Cargando…

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

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 treatme...

Descripción completa

Detalles Bibliográficos
Autores principales: Anink, Janneke, Van Suijlekom-Smit, Lisette W. A., Otten, Marieke H., Prince, Femke H. M., van Rossum, Marion A. J., Dolman, Koert M., Hoppenreijs, Esther P. A. H., ten Cate, Rebecca, Ursu, Simona, Wedderburn, Lucy R., Horneff, Gerd, Frosch, Michael, Vogl, Thomas, Gohar, Faekah, Foell, Dirk, Roth, Johannes, Holzinger, Dirk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528380/
https://www.ncbi.nlm.nih.gov/pubmed/26249667
http://dx.doi.org/10.1186/s13075-015-0723-1
_version_ 1782384677588303872
author Anink, Janneke
Van Suijlekom-Smit, Lisette W. A.
Otten, Marieke H.
Prince, Femke H. M.
van Rossum, Marion A. J.
Dolman, Koert M.
Hoppenreijs, Esther P. A. H.
ten Cate, Rebecca
Ursu, Simona
Wedderburn, Lucy R.
Horneff, Gerd
Frosch, Michael
Vogl, Thomas
Gohar, Faekah
Foell, Dirk
Roth, Johannes
Holzinger, Dirk
author_facet Anink, Janneke
Van Suijlekom-Smit, Lisette W. A.
Otten, Marieke H.
Prince, Femke H. M.
van Rossum, Marion A. J.
Dolman, Koert M.
Hoppenreijs, Esther P. A. H.
ten Cate, Rebecca
Ursu, Simona
Wedderburn, Lucy R.
Horneff, Gerd
Frosch, Michael
Vogl, Thomas
Gohar, Faekah
Foell, Dirk
Roth, Johannes
Holzinger, Dirk
author_sort Anink, Janneke
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-015-0723-1) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4528380
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-45283802015-08-08 MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis Anink, Janneke Van Suijlekom-Smit, Lisette W. A. Otten, Marieke H. Prince, Femke H. M. van Rossum, Marion A. J. Dolman, Koert M. Hoppenreijs, Esther P. A. H. ten Cate, Rebecca Ursu, Simona Wedderburn, Lucy R. Horneff, Gerd Frosch, Michael Vogl, Thomas Gohar, Faekah Foell, Dirk Roth, Johannes Holzinger, Dirk Arthritis Res Ther Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-015-0723-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-08-07 2015 /pmc/articles/PMC4528380/ /pubmed/26249667 http://dx.doi.org/10.1186/s13075-015-0723-1 Text en © Anink et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Anink, Janneke
Van Suijlekom-Smit, Lisette W. A.
Otten, Marieke H.
Prince, Femke H. M.
van Rossum, Marion A. J.
Dolman, Koert M.
Hoppenreijs, Esther P. A. H.
ten Cate, Rebecca
Ursu, Simona
Wedderburn, Lucy R.
Horneff, Gerd
Frosch, Michael
Vogl, Thomas
Gohar, Faekah
Foell, Dirk
Roth, Johannes
Holzinger, Dirk
MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis
title MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis
title_full MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis
title_fullStr MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis
title_full_unstemmed MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis
title_short MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis
title_sort mrp8/14 serum levels as a predictor of response to starting and stopping anti-tnf treatment in juvenile idiopathic arthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528380/
https://www.ncbi.nlm.nih.gov/pubmed/26249667
http://dx.doi.org/10.1186/s13075-015-0723-1
work_keys_str_mv AT aninkjanneke mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT vansuijlekomsmitlisettewa mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT ottenmariekeh mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT princefemkehm mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT vanrossummarionaj mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT dolmankoertm mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT hoppenreijsestherpah mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT tencaterebecca mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT ursusimona mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT wedderburnlucyr mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT horneffgerd mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT froschmichael mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT voglthomas mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT goharfaekah mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT foelldirk mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT rothjohannes mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis
AT holzingerdirk mrp814serumlevelsasapredictorofresponsetostartingandstoppingantitnftreatmentinjuvenileidiopathicarthritis