PMID- 32571870
OWN - NLM
STAT- MEDLINE
DCOM- 20201123
LR  - 20221210
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Print)
IS  - 0003-4967 (Linking)
VI  - 79
IP  - 10
DP  - 2020 Oct
TI  - Long-term efficacy and safety of canakinumab in patients with 
      colchicine-resistant familial Mediterranean fever: results from the randomised 
      phase III CLUSTER trial.
PG  - 1362-1369
LID - 10.1136/annrheumdis-2020-217419 [doi]
AB  - OBJECTIVES: To evaluate the long-term efficacy and safety of canakinumab to treat 
      patients with colchicine-resistant familial Mediterranean fever (crFMF) during 
      Epoch 4 (weeks 41 to 113) of the CLUSTER study. METHODS: Patients received 
      open-label canakinumab 150 or 300 mg, every 4 or 8 weeks during a 72-week period. 
      We evaluated disease activity every 8 weeks using the physician global assessment 
      (PGA) of disease activity, counting the number of flares, and measuring 
      concentrations of C reactive protein (CRP) and serum amyloid A (SAA). Safety was 
      studied by determination and classification of observed adverse events (AEs). We 
      analysed safety and efficacy separately in two subgroups of patients receiving a 
      cumulative dose of less than 2700 mg, or equal or more than 2700 mg. RESULTS: Of 
      the 61 patients that started the CLUSTER study, 60 entered Epoch 4 and 57 
      completed it. During the 72-week period, 35/60 (58.3%) patients experienced no 
      flares, and 23/60 (38.3%) had one flare, as compared with a median of 17.5 flares 
      per year reported at baseline. PGA scores indicated no disease activity for the 
      majority of patients throughout the study. Median CRP concentrations were always 
      lower than 10 mg/L, while median SAA concentrations remained over the limit of 
      normal (10 mg/L) but under the 30 mg/L threshold. No new or unexpected AEs were 
      reported. CONCLUSION: crFMF patients treated with canakinumab during 72 weeks 
      experienced a minimal incidence of flares and good control of clinical disease 
      activity, with no new safety concerns reported.
CI  - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Ozen, Seza
AU  - Ozen S
AUID- ORCID: 0000-0003-2883-7868
AD  - Department of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey 
      sezaozen@gmail.com.
FAU - Ben-Cherit, Eldad
AU  - Ben-Cherit E
AD  - Rheumatology Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
FAU - Foeldvari, Ivan
AU  - Foeldvari I
AD  - Pediatric Rheumatology, Hamburg Centre for Pediatric and Adolescent Rheumatology, 
      Hamburg, Germany.
FAU - Amarilyo, Gil
AU  - Amarilyo G
AUID- ORCID: 0000-0002-3888-429X
AD  - Pediatric Rheumatology Unit, Schneider Children's Medical Center of Israel, Petah 
      Tikva, Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Ozdogan, Huri
AU  - Ozdogan H
AD  - Department of Internal Medicine, Division of Rheumatology, University of 
      Istanbul-Cerrahpasa, Istanbul, Turkey.
FAU - Vanderschueren, Steven
AU  - Vanderschueren S
AD  - Clinical Department of General Internal Medicine, Research Department of 
      Immunology, Microbiology and Transplantation, Laboratory for Clinical Infectious 
      and Inflammatory Disorders, University Hospitals, Leuven, Belgium.
FAU - Marzan, Katherine
AU  - Marzan K
AD  - Pediatrics Keck School of Medicine of USC, Children's Hospital Los Angeles, Los 
      Angeles, California, USA.
FAU - Kahlenberg, J Michelle
AU  - Kahlenberg JM
AUID- ORCID: 0000-0002-4006-8945
AD  - Division of Rheumatology, Department of Internal Medicine, University of 
      Michigan, Ann Arbor, Michigan, USA.
FAU - Dekker, Elise
AU  - Dekker E
AD  - Immunology, Hepatology & Dermatology Franchise, Novartis Pharma AG, Basel, 
      Switzerland.
FAU - De Benedetti, Fabrizio
AU  - De Benedetti F
AD  - Division of Rheumatology, Ospedale Pediatrico Bambino Gesu, Roma, Italy.
FAU - Kone-Paut, Isabelle
AU  - Kone-Paut I
AUID- ORCID: 0000-0001-8939-5763
AD  - Universite de Paris Sud-Saclay, Le Kremlin Bicetre, France.
AD  - Pediatric Rheumatology and CEREMAIA, Centre Hospitalier Universitaire (CHU) de Le 
      Kremlin Bicetre, Le Kremlin Bicetre, France.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200622
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunosuppressive Agents)
RN  - 37CQ2C7X93 (canakinumab)
SB  - IM
CIN - Ann Rheum Dis. 2022 Dec;81(12):e257. PMID: 32988842
CIN - Ann Rheum Dis. 2022 Dec;81(12):e256. PMID: 32988847
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*therapeutic use
MH  - Familial Mediterranean Fever/*drug therapy
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Male
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC7509527
OTO - NOTNLM
OT  - autoimmune diseases
OT  - cytokines
OT  - familial mediterranean fever
OT  - treatment
COIS- Competing interests: SO has been a consultant for Novartis and Speaker's Bureau 
      for Sobi; EB-C has been a consultant for Novartis; IF has been an Advisor for 
      Novartis; GA has received research grants from Novartis; HO has no potential 
      conflict of interest; SV has no potential conflict of interest; KM has received 
      research grant from Novartis; JMK has been an Advisor for AstraZeneca, Bristol 
      Myers Squibb, Boehringer Ingleheim and Eli Lilly; JMK has received research 
      grants from Bristol Myers Squibb; ED is an employee of Novartis; FDB has received 
      research grants from Novartis, Sobi, Novimmune, Abbvie, Roche and Sanofi; IK-P 
      has been a consultant for Novartis, LBF, Sobi, CHUGAI, Pfizer and Abbvie; IK-P 
      has received research grant (non-financial) from Sobi.
EDAT- 2020/06/24 06:00
MHDA- 2020/11/24 06:00
PMCR- 2020/09/23
CRDT- 2020/06/24 06:00
PHST- 2020/03/25 00:00 [received]
PHST- 2020/05/28 00:00 [revised]
PHST- 2020/05/29 00:00 [accepted]
PHST- 2020/06/24 06:00 [pubmed]
PHST- 2020/11/24 06:00 [medline]
PHST- 2020/06/24 06:00 [entrez]
PHST- 2020/09/23 00:00 [pmc-release]
AID - annrheumdis-2020-217419 [pii]
AID - 10.1136/annrheumdis-2020-217419 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2020 Oct;79(10):1362-1369. doi: 10.1136/annrheumdis-2020-217419. 
      Epub 2020 Jun 22.