Methods

PK samples for this analysis were obtained during routine study visits of the Randomized Placebo Phase study Of Rilonacept in the Treatment of sJIA (RAPPORT, 2007–2012, NCT00534495). 10 RAPPORT was a multicenter, prospective, randomized, controlled, placebo-phase, double-blind study of rilonacept in 75 children 1–18 years of age with active sJIA. Two treatment arms were randomized 1: 1 to the following groups—Group A: rilonacept loading SC dose of 4.4 mg/kg given at day 0 and then once weekly at a dose of 2.2 mg/kg throughout the 24-week study; Group B: placebo SC doses at days 0, 7, 14, and 21 followed by a loading dose of rilonacept (4.4 mg/kg) on day 28, and then rilonacept at 2.2 mg/kg once weekly thereafter until completion of 24 weeks. This design was meant to assess rilonacept efficacy by measuring a potential difference in time to response in Group B who received the active drug 4 week later than Group A. The study was approved by the institutional review boards at each institution, and informed consent was obtained from a parent or guardian prior to enrollment. Assent was obtained when possible in children≥ 7 years of age.

Sparse PK sampling occurred at 3 time points; within 2 hours prior to administration of study drug at weeks 4, 14, and 24 post-randomization. Exact timing of rilonacept administration was not recorded and was assumed to occur 2 hours after PK sample collection. Dosing time was therefore imputed from the time of PK sample collection. Blood was collected in a 4.5 mL CTAD tube and centrifuged at 1,500 X g and 4 C for 10 minutes immediately prior to freezing at the study sites. PK samples were sent to Quest Diagnostics for storage at− 70 C prior to analysis.