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SAN DIEGO, CA—Patients with systemic juvenile idiopathic arthritis had rapid, marked, and continued improvement—including a significant increase in functional ability and reduction in pain—when treated with canakinumab compared with placebo, patient-reported outcomes results from two phase 3 trials presented at the 2013 ACR/ARHP Annual Meeting have shown.
Previously, the trials demonstrated the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1β monoclonal antibody, in patients with systemic juvenile idiopathic arthritis. This condition “is associated with severe functional impairment and chronic pain that markedly affects health-related quality of life (HRQoL),” noted Rayfel Schneider, MD, of the Pediatric Rheumatology Collaborative Study Group (PRCSG), Cincinnati, OH.
In the first trial, patients were randomized to canakinumab (n=43) or placebo (n=41) and followed for 1 month. In the second trial, 177 patients (including 71 from the first trial) received open-label canakinumab in Part 1. Part 2 comprised of 100 responders to canakinumab, who were randomized to continue the study drug or to placebo.
The patient-reported outcomes included functional ability by the Childhood Health Assessment Questionnaire (CHAQ), pain as measured on a visual analog scale (VAS) of 0—100mm, and HRQoL by the Child Health Questionnaire–Parent Form (CHQ-PF50) for patients 5—18 years of age, with rating on physical and psychosocial health status.
At the end of the first trial, significant improvement in functional ability was observed with canakinumab (P=0.0002), resulting in an estimated difference (ED) in CHAQ score of -0.69 between the canakinumab and placebo group at Day 29 from baseline. “This ED constitutes about 3.6 times the minimal clinically important difference (-0.19) in the CHAQ score,” Dr. Schneider noted.
Pain intensity significantly declined in the canakinumab vs. placebo groups (both P<0.0001), both at Day 15 (ED, -46.42) and Day 29 (ED, -41.86). Similarly, HRQoL significantly improved from baseline for canakinumab vs. placebo, with an ED in CHQ-PF50 physical health scores of 12.07 and CHQ-PF50 psychosocial health scores of 7.28 (both P<0.005) over 1 month with canakinumab.
“Even more pronounced improvements in functional ability, pain, and HRQoL were observed in Trial 2,” he added. Between baseline and the end of Part 2 of the study, the CHAQ disability score decreased from 1.7 to 0.5 in the canakinumab group, compared with a final score of 0.6 for the placebo group, which received canakinumab during part 1 of the study. Pain intensity decreased from 66.7 to 13.6 (vs. 17.0 for placebo). The CHQ-PF50 physical health status scores increased from 15.8 to 43.6 (vs. 39 for placebo) and the CHQ-PF50 psychosocial health status score from 41.6 to 53.6 (vs. 52.7 for placebo).
The most common adverse event (AE) for all treatment groups was infections. During Trial 1, the most common AEs included nasopharyngitis (7.0%), upper respiratory tract infection (URTI) (7.0%), and diarrhea (7.0%). During Part 1 of Trial 2, common AEs for canakinumab were nasopharyngitis (15.3%), headache (13.0%), cough (11.3%), URTI (10.2%), pyrexia (10.2%), and vomiting (10.2%). During Part 2, they were arthralgia (24.0%), cough (16.0%), nasopharyngitis (14.0%), and pyrexia for canakinumab and nasopharyngitis (14.0%), URTI, and pyrexia and arthralgia (10% each) for placebo.
Long-term extension studies are ongoing to obtain additional safety information.
