Canakinumab delivers sustained response in systemic juvenile idiopathic arthritis
Treatment with canakinumab yields a rapid, substantial improvement in disease activity in children with systemic juvenile idiopathic arthritis (sJIA), according to long-term extension data from two phase III pivotal trials. Furthermore, response is sustained for up to 5 years, allowing dose reduction or even discontinuation of glucocorticoids without raising new safety concerns.
“For the first time, early response has been shown to be linked to canakinumab’s long-term survival rendering it as an easy identifiable clinical predictor of long-term maintenance of remission/low disease activity,” they added.
The present analysis included 144 children aged 2–19 years who entered the long-term extension phase, representing 81 percent of the total core population (n=177) in the two trials. Of these, 96 children had shown early response while 48 had late response. Efficacy evaluations including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CRACR) were conducted every 3 months.
Overall, 75 patients (42 percent) completed the extension phase. At 2 years, 49 percent showed a JADAS low disease activity score. The respective aJIA-ACR 50/70/90 response rates were 62 percent, 61 percent and 54 percent. CRACR occurred in 20 percent of patients at month 6 and 32 percent at year 2. These improvements were maintained up to 5 years. [Ann Rheum Dis 2018;doi:10.1136/annrheumdis-2018-213150]
Notably, of the 128 patients taking glucocorticoids at the start of the extension phase, 20 (15.6 percent) discontinued and 28 (22 percent) tapered to 0.150 mg/kg/day by 5 years of canakinumab therapy.
“Exploratory analysis suggested that early response to [the active drug] leads to a better long-term favourable outcome. As such, patients who entered the long-term extension study from the double-blind, placebo-controlled part because they responded to canakinumab quickly and successfully tapered glucocorticoids, fared better than late responders,” the investigators noted.
“The long-term use of the drug was well tolerated and consistent with the safety profile that has been reported in other canakinumab trials,” they continued.
No new safety findings were observed, and the most common adverse events were infections. There were 13 macrophage activation syndrome events documented while on canakinumab (three previously reported), although there were no additional deaths (three previously reported).
“As long as achievement, as much as maintenance, of remission or alternatively low disease activity constitutes the ultimate therapeutic target in order to prevent future organ damages and disease-related comorbidities, time to response will facilitate physicians in their decision making to keep or switch canakinumab to another treatment in a timely manner,” they said.
The study might be limited by the overall low retention rate, with 58 percent of the patients discontinuing canakinumab over 5 years. Additionally, the population included patients with a wide range of canakinumab treatment durations due to the adaptive design chosen to limit placebo and corticosteroid exposures.