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

被引:61
作者
Anink, Janneke [1 ]
Van Suijlekom-Smit, Lisette W. A. [1 ]
Otten, Marieke H. [1 ]
Prince, Femke H. M. [1 ]
van Rossum, Marion A. J. [2 ,3 ]
Dolman, Koert M. [3 ,4 ]
Hoppenreijs, Esther P. A. H. [5 ,6 ]
ten Cate, Rebecca [7 ]
Ursu, Simona [8 ]
Wedderburn, Lucy R. [8 ]
Horneff, Gerd [9 ]
Frosch, Michael [10 ]
Vogl, Thomas [11 ,12 ]
Gohar, Faekah [12 ,13 ]
Foell, Dirk [12 ,13 ]
Roth, Johannes [12 ]
Holzinger, Dirk [12 ,13 ]
机构
[1] Erasmus MC Sophia Childrens Hosp Rotterdam, Dept Pediat Pediat Rheumatol, Rotterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands
[3] Reade Locat Jan van Breemen, Amsterdam, Netherlands
[4] Sint Lucas Andreas Hosp, Amsterdam, Netherlands
[5] Sint Maartensklin, Nijmegen, Netherlands
[6] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands
[7] Leiden Univ, Med Ctr, Leiden, Netherlands
[8] UCL, UCL Inst Child Hlth, Infect Immun Inflammat & Physiol Med Programme, London, England
[9] Asklepios Clin Sankt Augustin, Dept Gen Pediat, Ctr Pediat Rheumatol, St Augustin, Germany
[10] Childrens & Adolescents Hosp, German Pediat Pain Ctr, Datteln, Germany
[11] Univ Hosp Muenster, Inst Immunol, Munster, Germany
[12] Univ Hosp Muenster, Interdisciplinary Ctr Clin Res IZKF, Munster, Germany
[13] Univ Childrens Hosp Muenster, Dept Pediat Rheumatol & Immunol, Munster, Germany
关键词
DISEASE-ACTIVITY; PRELIMINARY DEFINITION; SELECT CATEGORIES; INACTIVE DISEASE; S100; PROTEINS; ETANERCEPT; REMISSION; METHOTREXATE; BIOMARKERS; VALIDATION;
D O I
10.1186/s13075-015-0723-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 Buhlmann 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 Buhlmann 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.
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