Ilaris (canakinumab) can reduce disease activity or lead to clinical remission of active systemic juvenile idiopathic arthritis (sJIA) for up to five years with no changes in its safety profile, a long-term extension study shows.
A positive, long-term response to Ilaris allows patients to reduce or discontinue their use of glucocorticoids, although those who respond early to treatment are more likely to sustain their response long-term.
The study “Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials” was published in the journal Annals of the Rheumatic Diseases.
Injected subcutaneously, Ilaris is made of a human antibody that selectively blocks IL-1 beta, an inflammatory mediator key for the development of sJIA. Marketed by Novartis, it is approved for the treatment of periodic syndrome fevers and active sJIA in patients 2 years of age and older.
The medicine’s approval was based on the positive results of Phase 1, Phase 2 and Phase 3 clinical trials, where the therapy demonstrated its safety and efficacy in children and young people with active sJIA. The results of the two Phase 3 clinical trials — β-SPECIFIC 1 (NCT00886769) and β-SPECIFIC 2 (NCT00889863) — showed that Ilaris was able to reduce disease activity and risk of flares, allowing patients to taper off their glucocorticoid therapy.
To evaluate the long-term efficacy and safety of Ilaris, an international team of researchers conducted a Phase 3, open-label, extension study called β-SPECIFIC 3 (NCT00891046). The study included 144 children, from 2 to 19 years old with sJIA and active disease, who participated in the two prior Phase 3 studies and moved to the extension study to continue treatment with Ilaris.
Participants were followed for up to five years, between July 2009 and December 2014, to measure clinical improvements.
Efficacy assessments were performed at least every three months using several validated measures, including the adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR’s clinical remission on medication criteria (CRACR).
After two years of treatment, aJIA-ACR 50/70/90 response rates, or clinical improvements, of 50% were reported in 62% of the patients, rates of 70% in 61%, and of 90% in 54% of patients according to ACR criteria.
Clinical remission — defined as at least six months of clinically inactive disease — was achieved by 18.6% of patients after six months. This proportion increased to 31.6% after two years.
A total of 44.6% of patients achieved low disease activity or clinically inactive disease over the first six months of Ilaris use, which increased to 48.6% at two years and was sustained until the study’s end, up to five years later.
At the end of the study, 15.6% of the patients had stopped glucocorticoid therapy and 22% had tapered their glucocorticoid medications to 0.150 mg/kg/day.
Of the 144 participants initially enrolled, only 75 (42%) completed the long-term study and 102 (58%) stopped taking Ilaris, mainly due to the lack or loss of efficacy, or intolerance. Seven patients discontinued treatment because they achieved clinical remission.
Those considered late responders to treatment discontinued Ilaris more often (25 out of 31, or 81%) compared with early responders (11 out of 38, or 29%).
Early responders were defined as patients who had successfully completed glucocorticoid tapering in the first part of the β-SPECIFIC 2 trial, before entering the long-term extension study; late responders were defined as patients who failed to reduce glucocorticoids use in that study.
According to the results, the long-term safety profile was identical to that the short-term use of Ilaris reported in prior trials. There were 13 cases of macrophage activation syndrome (a life-threatening condition caused by excessive activation and proliferation of certain white blood cells; three cases have previously been reported). No additional deaths or new safety findings were observed.
“Canakinumab’s [Ilaris] effect on systemic features and joints proved to be maintained in the long term particularly in the early responders patients,” the researchers wrote.
As an early response was linked to better long-term outcomes, “time to response will facilitate physicians in their decision making to keep or switch canakinumab [Ilaris] to another treatment in a timely manner,” they added.