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Arthritis Res Ther. 2015 Aug 7;17:200. doi: 10.1186/s13075-015-0723-1.

MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis.

Author information

1
Department of Pediatrics/ Pediatric Rheumatology, Erasmus MC Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands. j.anink@erasmusmc.nl.
2
Department of Pediatrics/ Pediatric Rheumatology, Erasmus MC Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands. l.vansuijlekom@erasmusmc.nl.
3
Department of Pediatrics/ Pediatric Rheumatology, Erasmus MC Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands. m.h.otten-4@umcutrecht.nl.
4
Department of Pediatrics/ Pediatric Rheumatology, Erasmus MC Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands. f.h.prince@amc.uva.nl.
5
Department of Pediatrics/ Pediatric Rheumatology Academic Medical Centre Emma Children's Hospital and Reade location Jan van Breemen, Amsterdam, The Netherlands. m.a.vanrossum@amc.uva.nl.
6
Sint Lucas Andreas Hospital and Reade location Jan van Breemen, Amsterdam, The Netherlands. k.dolman@slaz.nl.
7
Sint Maartenskliniek and Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. e.hoppenreijs@maartenskliniek.nl.
8
Leiden University Medical Centre, Leiden, The Netherlands. r.ten_cate@lumc.nl.
9
Infection, Immunity, Inflammation and Physiological Medicine Programme UCL Institute of Child Health, University College London, London, UK. simursu@yahoo.com.
10
Infection, Immunity, Inflammation and Physiological Medicine Programme UCL Institute of Child Health, University College London, London, UK. l.wedderburn@ucl.ac.uk.
11
Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany. g.horneff@asklepios.com.
12
German Pediatric Pain Centre, Children's and Adolescents' Hospital, Datteln, Germany. m.frosch@kinderklinik-datteln.de.
13
Institute of Immunology, University Hospital Muenster and Interdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, Muenster, Germany. vogl@uni-muenster.de.
14
Interdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, Muenster and Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany. faekah.gohar@ukmuenster.de.
15
Interdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, Muenster and Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany. dfoell@uni-muenster.de.
16
Institute of Immunology, University Hospital Muenster and Interdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, Muenster, Germany. rothj@uni-muenster.de.
17
Interdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, Muenster and Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany. dirk.holzinger@ukmuenster.de.

Abstract

INTRODUCTION:

Approximately 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.

METHODS:

Samples 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.

RESULTS:

Baseline 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.

CONCLUSION:

High 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.

PMID:
26249667
PMCID:
PMC4528380
DOI:
10.1186/s13075-015-0723-1
[Indexed for MEDLINE]
Free PMC Article

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