ANAKINRA IN SYSTEMIC-ONSET JUVENILE IDIOPATHIC ARTHRITIS: RESULTS OF A MULTICENTER DOUBLE-BLIND TRIAL (ANAJIS)

Background: Patients with Systemic-Onset Juvenile Idiopathic Arthritis (SOJIA) and a severe, persistently active course are often poorly responsive to existing treatments including methotrexate and etanercept. In some patients treated with interleukin-1 receptor antagonist Anakinra, dramatic clinical improvement has been reported together with modifications of gene expression profiling.Objectives: To evaluate safety and efficacy of anakinra in SOJIA patients with insufficient response to corticosteroids. To assess Anakinra pharmacokinetic and treatment effect on gene expression profiling.Methods: Multicenter randomized double-blind trial. The primary objective was to compare the efficacy of a one-month treatment with anakinra (2 mg/kg subcutaneoulsy daily, maximum 100 mg) to a placebo between 2 groups of 12 patients each. Response was defined by 30% improvement of pediatric ACR core-set criteria for JIA, resolution of fever and systemic symptoms for at least 8 days and a decrease of at least 50% of both CRP and first hour ESR compared to baseline. Intention-to-treat analysis. Secondary objectives included pharmacokinetic analyses, tolerance and efficacy assessement over 12 months. Treatment effect on blood gene expression profiling, anti-pneumococcal response, serum amyloid A level, serum ferritin level and the percentage of glycosylated ferritin were assessed using blood samples collected at Day 1, Month 1 and Month 6.Results: At one month, there was a significant difference in the response rate (primary objective) between patients treated with Anakinra (8/12 responders) and placebo (1/12). The number of adverse events, mainly pain to injections, was similar between both groups. Ten patients from the placebo group switched to Anakinra at Month 1 and 9 were responders at month 2. Between month 2 and month 12, 5 patients stopped treatment. One patient disclosed ileocolic symptoms during the third month leading to the diagnosis of Crohn disease. There were 4 other serious adverse events (3 infections, one vertebral collapse) which outcome was favourable. In 5 other cases, treatment was withdrawn for transient hepatic cytolysis (one case), lack of efficacy (2 cases) or a disease flare (2 cases). Pharmacokinetic analyses showed the highest concentration of Anakinra after 12 and 16 hours in very good responders. The SOJIA signature observed at day 1 rapidly wore off upon initiation of anakinra treatment, allowing us to distinguish patients treated with anakinra from patients treated with placebo. Gene expression profile analyses at month 1 and 6 also showed clear differences between responders and non responders. Finally, this analysis allowed us to identify a set of genes induced by anakinra treatment.Citation: Ann Rheum Dis, volume 67, supplement II, year 2008, page 68Session: Abstract Session: PRES: Biologics and biomarkers in JIA