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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/26186

Title: Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes
Authors: De Benedetti, F.
Gattorno, M.
Anton, J.
Ben-Chetrit, E.
Frenkel, J.
Hoffman, H. M.
Kone-Paut, I.
Lachmann, H. J.
Ozen, S.
Simon, A.
Zeft, A.
Penades, I. Calvo
Moutschen, M.
Quartier, P.
Kasapcopur, O.
Shcherbina, A.
Hofer, M.
Hashkes, P. J.
Van der Hilst, Jeroen
Hara, R.
Bujan-Rivas, S.
Constantin, Tamas
Gul, A.
Livneh, A.
Brogan, P.
Cattalini, M.
Obici, L.
Lheritier, K.
Speziale, A.
Junge, G.
Issue Date: 2018
Citation: NEW ENGLAND JOURNAL OF MEDICINE, 378(20), p. 1908-1919
Abstract: BACKGROUND Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyper-immunoglobulinemia 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<0.001), 35% versus 6% of those with mevalonate kinase deficiency (P = 0.003), and 45% versus 8% of those with TRAPS (P = 0.006). The inclusion of patients whose dose was increased to 300 mg every 4 weeks yielded a complete response in 71% of those with colchicine-resistant familial Mediterranean fever, 57% of those with mevalonate kinase deficiency, and 73% of those with TRAPS. After week 16, an extended dosing regimen (every 8 weeks) maintained disease control in 46% of patients with colchicine-resistant familial Mediterranean fever, 23% of those with mevalonate kinase deficiency, and 53% of those with TRAPS. Among patients who received canakinumab, the most frequently reported adverse events were infections (173.3, 313.5, and 148.0 per 100 patient-years among patients with colchicine-resistant familial Mediterranean fever, those with mevalonate kinase deficiency, and those with TRAPS, respectively), with a few being serious infections (6.6, 13.7, and 0.0 per 100 patient-years). CONCLUSIONS In this trial, canakinumab was effective in controlling and preventing flares in patients with colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, and TRAPS.
Notes: De Benedetti, F (reprint author), Osped Pediat Bambino Gesu, Div Rheumatol, Piazza S Onofrio 4, I-00186 Rome, Italy. fabrizio.debenedetti@opbg.net
URI: http://hdl.handle.net/1942/26186
DOI: 10.1056/NEJMoa1706314
ISI #: 000432299600008
ISSN: 0028-4793
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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