BRUGES, BELGIUM – Canakinumab, an investigational interleukin-1b antibody also known as ACZ885, has been shown to lessen symptoms of systemic juvenile idiopathic arthritis more than placebo.
The medication, which has yet to be licensed in any country, is administered once a month by subcutaneous injection, instead of intravenous infusion.
The endpoint of the study was a reduction in disease activity by 30% according to American College of Rheumatology Pediatric criteria (ACR Pedi 30), which were modified for the study to include absence of fever, according to Dr. Nicolino Ruperto of the Pediatric Rheumatology International Trials Organization (PRINTO) and Istituto G Gaslini in Genoa, Italy.
Results from a phase III, manufacturer-sponsored, randomized controlled trial (n = 84) of canakinumab showed that a single injection of 4 mg/kg lessened symptoms by 30% or more in 83.7% of patients in the treatment arm (n = 43), compared with 9.8% in the placebo arm (n = 41), at 15 days (Pediatr. Rheum. 2011;9[Suppl 1]:O21).
Patients enrolled in the study were between 2 and 19 years old, with active disease but no macrophage activation syndrome. For the study group as a whole, the mean disease duration was 3.4 years; mean CRP 200.6 mg/L, mean number of active joints was 14.1; and mean prednisone equivalent therapy was 0.3 mg/kg per day.
Dr. Ruperto told the conference that the study participants had spiking intermittent fever at enrollment lasting at least 3 days, and they were allowed to continue on methotrexate or corticosteroids during the trial, but no biological agents besides the study medication.
A majority of patients in the treatment arm (67.4%) achieved ACR Pedi 50 improvement, compared with 4.9% for placebo, and about a third (32.6%) in the study arm saw improvement of ACR Pedi 100, compared with none for placebo. Both ACR Pedi 30 and ACR Pedi 50 responses with canakinumab remained significantly higher than with placebo at day 29.
Adverse events occurred in 55.8% of canakinumab and 39% of placebo patients. Dr. Ruperto said that the most frequently reported adverse events in the study group were upper respiratory problems and gastrointestinal complaints. No patients discontinued the trial because of side effects; however, 6 patients in the treatment arm and 37 in the placebo arm discontinued because for lack of therapeutic effect.
Two deaths occurred in the study group after the completion of the trial, during the long-term follow-up period, Dr. Ruperto told the congress. Both deaths were due to macrophage activation syndrome; one complicated with sepsis and the other with pulmonary hypertension.
The study was funded by Novartis. Dr. Ruperto reported having no financial conflicts of interest. Two of his coinvestigators are Novartis shareholders and one is a Novartis employee.