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A randomised, double-blind, placebo-controlled phase III trial on the efficacy and safety of tocilizumab in patients with familial Mediterranean fever
T. Koga1, S. Sato2, N. Hagimori3, H. Yamamoto4, M. Ishimura5, T. Yasumi6, Y. Kirino7, K. Ikeda8, A. Yachie9, K. Migita10, D. Kishida11, T. Atsumi12, A. Kawakami13
- 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
- Nagasaki University Hospital, Clinical Research Centre, Nagasaki, Japan.
- Nagasaki University Hospital, Clinical Research Centre, Nagasaki, and Translational Research Centre for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Japan.
- Nagasaki University Hospital, Clinical Research Centre, Nagasaki, Japan.
- Department of Paediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
- Department of Paediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
- Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
- Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
- Division of Medical Safety, Kanazawa University Hospital, Kanazawa, Japan.
- Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
- Department of Medicine (Neurology & Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan.
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
- 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
CER15467
2022 Vol.40, N°8
PI 1535, PF 1542
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PMID: 36106542 [PubMed]
Received: 08/01/2022
Accepted : 26/05/2022
In Press: 14/09/2022
Published: 14/09/2022
Abstract
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.
