"We are encouraged by the results of the study, that show canakinumab has the potential to be an effective and fast-acting treatment option with a promising safety profile.”—Nicolino Ruperto, MD, MPH
“We are encouraged by the results of the study, that show canakinumab has the potential to be an effective and fast-acting treatment option with a promising safety profile,” said lead study author Nicolino Ruperto, MD, MPH, a senior scientist of PRINTO, Istituto Di Ricovero a Carattere Scientifico at the Children’s Hospital of Genova, Italy. “Further large scale randomised clinical trials are now on-going to progress its clinical development.”59% respond to canakinumab, half of whom achieve ACR-Pedi 50
In the new open-label staggered dose-escalation study, 23 children with active disease received 1 subcutaneous injection of canakinumab in the dose range 0.5-9 mg/kg. Patients were observed and re-dosed if they relapsed. A relapse was defined as reappearance of fever and/or systemic manifestations of the disease with elevated c-reactive protein (CRP) levels.
Of the 59% of patients who responded to treatment, 100% achieved the American College of Rheumatology Pediatric (ACR Pedi) 50 score within 15 days of receiving canakinumab. Fully 70% of responders were able to taper off of steroids.
Canakinumab permits steroid sparing in JIA
On average, the steroid dose was decreased by 0.054 mg/kg per month in the first 5 months. Four patients reached ‘inactive’ disease status after the first dose. Response was best predicted by the number of active joints. Responders had an average of 9 active joints, compared with 33.5 among non-responders, the study showed.
Of the 23 children enrolled, 12 were male and 11 were female. Participants ranged in age from 4 to 19. They had about 18.5 joints with active arthritis and 23.5 joints with limitation of motion at baseline.
The observed time to relapse upon cessation of canakinumab therapy ranged from 1 to 12 weeks. The median time to relapse was 56 days for doses of <3 mg/kg, 60 days for doses of 3 mg/kg and 90 days for doses of >3 mg/kg, with a 19% (95% CI: 6-41), 17% (6-34) and 7% (1-23) probability of relapse within 1 month, respectively.
The treatment was well tolerated. Adverse events were predominantly mild to moderate in severity. They included infections and gastrointestinal disorders. There were two serious treatment-related adverse events: a worsening nausea in a patient with a history of gastritis and Epstein Barr viral infection in another patient. Both were resolved.
Translating research into practice: Canakinumab versus Anakinra
Kathleen A. Haines, MD, the section chief of pediatric immunology at Hackensack University Medical Center in New Jersey told MSKreport.com that she was impressed that some of the patients in the study achieved a complete remission after 1 dose.
When asked how the new drug may compare to another IL-1 blocker Anakinra (Kineret®, Amgen), she said “Anakinra has an extremely short half-life and needs to be injected daily. This drug looks much more promising, and it may even have a better success rate after several doses.”
“This drug could be extremely useful for JIA patients,” she said. “There is no way to predict its effect on polyarticular disease.”
Dr. Haines said she was disappointed that canakinumab was not effective in patients with more joint involvement. “However,” she said, “that too may be a dosing effect. Perhaps with a weekly or every other dosing schedule they might have done better.“
References
1. Ruperto N, Quartier O, Wulffraat N, et al. A phase II trial with canakinumab (ACZ885), A new IL-1-Beta blocking monoclonal antibody to evaluate the safety and preliminary efficacy in children with systemic juvenile idiopathic arthritis. Presented at: EULAR 2009, June 10-13, 2009; Copenhagen, Denmark. Abstract OP-0298.
PubMed: Related Articles