Objective To evaluate the efficacy and safety of tocilizumab, an interleukin-6 receptor antibody, in patients with adult-onset Still’s disease.
Methods In this double-blind, randomised, placebo-controlled phase III trial, 27 patients with adult-onset Still’s disease refractory to glucocorticoids were randomised to tocilizumab at a dose of 8 mg/kg or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients received open-label tocilizumab for 40 weeks subsequently. The primary outcome was American College of Rheumatology (ACR) 50 response at week 4. The secondary outcomes included ACR 20/50/70, systemic feature score, glucocorticoid dose and adverse events at each point.
Results In the full analysis set, ACR50 response at week 4 was achieved in 61.5% (95% CI 31.6 to 86.1) in the tocilizumab group and 30.8% (95% CI 9.1 to 61.4) in the placebo group (p=0.24). The least squares means for change in systemic feature score at week 12 were –4.1 in the tocilizumab group and –2.3 in the placebo group (p=0.003). The dose of glucocorticoids at week 12 decreased by 46.2% in the tocilizumab group and 21.0% in the placebo group (p=0.017). At week 52, the rates of ACR20, ACR50 and ACR70 were 84.6%, 84.6% and 61.5%, respectively, in both groups. Serious adverse events in all participants who received one dose of tocilizumab were infections, aseptic necrosis in the hips, exacerbation of adult-onset Still’s disease, drug eruption and anaphylactic shock.
Conclusion The study suggests that tocilizumab is effective in adult-onset Still’s disease, although the primary endpoint was not met and solid conclusion was not drawn.
- adult-onset Still’s disease
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Handling editor Josef S Smolen
Contributors YK, HK, TA and TT designed the study in collaboration with the Japanese Pharmaceuticals and Medical Devices Agency. YK, KI, TI, KM, HT, YT and TT were involved in patient recruitment, collecting data and managing their clinical research sites. All authors were involved in writing the manuscript and approved the final version. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Funding This study was supported by the Clinical Trial on Development of New Drugs and Medical Devices from the Japanese Ministry of Health, Labour and Welfare under grant number H23-実用化(臨床)-指定-005, and the Japan Agency for Medical Research and Development under grant number JP15lk0103004. Treatment drugs were provided by Chugai Pharmaceutical. The funders had no role in the study design, data collection, data analysis, data interpretation or writing of the report.
Competing interests YK has received grants or speaking fees from AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Janssen, Kissei, Pfizer, Sanofi, Takeda, Mitsubishi-Tanabe and UCB. HK has received grants or speaking fees from AbbVie, Ayumi, Chugai, Mitsubishi-Tanabe, Astellas, Takeda, Eisai, Novartis, Sanofi, Eli Lilly, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer and Janssen. KI has received grants or speaking fees from Tanabe-Mitsubishi Pharma, AbbVie, Bristol-Myers KK, Eisai, UCB, Pfizer Japan, Takeda Pharmaceutical, Eli Lilly, Astellas Pharma, Chugai Pharmaceutical and Kyowa Hakko Kirin. IT has received grants or speaking fees from Chugai, Ono, Pfizer, Mitsubishi-Tanabe and Astellas. KM has received grants or speaking fees from AbbVie, Chugai, Mitsubishi-Tanabe, Astellas, Takeda, Eisai, UCB, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer and Janssen. HT has received grants or speaking fees from Pfizer, Daiichi Sankyo and Mitsubishi-Tanabe. YT has received grants or speaking fees from Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai Pharmaceutical, Astellas Pharma, AbbVie, MSD, Eli Lilly, YL Biologics, Daiichi Sankyo, Sanofi, Janssen, Pfizer, Kyowa Kirin, Eisai and Ono. HT and TA have nothing to declare. TT has received research grants or speaking fees from Astellas Pharma, Bristol-Myers KK, Chugai Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Teijin Pharma, AbbVie GK, Asahi Kasei Pharma, Mitsubishi-Tanabe Pharma, AstraZeneca KK, Eli Lilly Japan KK, Novartis Pharma KK, AbbVie GK, Nippon Kayaku, Janssen Pharmaceutical KK, Taiho Pharmaceutical and Pfizer Japan.
Patient consent Obtained.
Ethics approval The institutional review board at each site approved the study.
Provenance and peer review Not commissioned; externally peer reviewed.
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