Copenhagen, Denmark, Saturday 13 June 2009: Canakinumab (ACZ885), a new interleukin-1 (IL-1)-beta blocking monoclonal antibody, shows encouraging efficacy and is well tolerated in children with systemic juvenile idiopathic arthritis (sJIA)*, according to a new phase II study presented today at PReS 2009, a joint congress with the 2009 Congress of the European League Against Rheumatism (EULAR) in Copenhagen, Denmark. Of those patients who responded to treatment (59% of initial enrollers), 100% achieved the American College of Rheumatology Paediatric (ACR Pedi) 50** score within only 15 days of receiving canakinumab. Additionally, steroid tapering was seen in the majority of responders and, in 4 cases (18%), 'inactive' disease status was reached. The best baseline parameter for predicting response was the number of active joints (median: 33.5 for non responders, 9 for responders).
Dr Nicolino Ruperto, Senior Scientist of PRINTO***, Istituto Di Ricovero a Carattere Scientifico (IRCCS) Children's Hospital of Genova, Italy, who led the study, said: "JIA is the most common chronic inflammatory disease of childhood, affecting approximately 1 in 1,000 children, and sJIA is the most severe subtype. We are encouraged by the results of the study, that show canakinumab has the potential to be an effective and fast-acting treatment option with a promising safety profile. Further large scale randomised clinical trials are now on-going to progress its clinical development."
This open-label staggered dose-escalation study assessed 23 children with active disease receiving a single subcutaneous (sc) injection of canakinumab in the dose range 0.5-9 mg/kg, followed by an observation period and re-dosing upon relapse. Response was measured according to ACR paediatric criteria. Relapse was defined as reappearance of fever and/orsystemic manifestations of the disease with elevated CRP (c-reactive protein) according to the ACR paediatric criteria for flare.
Of the 23 children enrolled, 12 were males and 11 females, aged 4-19 years. The median baseline physicians' and parents'/patients' global assessment of disease activity were 68.5 and 67mm VAS (Visual Analogue Scale, used to assess disease impact) respectively; CHAQ (Childhood Health Assessment Questionnaire) disability index 2.1; number of joints with active arthritis 18.5; number of joints with limitation of motion 23.5; CRP 136 mg/L; median prednisone equivalent dose 0.33 mg/kg.
The observed time to relapse upon cessation of canakinumab therapy was variable, ranging from 1-12 weeks. The time to relapse was analysed using a frailty model with dose grouping - this included statistically significant baseline covariates such as CRP, WBC (white blood cell) count and steroid dose. The median time to relapse was 56 (95% CI: 32-100), 60 (38-95) and 90 (45-181) days for doses <3, 3, >3 mg/kg, with a 19% (95% CI: 6-41), 17% (6-34) and 7% (1-23) probability of relapse within one month, respectively.
Concurrent steroid use was tapered in 70% of responders. On average, the steroid dose was decreased by an average of 0.054 mg/kg per month in the first 5 months (95% CI: 0.013-0.121). Adverse events experienced by study participants were predominantly mild to moderate in severity, including infections and gastrointestinal disorders. Two serious adverse events (worsening nausea in a patient with a medical history of gastritis and EBV viral infection in another patient) relating to canakinumab, according to the investigator, were resolved during treatment.