ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 14

Efficacy and Safety of Canakinumab in Patients with Periodic Fever Syndromes (Colchicine-Resistant FMF, HIDS/MKD and TRAPS): Results from a Phase 3, Pivotal, Umbrella Trial

Fabrizio De Benedetti1, Jordi Anton2, Eldad Ben-Chetrit3, Inmaculada Calvo4, Joost Frenkel5, Marco Gattorno6, Hal M. Hoffman7, Ozgur Kasapcopur8, Isabelle Koné-Paut9, Helen Lachmann10, Michel Moutschen11, Seza Ozen12, Pierre Quartier13, Anna Simon14, Andrew Zeft15, Karine Lheritier16, Antonio Speziale16 and Guido Junge16, 1IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, 2Unitat de Reumatologia Pediàtrica, Hospital Sant Joan de Déu, Barcelona, Spain, 3Rheumatology Unit, Hadassah—Hebrew University Medical Center, Jerusalem, Israel, 4Hospital Universitario y Polytecnico La Fe, Valencia, Spain, 5University Medical Center,Utrecht, Utrecht, Netherlands, 6Pediatric Rheumatology, G. Gaslini Institute, Genoa, Italy, 7Division of Rheumatology, Allergy, and Immunology, University of California at San Deigo, La Jolla, CA, 8Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey, 9Hopital Kremlin Bicetre, University of Paris SUD, Paris, France, 10UK National Amyloidosis Centre, University College London Medical School, London, United Kingdom, 11CHU de Liège/ University of Liège, Liège, Belgium, 12Department of Pediatrics, Hacettepe University, Ankara, Turkey, 13Necker-Enfants Malades Hospital, Paris, France, 14National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 15Pediatrics Rheumatology, Cleveland Clinic, Cleveland, OH, 16Novartis Pharma AG, Basel, Switzerland

Meeting: 2017 Pediatric Rheumatology Symposium

Keywords:

Session Information

Date: Thursday, May 18, 2017

Session Title: Clinical and Therapeutic Poster Breakout I

Session Type: Abstract Submissions

Session Time: 4:45PM-5:15PM

Background/Purpose:  Open-label studies have suggested the efficacy of canakinumab (CAN), a fully human, highly specific anti-IL-1β neutralizing monoclonal antibody, in colchicine-resistant-FMF (crFMF), hyper-immunoglobulin (Ig) D syndrome/mevalonate kinase deficiency (HIDS/MKD), and tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS).1-3 We report the efficacy and safety of CAN from the randomized treatment epoch of the Phase 3 pivotal study in patients (pts) with crFMF, HIDS/MKD or TRAPS.

Methods:  The study (NCT02059291) consists of 3 disease cohorts (crFMF, HIDS /MKD and TRAPS) and 4 study epochs: a screening epoch (E1) of up to 12 wks, a randomized treatment epoch (E2) of 16 wks, a randomized withdrawal epoch (E3) of 24 wks and an open-label treatment epoch (E4) of 72 wks. Pts (aged ≥2 years) with a flare during E1were randomized (1:1) in E2 to receive CAN or placebo (PBO). Primary objective was to demonstrate that CAN 150 mg (or 2 mg/kg for pts ≤40 kg) sc q4w is superior to PBO. Safety assessments included adverse events (AEs) and serious AEs(SAEs).

Results: Of 181 pts (crFMF, n=63; HIDS/MKD, n=72; TRAPS, n=46) randomized in E2, 6 discontinued the study (5 PBO; 1 CAN). In all 3 disease cohorts, the proportion of responders for the primary outcome at Wk 16 was significantly higher with CAN vs PBO. At Wk 16, a significantly higher proportion of pts achieved a physician’s global assessment (PGA) score <2, C-reactive protein (CRP) ≤10 mg/L and serum amyloid A (SAA) ≤10 mg/L in the CAN group vs PBO in all 3 cohorts. The most frequently affected system organ class across 3 cohorts was infections and infestations typically involving the upper respiratory tract. The incidence of SAEs was 8.6%, 4.7% and 11.8% in crFMF, TRAPS and HIDS/MKD cohorts, respectively.

Conclusion: These results demonstrated superior efficacy of canakinumab after a 16-week treatment period compared with placebo. The overall safety profile was not distinct from those reported in previous controlled studies.

References:

1. Brik R, et al. Ann Rheum Dis. 2013;72:75.
2. Arostegui J, et al. Ann Rheum Dis. 2015;74:401.
3. Lachmann H, et al. Ann Rheum Dis.2015;74:852.

 

Disclosure: F. De Benedetti, 2; J. Anton, 2,5; E. Ben-Chetrit, 5; I. Calvo, 2,8; J. Frenkel, 2; M. Gattorno, 2,5; H. M. Hoffman, 5,8; O. Kasapcopur, 8; I. Koné-Paut, 2,8; H. Lachmann, 5,8; M. Moutschen, None; S. Ozen, 8; P. Quartier, 2,5,8; A. Simon, 2,5; A. Zeft, 1,5; K. Lheritier, 1,3; A. Speziale, 3; G. Junge, 3.

To cite this abstract in AMA style:

De Benedetti F, Anton J, Ben-Chetrit E, Calvo I, Frenkel J, Gattorno M, Hoffman HM, Kasapcopur O, Koné-Paut I, Lachmann H, Moutschen M, Ozen S, Quartier P, Simon A, Zeft A, Lheritier K, Speziale A, Junge G. Efficacy and Safety of Canakinumab in Patients with Periodic Fever Syndromes (Colchicine-Resistant FMF, HIDS/MKD and TRAPS): Results from a Phase 3, Pivotal, Umbrella Trial [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 4). https://acrabstracts.org/abstract/efficacy-and-safety-of-canakinumab-in-patients-with-periodic-fever-syndromes-colchicine-resistant-fmf-hidsmkd-and-traps-results-from-a-phase-3-pivotal-umbrella-trial-2/. Accessed December 17, 2018.

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