Abstract
IntroductionApproximately 30 % of juvenile idiopathic arthritis (JIA) patients fail to respond to anti-TNF treatment. When clinical remission is induced, some patients relapse after treatment has been stopped. We tested the predictive value of MRP8/14 serum levels to identify responders to treatment and relapse after discontinuation of therapy.MethodsSamples from 88 non-systemic JIA patients who started and 26 patients who discontinued TNF-blockers were analyzed. MRP8/14 serum levels were measured by in-house MRP8/14 ELISA and by Bühlmann Calprotectin ELISA at start of anti-TNF treatment, within 6 months after start and at discontinuation of etanercept in clinical remission. Patients were categorized into responders (ACRpedi ≥ 50 and/or inactive disease) and non-responders (ACRpedi < 50) within six months after start, response was evaluated by change in JADAS-10. Disease activity was assessed within six months after discontinuation.ResultsBaseline MRP8/14 levels were higher in responders (median MRP8/14 of 1466 ng/ml (IQR 1045–3170)) compared to non-responders (median MRP8/14 of 812 (IQR 570–1178), p < 0.001). Levels decreased after start of treatment only in responders (p < 0.001). Change in JADAS-10 was correlated with baseline MRP8/14 levels (Spearman’s rho 0.361, p = 0.001). Patients who flared within 6 months after treatment discontinuation had higher MRP8/14 levels (p = 0.031, median 1025 ng/ml (IQR 588–1288)) compared to patients with stable remission (505 ng/ml (IQR 346–778)). Results were confirmed by Bühlmann ELISA with high reproducibility but different overall levels.ConclusionHigh levels of baseline MRP8/14 are associated with good response to anti-TNF treatment, whereas elevated MRP8/14 levels at discontinuation of etanercept are associated with higher chance to flare.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0723-1) contains supplementary material, which is available to authorized users.
Highlights
30 % of juvenile idiopathic arthritis (JIA) patients fail to respond to anti-tumor necrosis factor (TNF) treatment
Baseline characteristics Baseline serum samples were available from 88 patients with non-systemic JIA to measure MRP8/14 levels with the in-house enzyme-linked immunosorbent assay (ELISA) and of these 81 were available to perform both in-house and commercial ELISA
childhood health assessment questionnaire (CHAQ) at baseline, number of active joints and disease activity expressed as juvenile arthritis disease activity score (JADAS)-10 were not correlated with MRP8/14 levels
Summary
30 % of juvenile idiopathic arthritis (JIA) patients fail to respond to anti-TNF treatment. MRP8/14 serum levels correlate with disease activity in JIA patients [8], can be used to identify subclinical disease activity, and are associated with flares in JIA patients in clinical remission on methotrexate (MTX) [9, 10]. This biomarker correlates closely to response to treatment in patients with systemic JIA [11] and is able to predict good response to MTX in a subset of patients with non-systemic JIA [12]
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