Long-term safety of etanercept monotherapy (n = 103), etanercept plus methotrexate (n = 294), or methotrexate monotherapy (n = 197) were assessed for up to 3 years in a registry of 594 children aged 2 to 18 years with juvenile idiopathic arthritis, 39 of whom were 2 to 3 years of age. Overall, infections were more commonly reported in patients treated with etanercept compared to methotrexate alone (3.8 versus 2%), and the infections associated with etanercept use were of a more severe nature.
In another open-label single-arm study (n=127), 60 patients with extended oligoarthritis (EO) (15 patients aged 2 to 4, 23 patients aged 5 to 11 and 22 patients aged 12 to 17 years old), 38 patients with enthesitis-related arthritis (12 to 17 years old), and 29 patients with psoriatic arthritis (12 to 17 years old) were treated with etanercept at a dose of 0.8 mg/kg (up to a maximum of 50 mg per dose) administered weekly for 12 weeks. In each of the JIA subtypes, the majority of patients met ACR Pedi 30 criteria and demonstrated clinical improvement in secondary endpoints such as number of tender joints and physician global assessment.
The safety profile was consistent with that observed in other JIA studies. Of the 127 patients in the parent study, 109 participated in the open-label extension study and were followed for an additional 8 years for a total of up to 10 years. At the end of the extension study, 84/109 (77%) patients had completed the study; 27 (25%) while actively taking etanercept, 7 (6%) had withdrawn from treatment due to low/inactive disease; 5 (5%) had re-started etanercept following an earlier withdrawal from treatment; and 45 (41%) had stopped etanercept (but remained under observation); 25/109 (23%) patients permanently discontinued from the study.
Improvements in clinical status achieved in the parent study were generally maintained for all efficacy endpoints during the entire follow-up period. Patients actively taking etanercept could enter an optional withdrawal-retreatment period once during the extension study based on investigator’s judgement of clinical response. 30 patients entered the withdrawal period. 17 patients were reported to have a flare (defined as ≥ 30% worsening in at least 3 of the 6 ACR Pedi components with ≥ 30% improvement in not more than 1 of the remaining 6 components and a minimum of 2 active joints); median time to flare after etanercept withdrawal was 190 days.
13 patients were re-treated and the median time to re-treatment from withdrawal was estimated as 274 days. Due to the small number of data points, these results should be interpreted with caution. The safety profile was consistent with that observed in the parent study. Studies have not been done in patients with juvenile idiopathic arthritis to assess the effects of continued etanercept therapy in patients who do not respond within 3 months of initiating etanercept therapy. Additionally, studies have not been conducted to assess the effects of reducing the recommended dose of etanercept following its long-term use in patients with JIA.
Paediatric patients with plaque psoriasis The efficacy of etanercept was assessed in a randomised, double-blind, placebo-controlled study in 211 paediatric patients aged 4 to 17 years with moderate to severe plaque psoriasis (as defined by an sPGA score ≥ 3, involving ≥ 10% of the BSA, and PASI ≥ 12). Eligible patients had a history of receiving phototherapy or systemic therapy, or were inadequately controlled on topical therapy. Patients received etanercept 0.8 mg/kg (up to 50 mg) or placebo once weekly for 12 weeks. At week 12, more patients randomised to etanercept had positive efficacy responses (e.g., PASI 75) than those randomised to placebo. 27