Safety and efficacy of canakinumab in Japanese patients with phenotypes of cryopyrin-associated periodic syndrome as established in the first open-label, phase-3 pivotal study (24-week results).

Abstract

OBJECTIVES:

Cryopyrin-associated periodic syndrome (CAPS), a rare hereditary auto-inflammatory disease, is associated with mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1 β) release. CAPS generally occurs in early childhood with most patients presenting with periodic fever, skin rash, osteoarthropathy, aseptic meningitis, sensorineural hearing loss and optic neuritis. Canakinumab, a fully human anti-IL-1β monoclonal antibody which binds selectively to IL-1β, has demonstrated good efficacy with CAPS. This is the first study to evaluate the safety and efficacy of canakinumab in Japanese patients with CAPS.

METHODS:

In this open-label study, 19 Japanese CAPS patients aged ≥2 years received canakinumab either 150 mg s.c. or 2 mg/kg for patients with a body weight ≤ 40 kg every 8 weeks for 24 weeks. The primary objective was to assess the proportion of patients who were free of relapse at week 24.

RESULTS:

A complete response was achieved in 18 (94.7%) patients with some requiring a dose and/or a frequency adjustment to attain full clinical response. The majority of patients (14/18; 77.8%) were in remission, i.e. free of relapse at week 24. Auto-inflammatory disease activity as assessed by physician's global assessment declined from baseline to end of the study (score of absent in 10.5% at baseline versus 31.6% at end of the study). Two patients had serious adverse events (SAEs), which resolved with standard treatment. One patient reported a mild injection-site reaction. No malignancies or deaths were reported during the study.

CONCLUSIONS:

Canakinumab 150 mg s.c. every 8 weeks was well-tolerated, highly efficacious and offered a convenient dosing regimen for treating Japanese patients with CAPS.

• Authors: Tomoyuki Imagawa, Ryuta Nishikomori, Hidetoshi Takada, Saoko Takeshita, Neha Patel, Dennis Kim, Karine Lheritier, Toshio Heike, Toshiro Hara, Shumpei Yokota
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2013 Mar-Apr Vol. 31 Issue 2 Pg. 302-9 ISSN: 0392-856X [Print] Italy
• PMID: 23380020 (Publication Type: Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Biomarkers
• Immunosuppressive Agents
• Inflammation Mediators
• canakinumab

Topics

• Adolescent
• Adult
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Biomarkers (blood)
• Child
• Child, Preschool
• Cryopyrin-Associated Periodic Syndromes (blood, diagnosis, drug therapy, immunology)
• Drug Administration Schedule
• Female
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects, therapeutic use)
• Inflammation Mediators (blood)
• Injections, Subcutaneous
• Japan
• Male
• Middle Aged
• Recurrence
• Remission Induction
• Time Factors
• Treatment Outcome
• Young Adult