To determine the long‐term safety and efficacy of rilonacept, an anti–interleukin‐1 fusion protein, in patients with active systemic juvenile idiopathic arthritis (JIA).

In patients with systemic JIA, ages 4–20 years, the efficacy of rilonacept was evaluated using 30%, 50%, and 70% levels of improvement according to the adapted American College of Rheumatology (ACR) Pediatric 30, 50, and 70 response criteria, respectively. Efficacy and safety were evaluated during 23 months of open‐label treatment (3 phases) after a 4‐week, double‐blind, placebo‐controlled phase. Following double‐blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept, patients were eligible to receive open‐label treatment at their prior dose, with adjustments. Reductions in the median daily dose of oral prednisone and improvements in laboratory parameters of disease activity (i.e., decreased levels of D‐dimer and myeloid‐related proteins [MRPs]) were also evaluated.

Twenty‐four patients entered the double‐blind study and 23 entered the open‐label period. Patients were predominantly white and female, and had a median age of 14.0 years at baseline. No significant differences in efficacy were observed between the rilonacept‐ and placebo‐treated patients during the double‐blind phase, but fever and rash completely resolved by month 3 in all patients during the open‐label treatment period and did not recur. Adapted ACR Pediatric 30, 50, and 70 response rates at 3 months from the start of the study were 78.3%, 60.9%, and 34.8%, respectively; these responses were generally maintained over the study duration. Levels of D‐dimer and MRP‐8/MRP‐14 dramatically improved during the study, and in 22 of 23 patients, the prednisone dose was decreased or prednisone therapy was discontinued. No serious treatment‐related adverse events were observed.

Sustained improvements in clinical and laboratory measures of the articular and systemic manifestations of systemic JIA were achieved in >50% of rilonacept‐treated patients over 2 years. Treatment with rilonacept had a substantial steroid‐sparing effect and was generally well‐tolerated.