In study 3, the majority of patients (77%) who were initially randomised to 50 mg twice weekly and had their etanercept dose decreased at week 12 to 25 mg twice weekly maintained their PASI 75 response through week 36. For patients who received 25 mg twice weekly throughout the study, the PASI 75 response continued to improve between weeks 12 and 36. In study 4, the etanercept-treated group had a higher proportion of patients with PASI 75 at week 12 (38%) compared to the placebo-treated group (2%) (p weekly throughout the study, the efficacy responses continued to improve with 71% achieving PASI 75 at week 24.
In long-term (up to 34 months) open-label studies where etanercept was given without interruption, clinical responses were sustained and safety was comparable to shorter-term studies. An analysis of clinical trial data did not reveal any baseline disease characteristics that would assist clinicians in selecting the most appropriate dosing option (intermittent or continuous). Consequently, the choice of intermittent or continuous therapy should be based upon physician judgment and individual patient needs. Antibodies to etanercept Antibodies to etanercept have been detected in the sera of some subjects treated with etanercept.
These antibodies have all been non-neutralising and are generally transient. There appears to be no correlation between antibody development and clinical response or adverse events. Paediatric population Paediatric patients with juvenile idiopathic arthritis The safety and efficacy of etanercept were assessed in a two-part study in 69 children with polyarticular course juvenile idiopathic arthritis who had a variety of juvenile idiopathic arthritis onset types (polyarthritis, pauciarthritis, systemic onset).
Patients aged 4 to 17 years with moderately to severely active polyarticular-course juvenile idiopathic arthritis refractory to, or intolerant of, methotrexate were enrolled; patients remained on a stable dose of a single non-steroidal anti-inflammatory drug and/or prednisone ( 25 mg per dose) etanercept subcutaneously twice weekly. In part 2, patients with a clinical response at day 90 were randomised to remain on etanercept or receive placebo for four months and assessed for disease flare.
Responses were measured using the ACR Pedi 30, defined as ≥ 30% improvement in at least three of six and ≥ 30% worsening in no more than one of six JRA core set criteria, including active joint count, limitation of motion, physician and patient/parent global assessments, functional assessment, and erythrocyte sedimentation rate (ESR). Disease flare was defined as a ≥ 30% worsening in three of six JRA core set criteria and ≥ 30% improvement in not more than one of the six JRA core set criteria and a minimum of two active joints. In part 1 of the study, 51 of 69 (74%) patients demonstrated a clinical response and entered part 2.
In part 2, 6 of 25 (24%) patients remaining on etanercept experienced a disease flare compared to 20 of 26 (77%) patients receiving placebo (p = 0.007). From the start of part 2, the median time to flare was ≥ 116 days for patients who received etanercept and 28 days for patients who received placebo. Of patients who demonstrated a clinical response at 90 days and entered part 2 of the study, some of the patients remaining on etanercept continued to improve from month 3 through month 7, while those who received placebo did not improve.
In an open-label, safety extension study, 58 paediatric patients from the above study (from the age of 4 years at time of enrolment) continued to receive etanercept for up to 10 years. Rates of serious adverse events and serious infections did not increase with long-term exposure. 26