title: MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics/ Pediatric Rheumatology, Erasmus MC Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands. j.anink@erasmusmc.nl.
authors.forename: Janneke
authors.initials: J
authors.lastname: Anink
authors.affiliation: Department of Pediatrics/ Pediatric Rheumatology, Erasmus MC Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands. l.vansuijlekom@erasmusmc.nl.
authors.forename: Lisette W A
authors.initials: LW
authors.lastname: Van Suijlekom-Smit
authors.affiliation: Department of Pediatrics/ Pediatric Rheumatology, Erasmus MC Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands. m.h.otten-4@umcutrecht.nl.
authors.forename: Marieke H
authors.initials: MH
authors.lastname: Otten
authors.affiliation: Department of Pediatrics/ Pediatric Rheumatology, Erasmus MC Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands. f.h.prince@amc.uva.nl.
authors.forename: Femke H M
authors.initials: FH
authors.lastname: Prince
authors.affiliation: 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.
authors.forename: Marion A J
authors.initials: MA
authors.lastname: van Rossum
authors.affiliation: Sint Lucas Andreas Hospital and Reade location Jan van Breemen, Amsterdam, The Netherlands. k.dolman@slaz.nl.
authors.forename: Koert M
authors.initials: KM
authors.lastname: Dolman
authors.affiliation: Sint Maartenskliniek and Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. e.hoppenreijs@maartenskliniek.nl.
authors.forename: Esther P A H
authors.initials: EP
authors.lastname: Hoppenreijs
authors.affiliation: Leiden University Medical Centre, Leiden, The Netherlands. r.ten_cate@lumc.nl.
authors.forename: Rebecca
authors.initials: R
authors.lastname: ten Cate
authors.affiliation: Infection, Immunity, Inflammation and Physiological Medicine Programme UCL Institute of Child Health, University College London, London, UK. simursu@yahoo.com.
authors.forename: Simona
authors.initials: S
authors.lastname: Ursu
authors.affiliation: Infection, Immunity, Inflammation and Physiological Medicine Programme UCL Institute of Child Health, University College London, London, UK. l.wedderburn@ucl.ac.uk.
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
authors.affiliation: Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany. g.horneff@asklepios.com.
authors.forename: Gerd
authors.initials: G
authors.lastname: Horneff
authors.affiliation: German Pediatric Pain Centre, Children's and Adolescents' Hospital, Datteln, Germany. m.frosch@kinderklinik-datteln.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Frosch
authors.affiliation: Institute of Immunology, University Hospital Muenster and Interdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, Muenster, Germany. vogl@uni-muenster.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
authors.affiliation: 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.
authors.forename: Faekah
authors.initials: F
authors.lastname: Gohar
authors.affiliation: 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.
authors.forename: Dirk
authors.initials: D
authors.lastname: Foell
authors.affiliation: Institute of Immunology, University Hospital Muenster and Interdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, Muenster, Germany. rothj@uni-muenster.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.affiliation: 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.
authors.forename: Dirk
authors.initials: D
authors.lastname: Holzinger
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000097:blood*; D000293:Adolescent; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001171:Arthritis, Juvenile / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D040502:Calgranulin B / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D000068800:Etanercept / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: C435500:ABCC11 protein, human; D018528:ATP-Binding Cassette Transporters; D018501:Antirheumatic Agents; D015415:Biomarkers; D040502:Calgranulin B; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept