Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis.
OBJECTIVE
To assess the efficacy and safety of rilonacept, an interleukin-1 inhibitor, in a randomized, double-blind, placebo-controlled trial.


METHODS
An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multicenter design, followed by an open-label phase. Seventy-one children who had active arthritis in ≥2 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg/kg followed by 2.2 mg/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary end point was time to response, using the adapted American College of Rheumatology Pediatric 30 criteria coupled with the absence of fever and taper of the dosage of systemic corticosteroids, using prespecified criteria.


RESULTS
The time to response was shorter in the rilonacept arm than in the placebo arm (χ(2) = 7.235, P = 0.007). The secondary analysis, which used the same response criteria, showed that 20 (57%) of 35 patients in the rilonacept arm had a response at week 4 compared with 9 (27%) of 33 patients in the placebo arm (P = 0.016). Exacerbation of systemic juvenile idiopathic arthritis (JIA) was the most common severe adverse event. More patients in the rilonacept arm had elevated liver transaminase levels (including levels more than 3 times the upper limit of normal) compared with those in the placebo arm. Adverse events were similar in the 2 arms of the study.


CONCLUSIONS
Rilonacept was generally well tolerated and demonstrated efficacy in active systemic JIA.
Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York.
Norman T
NT
Ilowite
Kristi
K
Prather
Yuliya
Y
Lokhnygina
Laura E
LE
Schanberg
Melissa
M
Elder
Diana
D
Milojevic
James W
JW
Verbsky
Steven J
SJ
Spalding
Yukiko
Y
Kimura
Lisa F
LF
Imundo
Marilynn G
MG
Punaro
David D
DD
Sherry
Stacey E
SE
Tarvin
Lawrence S
LS
Zemel
James D
JD
Birmingham
Beth S
BS
Gottlieb
Michael L
ML
Miller
Kathleen
K
O'Neil
Natasha M
NM
Ruth
Carol A
CA
Wallace
Nora G
NG
Singer
Christy I
CI
Sandborg
D000293:Adolescent; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D011993:Recombinant Fusion Proteins; C531377:rilonacept