Abstract

ObjectivesTo determine (i) correlates for etanercept (ETA) discontinuation after achieving an inactive disease and for the subsequent risk of flare and (ii) to analyze the effectiveness of ETA in the re-treatment after a disease flare.MethodsData from two ongoing prospective registries, BiKeR and JuMBO, were used for the analysis. Both registries provide individual trajectories of clinical data and outcomes from childhood to adulthood in juvenile idiopathic arthritis (JIA) patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) and conventional synthetic DMARDs (csDMARDs).ResultsA total of 1724 patients were treated first with ETA treatment course (338 with second, 54 with third ETA course). Similar rates of discontinuation due to ineffectiveness and adverse events could be observed for the first (19.4%/6.2%), second (18.6%/5.9%), and third (14.8%/5.6%) ETA course. A total of 332 patients (+/−methotrexate, 19.3%) discontinued ETA after achieving remission with the first ETA course. Younger age (hazard ratio (HR) 1.08, p < 0.001), persistent oligoarthritis (HR 1.89, p = 0.004), and shorter duration between JIA onset and ETA start (HR 1.10, p < 0.001), as well as good response to therapy within the first 6 months of treatment (HR 1.11, p < 0.001) significantly correlated to discontinuation with inactive disease. Reoccurrence of active disease was reported for 77% of patients with mean time to flare of 12.1 months. We could not identify any factor correlating to flare risk. The majority of patients were re-treated with ETA (n = 117 of 161; 72.7%) after the flare. One in five patients (n = 23, 19.7%) discontinued ETA again after achieving an inactive disease and about 70% of the patients achieved an inactive disease 12 months after restarting ETA.ConclusionThe study confirms the effectiveness of ETA even for re-treatment of patients with JIA. Our data highlight the association of an early bDMARD treatment with a higher rate of inactive disease indicating a window of opportunity.

Highlights

  • Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children and adolescents

  • An early Biologic diseasemodifying anti-rheumatic drugs (bDMARDs) treatment was associated with a higher likelihood to achieve inactive disease state and discontinue etanercept, indicating a window of opportunity

  • Patients who were re-treated responded well to etanercept in the second treatment course after discontinuing etanercept by inactive disease

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Summary

Introduction

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children and adolescents. According to the currently valid International League of Associations for Rheumatology (ILAR) classification [1, 2], JIA comprises six different forms of arthritis that begin before the age of 16 and differ from each other in clinical presentation, course, response to therapy, genetic background, and extraarticular manifestations. They all share one feature: consistent therapy is required to avoid consequential damage and permanent loss of function. The main treatment principles include tumor necrosis factor (TNF)-α receptor antagonists (etanercept (ETA), adalimumab (ADA), golimumab, the interleukin (IL)-6 pathway inhibitor (tocilizumab (TOC)), and IL-1 pathway inhibitors (anakinra and canakinumab)), and the T-cell co-stimulatory signal modulator abatacept, among others

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