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OP0063 Canakinumab treatment in patients with colchicine-resistant FMF (CRFMF), HIDS/MKD and traps: efficacy in the 16 weeks randomised controlled phase and maintenance of disease control and safety at week 40
  1. F De Benedetti1,
  2. M Gattorno2,
  3. J Frenkel3,
  4. I Calvo4,
  5. M Moutschen5,
  6. P Quartier6,
  7. O Kasapcopur7,
  8. S Ozen8,
  9. A Gül9,
  10. J Anton10,
  11. I Koné-Paut11,
  12. H Lachmann12,
  13. HM Hoffman13,
  14. E Ben-Chetrit14,
  15. A Zeft15,
  16. Y Gong16,
  17. E Vritzali17,
  18. G Junge17
  1. 1IRCCS Ospedale Pediatrico Bambino Gesú, Rome
  2. 2G. Gaslini Institute, Genoa, Italy
  3. 3University Medical Center, Utrecht, Netherlands
  4. 4Hospital Universitario i Politecnic la Fe, Valencia, Spain
  5. 5CHU de Liège/University of Liège, Liège, Belgium
  6. 6Necker-Enfants Malades Hospital, Paris, France
  7. 7Department of Pediatric Rheumatology, Istanbul University Cerrahpasa Medical Faculty, Istanbul
  8. 8Hacettepe University, Ankara
  9. 9Department of Internal Medicine, Rheumatology Division, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
  10. 10Hospital Sant Joan de Déu, Barcelona, Spain
  11. 11Hôpital Kremlin Bicetre, Paris, France
  12. 12UK National Amyloidosis Centre, London, United Kingdom
  13. 13University of California, la Jolla, United States
  14. 14Rheumatology Unit, Hadassah–Hebrew University Medical Center, Jerusalem, Israel
  15. 15Pediatrics Rheumatology, Cleveland Clinic, Cleveland, United States
  16. 16Novartis Pharma, Shanghai, China
  17. 17Novartis Pharma AG, Basel, Switzerland


Background Canakinumab (CAN) is a fully human monoclonal antibody targeting IL-1β, a key cytokine in the pathogenesis of periodic fever syndromes (PFS) including familial Mediterranean fever (FMF), hyper-IgD syndrome/mevalonate kinase deficiency (HIDS/MKD) and TNF receptor-associated periodic syndrome (TRAPS).

Objectives The CLUSTER trial (NCT02059291) studied efficacy and safety of CAN in crFMF, HIDS/MKD and TRAPS. The primary objective was to demonstrate that CAN150 mg every 4 weeks (q4w) is superior to placebo (PBO) in resolving the flare by Day 15 with no new flares over 16 weeks (wks). Secondary objectives included the proportion of patients (pts) who maintained optimal control of disease activity (absence of new flares) between Wk 16 and Wk 40 after dose reduction.

Methods The study comprised 4 epochs (E1-E4).1 After lead-in E1, in E2 patients at time of an active fever flare were randomised to CAN 150mg q4w or PBO for 16 wks. Responders in E2 were re-randomised to PBO or 150 mg q8w for 24 wks. During E3, pts who escaped to open-label CAN in E2, were similarly down-titrated to open-label CAN q8w to gain additional information on the long-term maintenance dose. In pts with a flare, dose could be escalated up to 300 mg q4w. Safety assessments included adverse events (AEs) and serious AEs.

Results The proportion of responders at Wk 16 was statistically higher with CAN vs PBO (Table). In E3, among the 41 re-randomised pts (PBO vs CAN 150 mg q8w) the proportion of pts who did not present new flares was numerically higher in the CAN vs PBO group (Table). Overall at Wk 40 (end of E3), including re-randomised pts and pts treated in open-label, 46% of the crFMF pts, 53% of the TRAPS pts and 23% of the HIDS/MKD pts maintained disease control with 150 mg q8w. Conversely, up-titration to 300 mg q4w was required in 28.8% of HIDS/MKD pts, and in 10.2% and 8.3% of pts with crFMF and TRAPS, respectively. In E3, the majority of pts who received CAN had PGA <2, normal CRP and SAA levels in all 3 cohorts. No new safety findings nor death were reported in CAN-treated pts through E3 (Table).

Conclusions Canakinumab (150 mg q4w) was efficacious in resolving flare at Day 15 and preventing new flares over 16 wks. In the longer term (40 wks), absence of flares was maintained in more than half patients at the extended dosing interval (150 mg q8w) in the crFMF and TRAPS cohorts. A higher dose was needed in HIDS/MKD patients. No unexpected safety issues were reported over 40 wks of canakinumab treatment.


  1. De Benedetti F, et al. Ann Rheum Dis. 2016;75:615–6.


Disclosure of Interest F. De Benedetti Grant/research support from: Pfizer, AbbVie, Roche, Novartis, Novimmune and BMS, M. Gattorno Grant/research support from: Novartis and SOBI, Consultant for: Novartis and SOBI, J. Frenkel Grant/research support from: Novartis and SOBI, I. Calvo Grant/research support from: Novartis, Pfizer, AbbVie and Roche, Speakers bureau: Novartis, AbbVie, Gebro and Roche, M. Moutschen: None declared, P. Quartier Grant/research support from: AbbVie, BMS, Chugai-Roche, Novartis and Pfizer, Consultant for: AbbVie, Novartis, Servier and SOBI, Speakers bureau: AbbVie, BMS, Chugai-Roche, Medimmune, Novartis, Pfizer and SOBI, O. Kasapcopur Consultant for: Novartis, Speakers bureau: Novartis and Pfizer, S. Ozen Speakers bureau: Novartis and SOBI, A. Gül Grant/research support from: Novartis, J. Anton Grant/research support from: Novartis, Consultant for: Novartis, I. Koné-Paut Grant/research support from: Novartis, SOBI and Roche, Consultant for: Novartis, SOBI, Pfizer, AbbVie and Roche, H. Lachmann Consultant for: Novartis, SOBI, Takeda and GSK, Speakers bureau: Novartis and SOBI, H. Hoffman Consultant for: Novartis, Speakers bureau: Novartis, E. Ben-Chetrit Consultant for: Novartis, A. Zeft Shareholder of: Merck, Opko Health and Arno therapeutics, Consultant for: Novartis, Y. Gong Employee of: Novartis, E. Vritzali Employee of: Novartis, G. Junge Employee of: Novartis

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