Tocilizumab in patients with adult-onset still's disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial.

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.

• Authors: Yuko Kaneko, Hideto Kameda, Kei Ikeda, Tomonoti Ishii, Kosaku Murakami, Hyota Takamatsu, Yoshiya Tanaka, Takayuki Abe, Tsutomu Takeuchi
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 77 Issue 12 Pg. 1720-1729 (12 2018) ISSN: 1468-2060 [Electronic] England
• PMID: 30279267 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Glucocorticoids
• tocilizumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antirheumatic Agents (therapeutic use)
• Double-Blind Method
• Drug Resistance
• Female
• Glucocorticoids
• Humans
• Male
• Middle Aged
• Still's Disease, Adult-Onset (drug therapy)