Tocilizumab in patients with adult-onset still's disease refractory to glucocorticoid treatment

A randomised, double-blind, placebo-controlled phase III trial

Yuko Kaneko, Hideto Kameda, Kei Ikeda, Tomonoti Ishii, Kosaku Murakami, Hyota Takamatsu, Yoshiya Tanaka, Takayuki Abe, Tsutomu Takeuchi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAnnals of the Rheumatic Diseases
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Adult-Onset Still's Disease
Refractory materials
Glucocorticoids
Placebos
Therapeutics
Drug Eruptions
Interleukin-6 Receptors
tocilizumab
Rheumatology
Anaphylaxis
Least-Squares Analysis
Double-Blind Method
Hip
Labels
Necrosis
Safety

Keywords

  • adult-onset Still's disease
  • efficacy
  • randomised
  • tocilizumab

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Tocilizumab in patients with adult-onset still's disease refractory to glucocorticoid treatment : A randomised, double-blind, placebo-controlled phase III trial. / Kaneko, Yuko; Kameda, Hideto; Ikeda, Kei; Ishii, Tomonoti; Murakami, Kosaku; Takamatsu, Hyota; Tanaka, Yoshiya; Abe, Takayuki; Takeuchi, Tsutomu.

In: Annals of the Rheumatic Diseases, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Kameda, Hideto

AU - Ikeda, Kei

AU - Ishii, Tomonoti

AU - Murakami, Kosaku

AU - Takamatsu, Hyota

AU - Tanaka, Yoshiya

AU - Abe, Takayuki

AU - Takeuchi, Tsutomu

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N2 - 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.

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