Canakinumab for the treatment of autoinflammatory recurrent fever syndromes

Fabrizio De Benedetti, Marco Gattorno, Jordi Anton, Ben Chetrit Eldad, Joost Frenkel, Hal M. Hoffman, Koné Paut Isabelle, Helen J. Lachmann, Seza Ozen, Anna Simon, Andrew Zeft, Inmaculada Calvo Penades, Michel Moutschen, Pierre Quartier, Ozgur Kasapcopur, Anna Shcherbina, Michael Hofer, Philip J. Hashkes, Jeroen Van der Hilst, Ryoki HaraBujan Rivas Segundo, Tamas Constantin, Ahmet Gul, Avi Livneh, Paul Brogan, Marco Cattalini, Laura Obici, Karine Lheritier, Antonio Speziale, Guido Junge

Research output: Contribution to journalArticle

Abstract

BACKGROUND Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor–associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares. METHODS We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. The primary outcome was complete response (resolution of flare and no flare until week 16). In the subsequent phase up to week 40, patients who had a complete response underwent a second randomization to receive canakinumab or placebo every 8 weeks. Patients who underwent a second randomization and had a subsequent flare and all other patients received open-label canakinumab. RESULTS At week 16, significantly more patients receiving canakinumab had a complete response than those receiving placebo: 61% vs. 6% of patients with colchicine-resistant familial Mediterranean fever (P
Original languageEnglish
Pages (from-to)1908-1919
Number of pages12
JournalNew England Journal of Medicine
Volume378
Issue number20
DOIs
Publication statusPublished - May 17 2018

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Fever
Mevalonate Kinase Deficiency
Familial Mediterranean Fever
Placebos
Colchicine
Random Allocation
Therapeutics
canakinumab
Tumor Necrosis Factor-alpha
Injections

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Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. / De Benedetti, Fabrizio; Gattorno, Marco; Anton, Jordi; Eldad, Ben Chetrit; Frenkel, Joost; Hoffman, Hal M.; Isabelle, Koné Paut; Lachmann, Helen J.; Ozen, Seza; Simon, Anna; Zeft, Andrew; Penades, Inmaculada Calvo; Moutschen, Michel; Quartier, Pierre; Kasapcopur, Ozgur; Shcherbina, Anna; Hofer, Michael; Hashkes, Philip J.; Van der Hilst, Jeroen; Hara, Ryoki; Segundo, Bujan Rivas; Constantin, Tamas; Gul, Ahmet; Livneh, Avi; Brogan, Paul; Cattalini, Marco; Obici, Laura; Lheritier, Karine; Speziale, Antonio; Junge, Guido.

In: New England Journal of Medicine, Vol. 378, No. 20, 17.05.2018, p. 1908-1919.

Research output: Contribution to journalArticle

De Benedetti, F, Gattorno, M, Anton, J, Eldad, BC, Frenkel, J, Hoffman, HM, Isabelle, KP, Lachmann, HJ, Ozen, S, Simon, A, Zeft, A, Penades, IC, Moutschen, M, Quartier, P, Kasapcopur, O, Shcherbina, A, Hofer, M, Hashkes, PJ, Van der Hilst, J, Hara, R, Segundo, BR, Constantin, T, Gul, A, Livneh, A, Brogan, P, Cattalini, M, Obici, L, Lheritier, K, Speziale, A & Junge, G 2018, 'Canakinumab for the treatment of autoinflammatory recurrent fever syndromes', New England Journal of Medicine, vol. 378, no. 20, pp. 1908-1919. https://doi.org/10.1056/NEJMoa1706314
De Benedetti, Fabrizio ; Gattorno, Marco ; Anton, Jordi ; Eldad, Ben Chetrit ; Frenkel, Joost ; Hoffman, Hal M. ; Isabelle, Koné Paut ; Lachmann, Helen J. ; Ozen, Seza ; Simon, Anna ; Zeft, Andrew ; Penades, Inmaculada Calvo ; Moutschen, Michel ; Quartier, Pierre ; Kasapcopur, Ozgur ; Shcherbina, Anna ; Hofer, Michael ; Hashkes, Philip J. ; Van der Hilst, Jeroen ; Hara, Ryoki ; Segundo, Bujan Rivas ; Constantin, Tamas ; Gul, Ahmet ; Livneh, Avi ; Brogan, Paul ; Cattalini, Marco ; Obici, Laura ; Lheritier, Karine ; Speziale, Antonio ; Junge, Guido. / Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. In: New England Journal of Medicine. 2018 ; Vol. 378, No. 20. pp. 1908-1919.
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abstract = "BACKGROUND Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor–associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares. METHODS We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. The primary outcome was complete response (resolution of flare and no flare until week 16). In the subsequent phase up to week 40, patients who had a complete response underwent a second randomization to receive canakinumab or placebo every 8 weeks. Patients who underwent a second randomization and had a subsequent flare and all other patients received open-label canakinumab. RESULTS At week 16, significantly more patients receiving canakinumab had a complete response than those receiving placebo: 61{\%} vs. 6{\%} of patients with colchicine-resistant familial Mediterranean fever (P",
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AU - De Benedetti, Fabrizio

AU - Gattorno, Marco

AU - Anton, Jordi

AU - Eldad, Ben Chetrit

AU - Frenkel, Joost

AU - Hoffman, Hal M.

AU - Isabelle, Koné Paut

AU - Lachmann, Helen J.

AU - Ozen, Seza

AU - Simon, Anna

AU - Zeft, Andrew

AU - Penades, Inmaculada Calvo

AU - Moutschen, Michel

AU - Quartier, Pierre

AU - Kasapcopur, Ozgur

AU - Shcherbina, Anna

AU - Hofer, Michael

AU - Hashkes, Philip J.

AU - Van der Hilst, Jeroen

AU - Hara, Ryoki

AU - Segundo, Bujan Rivas

AU - Constantin, Tamas

AU - Gul, Ahmet

AU - Livneh, Avi

AU - Brogan, Paul

AU - Cattalini, Marco

AU - Obici, Laura

AU - Lheritier, Karine

AU - Speziale, Antonio

AU - Junge, Guido

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N2 - BACKGROUND Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor–associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares. METHODS We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. The primary outcome was complete response (resolution of flare and no flare until week 16). In the subsequent phase up to week 40, patients who had a complete response underwent a second randomization to receive canakinumab or placebo every 8 weeks. Patients who underwent a second randomization and had a subsequent flare and all other patients received open-label canakinumab. RESULTS At week 16, significantly more patients receiving canakinumab had a complete response than those receiving placebo: 61% vs. 6% of patients with colchicine-resistant familial Mediterranean fever (P

AB - BACKGROUND Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor–associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares. METHODS We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. The primary outcome was complete response (resolution of flare and no flare until week 16). In the subsequent phase up to week 40, patients who had a complete response underwent a second randomization to receive canakinumab or placebo every 8 weeks. Patients who underwent a second randomization and had a subsequent flare and all other patients received open-label canakinumab. RESULTS At week 16, significantly more patients receiving canakinumab had a complete response than those receiving placebo: 61% vs. 6% of patients with colchicine-resistant familial Mediterranean fever (P

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