Response to Etanercept in Juvenile Idiopathic Arthritis

After 15 months of therapy with etanercept, a tumor necrosis factor alpha antagonist, patients with juvenile idiopathic arthritis (JIA) who had had low baseline disability scores, prior disease-modifying antirheumatic drug (DMARD) use, and developed JIA at a young age were more likely to have achieved an excellent response, according to results of a recent study [JAMA. 2011;306(21):2340-2347]. The advent of biologic agents has greatly changed the treatment of JIA, and the use of DMARDs used earlier on in the course of the disease has led to improved long-term outcomes for patients. Although a treatment goal of inactive disease has become more realistic, it is still not achieved in a number of patients. Seeking to better identify patients more likely to respond to etanercept treatment, researchers recently conducted a study to evaluate disease activity in 262 patients with JIA who began taking etanercept as their first biologic treatment and to identify any baseline characteristics associated with etanercept treatment response. The study was part of a multicenter prospective observational register known as the ABC Register, which includes all JIA patients in the Netherlands who use or previously used biologic agents. Patients were followed up for a minimum of 15 months. The researchers collected data on patient and disease characteristics at baseline, after 3 months of treatment, and then yearly. Data collected were part of the JIA disease activity score (the JIA core set): physician’s global assessment of disease activity on a visual analog scale; the Childhood Health Assessment Questionnaire (CHAQ); number of active and limited joints; and erythrocyte sedimentation rate (ESR). The researchers assessed patients’ response to therapy using the ACRpedi 30, 50, and 70 criteria (30%, 50%, or 70% improvement from baseline in ≥3 variables of the JIA core set and ≤1 variable worsening by >30%). Inactive disease was defined as no active arthritis, no systemic features, no uveitis, normal ESR, and physician’s global assessment of disease activity indicating no disease activity. The researchers also examined the following baseline factors for treatment response: sex, age of JIA onset, disease duration until etanercept treatment initiation, antinuclear antibody positivity, JIA category (systemic onset vs all other categories), number of DMARDs (including methotrexate) used before etanercept, physician’s global assessment of disease activity at initiation of etanercept, CHAQ score, and ESR. Excellent treatment response was defined as achievement of inactive disease after 15 months; intermediate response as an ACRpedi score of 50 after 15 months, and poor response as no achievement of an ACRpedi score of 50 after 15 months (or discontinuation due to ineffectiveness or adverse events). The researchers used the Mann-Whitney U test and the Pearson χ2 test to perform comparisons and univariable and multivariable logistic regression to identify potential baseline factors associated with achieved treatment response. By 15 months after treatment, 85 of 262 patients (32%) were classified as excellent responders, 85 were considered poor responders (32%), and the remaining 92 patients were classified as intermediate responders. The researchers found that the achievement of an excellent treatment response was related to lower baseline CHAQ scores (adjusted odds ratio [OR], 0.49), low number of DMARDs (including methotrexate) used before the introduction of etanercept (adjusted OR per DMARD used, 0.64), and a younger age at onset of JIA (adjusted OR per year increase, 0.92). The achievement of a poor response was associated with systemic JIA (adjusted OR for systemic JIA vs nonsystemic JIA, 2.92) and being female (adjusted OR for female vs male sex, 2.16). A key limitation of the study was the lack of a control group, and the researchers noted that head-to-head trials of biologic agents for the treatment of JIA are still needed.