Search

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.

Objective Over the past decade, the availability of biological agents for the treatment of juvenile idiopathic arthritis ( JIA) has increased substantially. Because direct head-to-head trials comparing these agents are lacking, we indirectly compared their efficacy. Methods In a systematic review, all available efficacy data from randomised controlled trials performed in JIA with inclusion of biological agents were retrieved. Indirect between-drug comparisons (based on Bucher’s method) were conducted only if trials were comparable with regard to design and patients’ characteristics related to treatment outcome. Results We identified 11 randomised controlled trials. On the basis of the equality of the trials, six trials were grouped into two networks of evidence. Network 1 included withdrawal trials which evaluated etanercept, adalimumab and abatacept in polyarticular course JIA. Indirect comparisons identified no significant differences in short-term efficacy. Network 2 indirectly compared trials with a parallel study design investigating anakinra, tocilizumab and canakinumab in systemic JIA; no differences in comparative efficacy were identified. Although the two networks were constructed on the basis of comparability, small differences in trial design and case mix still existed. Conclusions Because of the small number of trials and the observed differences between trials, no definite conclusions could be drawn about the comparative effectiveness of the indirectly compared biological agents. Therefore, for now, the paediatric rheumatologist has to rely on observational data and safety, practical and financial arguments. Comparability of future trials needs to be improved, and head-to-head trials are required to decide on the best biological treatment for JIA.

Since 1999, the treatment of juvenile idiopathic arthritis (JIA) has been extended with a new category of drugs: biologic agents (also known as biologicals or biologic disease modifying anti-rheumatic drugs). Biologic agents consist of natural proteins, like antibodies and cytokines, and have been developed to target one or more steps of the immune response. Elucidation of many of the cellular and molecular mechanisms of the immune system involved in inflammatory arthritis has resulted in an increasing development of different biologic agents and, in the future, this number will expand even further. Tumour necrosis factor (TNF) is a proinflammatory cytokine that plays a central role in the pathogenesis of juvenile idiopathic arthritis. In systemic disease, interleukin (IL)-1 (a proinflammatory cytokine synthesised by fibroblasts in the synovium and macrophages) and IL-6 (concentrations of which correlate with fever, disease activity, and platelet counts) are also thought to be important. If inhibition of these cytokines is not sufficient, other drugs that aim at T cell blockade and B cell depletion are available. Only etanercept (TNF-alpha receptor antagonist), adalimumab (anti-TNF-alpha antibody), abatacept (selective T-cell co-stimulation modulator) and tocilizumab (IL-6 receptor antibody) have been approved by the European Medicines Agency and the Food and Drug Administration for the treatment of JIA. Until now, also infliximab (anti-TNF-alpha antibody), anakinra (IL-1 receptor antagonist), canakinumab (anti-IL-1 antibody) and rilonacept (IL-1 receptor antagonist), though not approved, are available options or under investigation for the treatment of JIA. All of the above mentioned agents have been studied in randomized controlled clinical trials with inclusion of JIA patients.But after approval and sometimes off-label use in daily clinical practice, prospective observational studies are crucial to evaluate the longterm effectiveness and safety in a non-selected

Objective. To evaluate the effectiveness and safety of biological agents in children with enthe - sitis-related arthritis (ERA). Methods. All patients with ERA in whom a biological agent was initiated between 1999 and 2010 were selected from the Dutch Arthritis and Biologicals in Children (ABC) register. In this ongoing multicenter observational register, data on the course of the disease and medication use are retrieved prospectively at the start of the biological agent, after 3 months, and yearly thereafter. Inactive disease was assessed in accordance with the Wallace criteria. Results. Twenty-two patients with ERA started taking 1 or more biological agents: 20 took etanercept, 2 took adalimumab (1 switched from etanercept to adalimumab), and 2 took infliximab (1 switched from etanercept to infliximab). Characteristics: 77% were male, 77% had enthesitis, 68% were HLA-B27-positive. The median age of onset was 10.4 (IQR 9.4-12.0) years; median follow-up from the start of the biological agent was 1.2 (IQR 0.5-2.4) years. Intention-to-treat analysis shows that inactive disease was achieved in 7 of 22 patients (32%) after 3 months, 5 of 13 patients (38%) after 15 months, and 5 of 8 patients (63%) after 27 months of treatment. Two patients discontinued etanercept because of ineffectiveness, and switched to adalimumab (inactive disease achieved) or infliximab (decline in joints with arthritis after 3 months of treatment). One patient discontinued etanercept because of remission, but had flare and restarted treatment, with good clinical response. No serious adverse events occurred. Conclusion. Tumor necrosis factor (TNF)-blocking agents seem effective and safe for patients with ERA that was previously unresponsive to 1 or more DMARD. However, a sustained disease-free state could not be achieved, and none discontinued TNF-blocking agents successfully. The Journal of Rheumatology Copyright