Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis

Nicolino Ruperto, Hermine I. Brunner, Pierre Quartier, Tamás Constantin, Nico Wulffraat, Gerd Horneff, Riva Brik, Liza McCann, Ozgur Kasapcopur, Lidia Rutkowska-Sak, Rayfel Schneider, Yackov Berkun, Inmaculada Calvo, Muferet Erguven, Laurence Goffin, Michael Hofer, Tilmann Kallinich, Sheila K. Oliveira, Yosef Uziel, Stefania ViolaKiran Nistala, Carine Wouters, Rolando Cimaz, Manuel A. Ferrandiz, Berit Flato, Maria Luz Gamir, Isabelle Kone-Paut, Alexei Grom, Bo Magnusson, Seza Ozen, Flavio Sztajnbok, Karine Lheritier, Ken Abrams, Dennis Kim, Alberto Martini, Daniel J. Lovell

Research output: Contribution to journalArticle

348 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)2396-2406
Number of pages11
JournalNew England Journal of Medicine
Volume367
Issue number25
DOIs
Publication statusPublished - Dec 20 2012

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Juvenile Arthritis
Placebos
Interleukin-1
Glucocorticoids
Fever
C-Reactive Protein
canakinumab
Joints
Monoclonal Antibodies
Body Weight
Safety
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ruperto, N., Brunner, H. I., Quartier, P., Constantin, T., Wulffraat, N., Horneff, G., ... Lovell, D. J. (2012). Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. New England Journal of Medicine, 367(25), 2396-2406. https://doi.org/10.1056/NEJMoa1205099

Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. / Ruperto, Nicolino; Brunner, Hermine I.; Quartier, Pierre; Constantin, Tamás; Wulffraat, Nico; Horneff, Gerd; Brik, Riva; McCann, Liza; Kasapcopur, Ozgur; Rutkowska-Sak, Lidia; Schneider, Rayfel; Berkun, Yackov; Calvo, Inmaculada; Erguven, Muferet; Goffin, Laurence; Hofer, Michael; Kallinich, Tilmann; Oliveira, Sheila K.; Uziel, Yosef; Viola, Stefania; Nistala, Kiran; Wouters, Carine; Cimaz, Rolando; Ferrandiz, Manuel A.; Flato, Berit; Gamir, Maria Luz; Kone-Paut, Isabelle; Grom, Alexei; Magnusson, Bo; Ozen, Seza; Sztajnbok, Flavio; Lheritier, Karine; Abrams, Ken; Kim, Dennis; Martini, Alberto; Lovell, Daniel J.

In: New England Journal of Medicine, Vol. 367, No. 25, 20.12.2012, p. 2396-2406.

Research output: Contribution to journalArticle

Ruperto, N, Brunner, HI, Quartier, P, Constantin, T, Wulffraat, N, Horneff, G, Brik, R, McCann, L, Kasapcopur, O, Rutkowska-Sak, L, Schneider, R, Berkun, Y, Calvo, I, Erguven, M, Goffin, L, Hofer, M, Kallinich, T, Oliveira, SK, Uziel, Y, Viola, S, Nistala, K, Wouters, C, Cimaz, R, Ferrandiz, MA, Flato, B, Gamir, ML, Kone-Paut, I, Grom, A, Magnusson, B, Ozen, S, Sztajnbok, F, Lheritier, K, Abrams, K, Kim, D, Martini, A & Lovell, DJ 2012, 'Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis', New England Journal of Medicine, vol. 367, no. 25, pp. 2396-2406. https://doi.org/10.1056/NEJMoa1205099
Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. New England Journal of Medicine. 2012 Dec 20;367(25):2396-2406. https://doi.org/10.1056/NEJMoa1205099
Ruperto, Nicolino ; Brunner, Hermine I. ; Quartier, Pierre ; Constantin, Tamás ; Wulffraat, Nico ; Horneff, Gerd ; Brik, Riva ; McCann, Liza ; Kasapcopur, Ozgur ; Rutkowska-Sak, Lidia ; Schneider, Rayfel ; Berkun, Yackov ; Calvo, Inmaculada ; Erguven, Muferet ; Goffin, Laurence ; Hofer, Michael ; Kallinich, Tilmann ; Oliveira, Sheila K. ; Uziel, Yosef ; Viola, Stefania ; Nistala, Kiran ; Wouters, Carine ; Cimaz, Rolando ; Ferrandiz, Manuel A. ; Flato, Berit ; Gamir, Maria Luz ; Kone-Paut, Isabelle ; Grom, Alexei ; Magnusson, Bo ; Ozen, Seza ; Sztajnbok, Flavio ; Lheritier, Karine ; Abrams, Ken ; Kim, Dennis ; Martini, Alberto ; Lovell, Daniel J. / Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. In: New England Journal of Medicine. 2012 ; Vol. 367, No. 25. pp. 2396-2406.
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abstract = "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",
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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

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