Factors associated with treatment response to etanercept in juvenile idiopathic arthritis

Since the introduction of biologic therapies, the pharmacological treatment approach for juvenile idiopathic arthritis (JIA) has changed substantially, with achievement of inactive disease as a realistic goal.

To determine the response to therapy after initiation of etanercept therapy among patients with JIA and to examine the association between baseline factors and response to etanercept treatment.

The Arthritis and Biologicals in Children Register, an ongoing prospective observational study since 1999, includes all Dutch JIA patients who used biologic agents. All biologically naive patients who started etanercept before October 2009 were included, with follow-up data to January 2011. Among the 262 patients, 185 (71%) were female, 46 (18%) had systemic-onset, and the median age at initiation of etanercept treatment was 12.4 years.

Excellent response (inactive disease or discontinuation earlier due to disease remission), intermediate response (more than 50% improvement from baseline, but no inactive disease), and poor response (less than 50% improvement from baseline or discontinuation earlier due to ineffectiveness or intolerance) evaluated 15 months after initiation of etanercept.

At 15 months after treatment initiation, 85 patients (32%) were considered excellent responders; 92 (36%), intermediate responders; and 85 (32%), poor responders. Compared with an intermediate or poor response, an excellent response was associated with lower baseline disability score (range, 0-3 points, with 0 being the best score; adjusted odds ratio [OR] per point increase, 0.49; 95% CI, 0.33-0.74); fewer disease-modifying antirheumatic drugs (DMARD) (including methotrexate) used before initiating etanercept (adjusted OR per DMARD used, 0.64; 95% CI, 0.43-0.95), and younger age at onset (adjusted OR per year increase, 0.92; 95% CI, 0.84-0.99). Compared with an intermediate or excellent response, a poor response was associated with systemic JIA (adjusted OR systemic vs nonsystemic categories, 2.92; 95% CI, 1.26-6.80), and female sex (adjusted OR female vs male, 2.16; 95% CI, 1.12-4.18). Within the first 15 months of etanercept treatment, 119 patients experienced 1 or more infectious, noninfectious, or serious adverse events, including 37 among those with an excellent response, 36 with an intermediate response, and 46 with a poor response. Within the first 15 months of treatment, 61 patients discontinued etanercept treatment, including 4 with an excellent response, 0 with an intermediate response, and 57 with a poor response. In a secondary analysis of 262 patients with a median follow-up of 35.6 months after initiation of etanercept, a range of 37% to 49% of patients reached inactive disease. The mean adherence to etanercept was 49.2 months (95% CI, 46.4-52.0) for patients with an excellent response after 15 months, 47.5 months (95% CI, 44.9-50.1) for patients with an intermediate response, and 17.4 months (95% CI, 13.6-21.2) for patients with a poor response.

Among patients with JIA who initiated treatment with etanercept, one-third achieved an excellent response, one-third an intermediate response, and one-third a poor response to therapy. Achievement of an excellent response was associated with low baseline disability scores, DMARDs used before initiating etanercept, and younger age at onset of JIA. Achievement of a poor treatment response was associated with systemic JIA and female sex.