-synthetase and anti-Mi-2 autoantibodies strongly predicted improvement in rituximab-treated refractory myositis patients [8]. Taking into account these recent findings, we examined the longitudinal utility of a biomarker signature in conjunction with myositis autoantibodies as biomarkers of disease outcome in refractory myositis patients treated with B cell depletion (BCD)
[1] We found that interferon chemokine (IFNCK) scores 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) (Table 1, Fig. 1)
Summary
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. The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of chronic acquired disorders characterized by muscle inflammation and proximal muscle weakness. These include adult polymyositis (PM), and both adult and juvenile dermatomyositis (DM) [1]. Both manual muscle testing (MMT) and serum levels of muscle enzymes have been used as markers of disease activity for IIM [2]. Detection of myositis-specific autoantibodies (MSAs) can be helpful in the proper clinical scenario. While very specific for IIM, anti-Jo-1 has a low sensitivity, and is only present in 20–30 % of PM patients and even less frequently in DM patients (5–10 %)
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