After 15 months of treatment with etanercept, about one-third of a cohort of children with juvenile idiopathic arthritis achieved an excellent response.
Those children who were most likely to respond had relatively recent JIA and had tried fewer other treatments prior to undertaking etanercept therapy. Those who fared poorly on etanercept were more likely to have systemic-onset disease than the others; however, a quarter of systemic-onset patients achieved an excellent response. Female sex was also associated with a poor treatment outcome.
This study of 262 children with JIA is part of a multicenter, prospective, observational register, the Arthritis and Biologics in Children (ABC) Register, which was founded with the introduction of biologics in 1999 and includes all JIA patients in the Netherlands who use or previously used biological agents.
The findings, published online Nov. 6 in JAMA (2011 [doi:10.1001/jama.2011.1671]), were simultaneously presented at the American College of Rheumatology annual scientific meeting in Chicago by Dr. Marieke H. Otten, of the pediatrics department at Erasmus Medical Center, Rotterdam, the Netherlands.
Dr. Otten and her colleagues enrolled all patients registered before October 2009 who had not been treated with a biologic agent before etanercept. Of the 262 study subjects, 71% were female and 18% had systemic-onset JIA. The median age when starting etanercept was 12.4 years.
Most of the subjects – 89% – were also taking methotrexate at the start of the study period, and more than a third were taking corticosteroids. However 69% of patients on steroids had discontinued them by the end of the study period, and 42% of patients on methotrexate had discontinued using that agent.
After 15 months of treatment with etanercept, 32% of patients were graded as excellent responders, with no clinical evidence of arthritis, uveitis, or systemic disease; 36% were intermediate responders, with 50% or better improvement using American College of Rheumatology pediatric (ACRpedi) criteria for JIA; and 32% were poor responders, defined as not achieving at least an ACRpedi 50 response after 15 months on etanercept, or discontinuing before 15 months due to ineffectiveness or adverse events.
Excellent response was associated with lower baseline scores on the Childhood Health Assessment Questionnaire (adjusted odds ratio per point increase, 0.49; 95% confidence interval, 0.33-0.74); use of fewer disease-modifying antirheumatic drugs (DMARDs, including methotrexate) before starting etanercept (adjusted OR per DMARD used, 0.64; 95% CI, 0.43-0.95); and younger age at disease onset (adjusted OR per year increase, 0.92; 95% CI, 0.84-0.99).
Having systemic-onset JIA was strongly associated with poor response, with systemic-onset patients three times more likely to see a poor treatment outcome than those with nonsystemic disease (adjusted OR systemic JIA vs. nonsystemic, 2.92; 95% CI, 1.26-6.80). However, Dr. Otten and her colleagues noted in their analysis that some 11 of the 46 patients (24%) with systemic-onset JIA nonetheless were able to reach inactive disease after 15 months on etanercept.
Female sex was also associated with poor response (adjusted OR female vs. male, 2.16; 95% CI, 1.12-4.18).
In the first 15 months of treatment, 119 of the patients in the cohort experienced an adverse event, and 13 discontinued because of adverse effects, including a total of 31 serious, 99 infectious, and 179 noninfectious adverse events. These occurred in 37 patients with an excellent response, 36 with an intermediate response, and 46 with a poor response.
Dr. Otten and her colleagues were not able to identify baseline factors predictive of adverse effects, although a possible association was seen between methotrexate use within the first 15 months of etanercept treatment and infectious adverse events. That association did not reach statistical significance.
In a secondary analysis of 262 patients with a median follow-up of 35.6 months after starting etanercept, between 37% and 49% of patients had reached inactive disease.
The investigators noted as a strength of their study the fact that it included all biological treatment–naïve JIA children and adolescents taking etanercept in the Netherlands during the study period, thereby reducing the likelihood of selection bias.
They noted as a key weakness the study’s design, which included no control group. Therefore, they wrote in their analysis, "it remains unknown whether patients with a poor response to etanercept would have responded better to other treatment options." The findings, they said, "mainly reflect overall prognostic factors [rather] than predictive factors for etanercept treatment in particular."
Funding for the ABC Register came from the Dutch Board of Health Insurance, Pfizer, and Abbott. Dr. Otten and several coauthors have received grants, fees, or other forms of support from Abbott, Bristol-Myers Squibb, Novartis, Pfizer, Roche, or Tevapharma.