Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features

Results from the 5-year long-term extension of the phase III pivotal trials

Nicolino Ruperto, Hermine I. Brunner, Pierre Quartier, T. Constantin, Nico M. Wulffraat, Gerd Horneff, Ozgur Kasapcopur, Rayfel Schneider, Jordi Anton, Judith Barash, Reinhard Berner, Fabrizia Corona, Ruben Cuttica, Marine Fouillet-Desjonqueres, Michel Fischbach, Helen E. Foster, Dirk Foell, Sebastião C. Radominski, Athimalaipet V. Ramanan, Ralf Trauzeddel & 5 others Erbil Unsal, Jérémy Levy, Eleni Vritzali, Alberto Martini, Daniel J. Lovell

Research output: Article

8 Citations (Scopus)

Abstract

Objectives: To evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA). Methods: Patients (2-19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CRACR). Efficacy analyses are reported as per the intent-to-treat population. Results: 144 of the 177 patients (81%) enrolled in the core study entered the LTE. Overall, 75 patients (42%) completed and 102 (58%) discontinued mainly for inefficacy (63/102, 62%), with higher discontinuation rates noted in the late responders group (n=25/31, 81%) versus early responders (n=11/38, 29%). At 2 years, aJIA-ACR 50/70/90 response rates were 62%, 61% and 54%, respectively. CRACR was achieved by 20% of patients at month 6; 32% at 2 years. A JADAS low disease activity score was achieved by 49% of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3%) patients on glucocorticoids, 20 (15.6%) discontinued and 28 (22%) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed. Conclusion: Response to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab. Trial registration numbers: NCT00886769, NCT00889863, NCT00426218 and NCT00891046.

Original languageEnglish
JournalAnnals of the Rheumatic Diseases
DOIs
Publication statusAccepted/In press - jan. 1 2018

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Juvenile Arthritis
Glucocorticoids
Macrophages
Safety
Macrophage Activation Syndrome
Chemical activation
canakinumab
Rheumatology
Therapeutics

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features : Results from the 5-year long-term extension of the phase III pivotal trials. / Ruperto, Nicolino; Brunner, Hermine I.; Quartier, Pierre; Constantin, T.; Wulffraat, Nico M.; Horneff, Gerd; Kasapcopur, Ozgur; Schneider, Rayfel; Anton, Jordi; Barash, Judith; Berner, Reinhard; Corona, Fabrizia; Cuttica, Ruben; Fouillet-Desjonqueres, Marine; Fischbach, Michel; Foster, Helen E.; Foell, Dirk; Radominski, Sebastião C.; Ramanan, Athimalaipet V.; Trauzeddel, Ralf; Unsal, Erbil; Levy, Jérémy; Vritzali, Eleni; Martini, Alberto; Lovell, Daniel J.

In: Annals of the Rheumatic Diseases, 01.01.2018.

Research output: Article

Ruperto, N, Brunner, HI, Quartier, P, Constantin, T, Wulffraat, NM, Horneff, G, Kasapcopur, O, Schneider, R, Anton, J, Barash, J, Berner, R, Corona, F, Cuttica, R, Fouillet-Desjonqueres, M, Fischbach, M, Foster, HE, Foell, D, Radominski, SC, Ramanan, AV, Trauzeddel, R, Unsal, E, Levy, J, Vritzali, E, Martini, A & Lovell, DJ 2018, 'Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: Results from the 5-year long-term extension of the phase III pivotal trials', Annals of the Rheumatic Diseases. https://doi.org/10.1136/annrheumdis-2018-213150
Ruperto, Nicolino ; Brunner, Hermine I. ; Quartier, Pierre ; Constantin, T. ; Wulffraat, Nico M. ; Horneff, Gerd ; Kasapcopur, Ozgur ; Schneider, Rayfel ; Anton, Jordi ; Barash, Judith ; Berner, Reinhard ; Corona, Fabrizia ; Cuttica, Ruben ; Fouillet-Desjonqueres, Marine ; Fischbach, Michel ; Foster, Helen E. ; Foell, Dirk ; Radominski, Sebastião C. ; Ramanan, Athimalaipet V. ; Trauzeddel, Ralf ; Unsal, Erbil ; Levy, Jérémy ; Vritzali, Eleni ; Martini, Alberto ; Lovell, Daniel J. / Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features : Results from the 5-year long-term extension of the phase III pivotal trials. In: Annals of the Rheumatic Diseases. 2018.
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abstract = "Objectives: To evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA). Methods: Patients (2-19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CRACR). Efficacy analyses are reported as per the intent-to-treat population. Results: 144 of the 177 patients (81{\%}) enrolled in the core study entered the LTE. Overall, 75 patients (42{\%}) completed and 102 (58{\%}) discontinued mainly for inefficacy (63/102, 62{\%}), with higher discontinuation rates noted in the late responders group (n=25/31, 81{\%}) versus early responders (n=11/38, 29{\%}). At 2 years, aJIA-ACR 50/70/90 response rates were 62{\%}, 61{\%} and 54{\%}, respectively. CRACR was achieved by 20{\%} of patients at month 6; 32{\%} at 2 years. A JADAS low disease activity score was achieved by 49{\%} of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3{\%}) patients on glucocorticoids, 20 (15.6{\%}) discontinued and 28 (22{\%}) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed. Conclusion: Response to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab. Trial registration numbers: NCT00886769, NCT00889863, NCT00426218 and NCT00891046.",
keywords = "canakinumab, clinical trial, interleukin-1β, long-term extension, systemic juvenile idiopathic arthritis.",
author = "Nicolino Ruperto and Brunner, {Hermine I.} and Pierre Quartier and T. Constantin and Wulffraat, {Nico M.} and Gerd Horneff and Ozgur Kasapcopur and Rayfel Schneider and Jordi Anton and Judith Barash and Reinhard Berner and Fabrizia Corona and Ruben Cuttica and Marine Fouillet-Desjonqueres and Michel Fischbach and Foster, {Helen E.} and Dirk Foell and Radominski, {Sebasti{\~a}o C.} and Ramanan, {Athimalaipet V.} and Ralf Trauzeddel and Erbil Unsal and J{\'e}r{\'e}my Levy and Eleni Vritzali and Alberto Martini and Lovell, {Daniel J.}",
year = "2018",
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language = "English",
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TY - JOUR

T1 - Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features

T2 - Results from the 5-year long-term extension of the phase III pivotal trials

AU - Ruperto, Nicolino

AU - Brunner, Hermine I.

AU - Quartier, Pierre

AU - Constantin, T.

AU - Wulffraat, Nico M.

AU - Horneff, Gerd

AU - Kasapcopur, Ozgur

AU - Schneider, Rayfel

AU - Anton, Jordi

AU - Barash, Judith

AU - Berner, Reinhard

AU - Corona, Fabrizia

AU - Cuttica, Ruben

AU - Fouillet-Desjonqueres, Marine

AU - Fischbach, Michel

AU - Foster, Helen E.

AU - Foell, Dirk

AU - Radominski, Sebastião C.

AU - Ramanan, Athimalaipet V.

AU - Trauzeddel, Ralf

AU - Unsal, Erbil

AU - Levy, Jérémy

AU - Vritzali, Eleni

AU - Martini, Alberto

AU - Lovell, Daniel J.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objectives: To evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA). Methods: Patients (2-19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CRACR). Efficacy analyses are reported as per the intent-to-treat population. Results: 144 of the 177 patients (81%) enrolled in the core study entered the LTE. Overall, 75 patients (42%) completed and 102 (58%) discontinued mainly for inefficacy (63/102, 62%), with higher discontinuation rates noted in the late responders group (n=25/31, 81%) versus early responders (n=11/38, 29%). At 2 years, aJIA-ACR 50/70/90 response rates were 62%, 61% and 54%, respectively. CRACR was achieved by 20% of patients at month 6; 32% at 2 years. A JADAS low disease activity score was achieved by 49% of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3%) patients on glucocorticoids, 20 (15.6%) discontinued and 28 (22%) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed. Conclusion: Response to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab. Trial registration numbers: NCT00886769, NCT00889863, NCT00426218 and NCT00891046.

AB - Objectives: To evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA). Methods: Patients (2-19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CRACR). Efficacy analyses are reported as per the intent-to-treat population. Results: 144 of the 177 patients (81%) enrolled in the core study entered the LTE. Overall, 75 patients (42%) completed and 102 (58%) discontinued mainly for inefficacy (63/102, 62%), with higher discontinuation rates noted in the late responders group (n=25/31, 81%) versus early responders (n=11/38, 29%). At 2 years, aJIA-ACR 50/70/90 response rates were 62%, 61% and 54%, respectively. CRACR was achieved by 20% of patients at month 6; 32% at 2 years. A JADAS low disease activity score was achieved by 49% of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3%) patients on glucocorticoids, 20 (15.6%) discontinued and 28 (22%) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed. Conclusion: Response to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab. Trial registration numbers: NCT00886769, NCT00889863, NCT00426218 and NCT00891046.

KW - canakinumab

KW - clinical trial

KW - interleukin-1β

KW - long-term extension

KW - systemic juvenile idiopathic arthritis.

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U2 - 10.1136/annrheumdis-2018-213150

DO - 10.1136/annrheumdis-2018-213150

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JO - Annals of the Rheumatic Diseases

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