Canakinumab for Treatment of Adult-Onset Still's Disease to Achieve Reduction of Arthritic Manifestation (CONSIDER): phase II, randomised, double-blind, placebo-controlled, multicentre, investigator-initiated trial.

Abstract

BACKGROUND:

Inhibition of interleukin (IL)-1 represents a promising treatment option in adult-onset Still's disease (AOSD).

OBJECTIVE:

To investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multicentre, double-blind, randomised, placebo-controlled trial.

METHODS:

Patients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each) were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks) or placebo. The primary endpoint was the proportion of patients with a clinically relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28>1.2).

RESULTS:

At enrolment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab and 5.3 in the placebo group, respectively. In the intention-to-treat analysis, 12 patients (67%) in the canakinumab group and 7 patients (41%) in the placebo group fulfilled the primary outcome criterion (p=0.18). In the per-protocol analysis, significantly higher American College of Rheumatology (ACR) 30% (61% vs 20%, p=0.033), ACR 50% (50% vs 6.7%, p=0.009) and ACR 70% (28% vs 0%, p=0.049) response rates were observed in the canakinumab group compared with the placebo group. Two patients in the canakinumab group experienced a serious adverse event.

CONCLUSION:

Although the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD.

• Authors: Claudia Kedor, Joachim Listing, Jan Zernicke, Anja Weiß, Frank Behrens, Norbert Blank, Joerg Christoph Henes, Joern Kekow, Andrea Rubbert-Roth, Hendrik Schulze-Koops, Eva Seipelt, Christof Specker, Eugen Feist
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 79 Issue 8 Pg. 1090-1097 (08 2020) ISSN: 1468-2060 [Electronic] England
• PMID: 32404342 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• canakinumab

Topics

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