Canakinumab improves systemic juvenile idiopathic arthritis regardless of fever
Treatment with canakinumab resulted in rapid, sustained improvements in active systemic juvenile idiopathic arthritis, regardless of whether the patient had a fever at initiation, according to data published in Arthritis & Rheumatology.
“Canakinumab, a selective anti-IL-1-beta monoclonal antibody, tested in 3 Phase II-III trials, demonstrated fast onset of action in sJIA, followed by sustained efficacy associated with glucocorticoid discontinuation in a substantial number of patients, with a well-characterized long-term safety profile,” Hermine I. Brunner, MD, MSc, MBA, of the Cincinnati Children’s Hospital Medical Center, and colleagues wrote.
“An early response to canakinumab seemed to be a predictor of long-term control of sJIA features,” they added. “However, little is known about potential differences in response to canakinumab between sJIA patients with and without fever or other systemic features (rash, lymphadenopathy, hepatosplenomegaly) at the time of treatment initiation.”
To assess the long-term efficacy and safety of canakinumab (Ilaris, Novartis) among patients with systemic JIA, and analyze response in those with and without fever at initiation, Brunner and colleagues conducted a prospective, open-label active treatment study. Participants included 123 patients aged 2 years to 19 years with active systemic JIA, 70 with fever and 52 without ever. Open-label treatment included 4 mg/kg of subcutaneous canakinumab every 4 weeks.
Efficacy measures included the adapted JIA American College of Rheumatology (aJIAACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and clinically inactive disease (CID)/clinical remission on medication (CR), evaluated by either JADAS (CIDJADAS/CRJADAS) or ACR criteria (CIDACR/CRACR). Among the total participants, 84 completed the study, with a median duration of 1.8 years.
According to the researchers, efficacy based on aJIAACR 50/70/90/100 was comparable in both groups by day 15 in both subgroups, with 60%, 48.6%, 37.1% and 24.3% demonstrating efficacy, respectively, in the fever group. In the non-fever group, efficacy was seen in 67.3%, 48.1%, 34.6% and 19.2%, respectively. These percentages increased as the study progressed. By month 6, CRJADAS and CRACR were achieved in 24.3% and 37.1% patients respectively, with fever, and in 7.3% and 23.1%, respectively, in those without fever.
In addition, the median time to CRJADAS or CRACR onset was 57 and 30 days, respectively in the fever group, and 58 and 142 days, respectively, in the non-fever group. An aJIAACR50 response by day 15 was the strongest predictor for achieving CRJADAS (OR = 13; 95% CI, 4-42) or glucocorticoid discontinuation (OR = 19; 95% CI, 3–114). Among the 57.7% of patients who received glucocorticoids at baseline, 38% discontinued said glucocorticoids and 29.6% reached a daily dose of less than 0.2 mg/kg, with no difference between the two fever groups.
In all, 10.6% tolerated a sustained canakinumab dose reduction to 2 mg/kg. There were no new safety findings.
“Canakinumab provided rapid and sustained high responses in sJIA patients with either articular or systemic phenotypes, accompanied by a significant ability to taper glucocorticoids,” Brunner and colleagues wrote. “Sustained canakinumab tapering could be obtained in a minority of patients with well-controlled disease activity and at least 6 months after canakinumab initiation. An early response to canakinumab in keeping with results from the previous study was the strongest predictor of CR, giving physicians tangible clinical elements on which to base their decision-making when treating sJIA.”