TY - JOUR
T1 - Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis
AU - Ruperto, Nicolino
AU - Brunner, Hermine I.
AU - Quartier, Pierre
AU - Constantin, Tamás
AU - Wulffraat, Nico
AU - Horneff, Gerd
AU - Brik, Riva
AU - McCann, Liza
AU - Kasapcopur, Ozgur
AU - Rutkowska-Sak, Lidia
AU - Schneider, Rayfel
AU - Berkun, Yackov
AU - Calvo, Inmaculada
AU - Erguven, Muferet
AU - Goffin, Laurence
AU - Hofer, Michael
AU - Kallinich, Tilmann
AU - Oliveira, Sheila K.
AU - Uziel, Yosef
AU - Viola, Stefania
AU - Nistala, Kiran
AU - Wouters, Carine
AU - Cimaz, Rolando
AU - Ferrandiz, Manuel A.
AU - Flato, Berit
AU - Gamir, Maria Luz
AU - Kone-Paut, Isabelle
AU - Grom, Alexei
AU - Magnusson, Bo
AU - Ozen, Seza
AU - Sztajnbok, Flavio
AU - Lheritier, Karine
AU - Abrams, Ken
AU - Kim, Dennis
AU - Martini, Alberto
AU - Lovell, Daniel J.
PY - 2012/12/20
Y1 - 2012/12/20
N2 - BACKGROUND: Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1β monoclonal antibody, in two trials. METHODS:In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilogram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, patients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. RESULTS: At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to placebo (74% of patients in the canakinumab group had no flare, vs. 25% in the placebo group, according to Kaplan-Meier estimates; hazard ratio, 0.36; P = 0.003). The average glucocorticoid dose was reduced from 0.34 to 0.05 mg per kilogram per day, and glucocorticoids were discontinued in 42 of 128 patients (33%). The macrophage activation syndrome occurred in 7 patients; infections were more frequent with canakinumab than with placebo. CONCLUSIONS: These two phase 3 studies show the efficacy of canakinumab in systemic JIA with active systemic features. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT00889863 and NCT00886769.)
AB - BACKGROUND: Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1β monoclonal antibody, in two trials. METHODS:In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilogram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, patients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. RESULTS: At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to placebo (74% of patients in the canakinumab group had no flare, vs. 25% in the placebo group, according to Kaplan-Meier estimates; hazard ratio, 0.36; P = 0.003). The average glucocorticoid dose was reduced from 0.34 to 0.05 mg per kilogram per day, and glucocorticoids were discontinued in 42 of 128 patients (33%). The macrophage activation syndrome occurred in 7 patients; infections were more frequent with canakinumab than with placebo. CONCLUSIONS: These two phase 3 studies show the efficacy of canakinumab in systemic JIA with active systemic features. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT00889863 and NCT00886769.)
UR - http://www.scopus.com/inward/record.url?scp=84871321221&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1205099
DO - 10.1056/NEJMoa1205099
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C2 - 23252526
AN - SCOPUS:84871321221
SN - 0028-4793
VL - 367
SP - 2396
EP - 2406
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 25
ER -