PMID- 36106542
OWN - NLM
STAT- MEDLINE
DCOM- 20220916
LR  - 20220920
IS  - 0392-856X (Print)
IS  - 0392-856X (Linking)
VI  - 40
IP  - 8
DP  - 2022 Sep
TI  - A randomised, double-blind, placebo-controlled phase III trial on the efficacy 
      and safety of tocilizumab in patients with familial Mediterranean fever.
PG  - 1535-1542
LID - 10.55563/clinexprheumatol/fgx9vv [doi]
AB  - OBJECTIVES: To evaluate the efficacy and safety of tocilizumab (TCZ), an 
      interleukin 6 receptor monoclonal antibody, in a subset of Japanese patients with 
      familial Mediterranean fever (FMF). METHODS: We performed a double-blind, 
      randomised, parallel-group trial, followed by an open-label extension trial, in 
      patients with colchicine-resistant or -intolerant FMF (crFMF) (UMIN000028010). 
      Patients were randomly assigned (1:1) to receive TCZ (162 mg every week) or 
      placebo, administered subcutaneously, for 24 weeks. Rescue treatment was allowed 
      if the rescue criteria were met. The primary endpoint was the number of fever 
      attacks over the 24 weeks of treatment. Secondary endpoints included the 
      frequency of accompanying symptoms during attacks, serum CRP and SAA values, and 
      adverse events (AEs). The open-label extension study evaluated the long-term 
      safety and efficacy of TCZ in patients who had completed the preceding study 
      (UMIN000032557). RESULTS: We randomly assigned 23 patients to either TCZ (n=1) or 
      placebo (n=12). The TCZ-placebo rate ratios were 0.691 (95% confidence intervals 
      (CI), 0.189-2.531; p=0.577) for the fever attacks, based on the group rates per 
      week. The recurrence of attacks was significantly lower in the TCZ group (hazard 
      ratio = 0.457; 95% CI, 0.240-0.869). Fever attacks, accompanying symptoms, serum 
      CRP and SAA values were controlled in most of the patients who received long-term 
      TCZ. In these trials, the numbers and severity of AEs did not differ between 
      groups. CONCLUSIONS: Although a primary endpoint was not met in the preceding 
      trial, long-term administration of TCZ showed stable efficacy and safety for 
      patients with crFMF.
FAU - Koga, Tomohiro
AU  - Koga T
AD  - Department of Immunology and Rheumatology, Division of Advanced Preventive 
      Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 
      Nagasaki, and Centre for Bioinformatics and Molecular Medicine, Nagasaki 
      University Graduate School of Biomedical Sciences, Nagasaki, Japan. 
      tkoga@nagasaki-u.ac.jp.
FAU - Sato, Shuntaro
AU  - Sato S
AD  - Nagasaki University Hospital, Clinical Research Centre, Nagasaki, Japan.
FAU - Hagimori, Naoko
AU  - Hagimori N
AD  - Nagasaki University Hospital, Clinical Research Centre, Nagasaki, and 
      Translational Research Centre for Medical Innovation, Foundation for Biomedical 
      Research and Innovation at Kobe, Japan.
FAU - Yamamoto, Hiroshi
AU  - Yamamoto H
AD  - Nagasaki University Hospital, Clinical Research Centre, Nagasaki, Japan.
FAU - Ishimura, Masataka
AU  - Ishimura M
AD  - Department of Paediatrics, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Yasumi, Takahiro
AU  - Yasumi T
AD  - Department of Paediatrics, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan.
FAU - Kirino, Yohei
AU  - Kirino Y
AD  - Department of Stem Cell and Immune Regulation, Yokohama City University Graduate 
      School of Medicine, Yokohama, Japan.
FAU - Ikeda, Kei
AU  - Ikeda K
AD  - Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba 
      University, Chiba, Japan.
FAU - Yachie, Akihiro
AU  - Yachie A
AD  - Division of Medical Safety, Kanazawa University Hospital, Kanazawa, Japan.
FAU - Migita, Kiyoshi
AU  - Migita K
AD  - Department of Rheumatology, Fukushima Medical University School of Medicine, 
      Fukushima, Japan.
FAU - Kishida, Dai
AU  - Kishida D
AD  - Department of Medicine (Neurology & Rheumatology), Shinshu University School of 
      Medicine, Matsumoto, Japan.
FAU - Atsumi, Tatsuya
AU  - Atsumi T
AD  - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and 
      Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
FAU - Kawakami, Atsushi
AU  - Kawakami A
AD  - Department of Immunology and Rheumatology, Division of Advanced Preventive 
      Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 
      Nagasaki, Japan. atsushik@nagasaki-u.ac.jp.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20220914
PL  - Italy
TA  - Clin Exp Rheumatol
JT  - Clinical and experimental rheumatology
JID - 8308521
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - I031V2H011 (tocilizumab)
RN  - SML2Y3J35T (Colchicine)
SB  - IM
MH  - *Antibodies, Monoclonal, Humanized/adverse effects
MH  - Colchicine/adverse effects
MH  - *Familial Mediterranean Fever/diagnosis/drug therapy
MH  - Humans
MH  - Treatment Outcome
EDAT- 2022/09/16 06:00
MHDA- 2022/09/17 06:00
CRDT- 2022/09/15 05:03
PHST- 2022/01/08 00:00 [received]
PHST- 2022/05/26 00:00 [accepted]
PHST- 2022/09/15 05:03 [entrez]
PHST- 2022/09/16 06:00 [pubmed]
PHST- 2022/09/17 06:00 [medline]
AID - 18271 [pii]
AID - 10.55563/clinexprheumatol/fgx9vv [doi]
PST - ppublish
SO  - Clin Exp Rheumatol. 2022 Sep;40(8):1535-1542. doi: 
      10.55563/clinexprheumatol/fgx9vv. Epub 2022 Sep 14.