Titre
Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Ruperto, N.
Auteure/Auteur
Brunner, H.I.
Auteure/Auteur
Quartier, P.
Auteure/Auteur
Constantin, T.
Auteure/Auteur
Wulffraat, N.
Auteure/Auteur
Horneff, G.
Auteure/Auteur
Brik, R.
Auteure/Auteur
McCann, L.
Auteure/Auteur
Kasapcopur, O.
Auteure/Auteur
Rutkowska-Sak, L.
Auteure/Auteur
Schneider, R.
Auteure/Auteur
Berkun, Y.
Auteure/Auteur
Calvo, I.
Auteure/Auteur
Erguven, M.
Auteure/Auteur
Goffin, L.
Auteure/Auteur
Hofer, M.
Auteure/Auteur
Kallinich, T.
Auteure/Auteur
Oliveira, S.K.
Auteure/Auteur
Uziel, Y.
Auteure/Auteur
Viola, S.
Auteure/Auteur
Nistala, K.
Auteure/Auteur
Wouters, C.
Auteure/Auteur
Cimaz, R.
Auteure/Auteur
Ferrandiz, M.A.
Auteure/Auteur
Flato, B.
Auteure/Auteur
Gamir, M.L.
Auteure/Auteur
Kone-Paut, I.
Auteure/Auteur
Grom, A.
Auteure/Auteur
Magnusson, B.
Auteure/Auteur
Ozen, S.
Auteure/Auteur
Sztajnbok, F.
Auteure/Auteur
Lheritier, K.
Auteure/Auteur
Abrams, K.
Auteure/Auteur
Kim, D.
Auteure/Auteur
Martini, A.
Auteure/Auteur
Lovell, D.J.
Auteure/Auteur
PRINTO,
Auteure/Auteur
PRCSG,
Auteure/Auteur
Contributrices/contributeurs
PRINTO,
PRCSG,
Cuttica, R.
Emminger, W.
Lauwerys, B.
Joos, R.
Goffin, L.
Wouters, C.
Bandeira, M.
Sztajnbok, F.
Knupp, S.
Len, C.
Kone-Paut, I.
Quartier, P.
Desjonqueres, M.
Fischbach, M.
Kallinich, T.
Berner, R.
Thon, A.
Frosch, M.
Horneff, G.
Trauzeddel, R.
Weissbarth-Riedel, E.
Trachana, M.
Constantin£££Tamás£££ T.,
Brik, R.
Uziel, Y.
Berkun, Y.
Barash, J.
Harel, L.
Cimaz, R.
Viola, S.
Corona, F.
Gerloni, V.
Alessio, M.
Wulffraat, NM.
Flato, B.
Ferrandiz, M.
Rutkowska-Sak, L.
Anton, J.
Calvo, I.
Gamir, ML.
Robledillo, JC.
Magnusson, B.
Hofer, M.
Ozen, S.
Ozdogan, H.
Erguven, M.
Unsal, E.
McCann, L.
Woo, P.
Foster, H.
Ramanan, A.
Chieng, A.
Wilkinson, N.
Schneider, R.
Houghton, K.
Tucker, L.
Haddad, E.
Lopez-Benitez, J.
Lovell, D.
Morris, P.
Schikler, K.
Kingsbury, D.
Higgins, G.
Marzan, K.
Cuttica, R.
Emminger, W.
Joos, R.
Lauwerys, B.
Hilario, M.
Radominski, S.
Haddad, E.
Houghton, K.
Bader-Meunier, B.
Desjonqueres, M.
Fischbach, M.
Marie, I.
Mogenet, A.
Mouy, R.
Berner, R.
Frosch, M.
Thon, A.
Trauzeddel, R.
Weibarth-Riedel, E.
Trachana, M.
Barash, J.
Harel, L.
Alessio, M.
Corona, F.
Gerloni, V.
Anton, J.
Robledillos, JC.
Unsal, E.
Chieng, A.
Foster, H.
Ramanan, A.
Wilkinson, N.
Miller, J.
Higgins, G.
Kingsbury, D.
Lopez-Benitez, J.
Marzan, K.
Morris, P.
Schikler, K.
Liens vers les personnes
Liens vers les unités
ISSN
1533-4406
Statut éditorial
Publié
Date de publication
2012
Volume
367
Numéro
25
Première page
2396
Dernière page/numéro d’article
2406
Langue
anglais
Notes
Publication types: Clinical Trial, Phase III ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
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.).
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.).
Sujets
PID Serval
serval:BIB_BB127A32232C
PMID
Date de création
2013-01-04T10:08:04.837Z
Date de création dans IRIS
2025-05-21T04:53:28Z