General Information

Ilaris (canakinumab) is a human monoclonal anti-human IL-1ß antibody. Canakinumab binds to human IL1ß and neutralizes its activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1a or IL-1 receptor antagonist (IL-1ra).

Ilaris is specifically indicated for the treatment of active Systemic Juvenile Idiopathic Arthritis (SJIA) in patients aged 2 years and older.

Ilaris is specifically indicated the treatment of active Still’s disease, including Adult-Onset Still’s Disease.

Ilaris is supplied as a lyophilized powder for solution for subcutaneous injection. The recommended dose for SJIA patients with a body weight greater than or equal to 7.5kg is 4mg/kg (with a maximum of 300mg) administered every four weeks.

Clinical Results

The FDA approval of Ilaris for SJIA was based on two studies, (SJIA Study 1 and SJIA Study 2). Subjects enrolled were aged 2 to less than 20 years with a confirmed diagnosis of SJIA at least 2 months before enrollment. The subjects were allowed to continue their stable dose of methotrexate, corticosteroids, and/or NSAIDs without change, except for tapering of the corticosteroid dose as per study design in SJIA Study 2.
SJIA Study 1
This randomized, double-blind, placebo-controlled, single-dose 4-week study assessed the short term efficacy of Ilaris in 84 subjects who were randomized to receive a single subcutaneous dose of 4 mg/kg Ilaris or placebo. The primary endpoint was the superiority of Ilaris versus placebo in the proportion of patients who achieved at least 30% improvement in an adapted pediatric American College of Rheumatology (ACR) response criterion which included both the pediatric ACR core set (ACR30 response) and absence of fever (temperature less than or equal to 38°C in the preceding 7 days) at Day 15. At Day 15 the ACR30 was 84% versus 10% in the Ilaris versus placebo arms, respectively. At Day 29 the ACR30 rates were 81% versus 10%, respectively. Among the patients who returned for a Day 15 visit, the mean change in patient pain score (0-100 mm visual analogue scale) was -50.0 mm on Ilaris, as compared to +4.5 mm on placebo. The mean change in pain score among Ilaris treated patients was consistent through Day 29. All patients treated with laris had no fever at Day 3 compared to 87% of patients treated with placebo.
SJIA Study 2
This randomized, double-blind, placebo controlled, withdrawal study evluated flare prevention by Ilaris. Flare was defined by worsening of greater than or equal to 30% in at least 3 of the 6 core Pediatric ACR response variables combined with improvement of greater than or equal to 30% in no more than 1 of the 6 variables, or reappearance of fever not due to infection for at least 2 consecutive days. The study consisted of two major parts. 177 patients were enrolled in the study and received 4mg/kg Ilaris subcutaneously every 4 weeks in Part I and 100 of these patients continued into Part II to receive either Ilaris 4mg/kg or placebo subcutaneously every 4 weeks. Of the total 128 patients who entered the open-label portion taking corticosteroids, 92 attempted corticosteroid tapering. Fifty-seven (62%) of the 92 patients who attempted to taper were able to successfully taper their corticosteroid dose and 42 (46%) discontinued corticosteroids. Part II was a randomized withdrawal design to demonstrate that the time to flare was longer with Ilaris than with placebo. Follow-up stopped when 37 events had been observed resulting in patients being followed for different lengths of time. The probability of experiencing a flare over time in Part II was statistically lower for the Ilaris treatment group than for the placebo group. This corresponded to a 64% relative reduction in the risk of flare for patients in the Ilaris group as compared to those in the placebo group.

The FDA approval of Ilaris in adults with AOSD is based on the pharmacokinetic exposure and extrapolation of the established efficacy of Ilaris in SJIA patients. Efficacy of Ilaris was also assessed in a randomized, double-blind, placebo-controlled study that enrolled 36 patients (22 to 70 years old) diagnosed with AOSD. The efficacy data were generally consistent with the results of a pooled efficacy analysis of SJIA patients.