Efficacy, safety and effect on gene expression profiling of anakinra in systemic-onset juvenile idiopathic arthritis: final results of a randomised, double-blind, placebo-controlled trial (ANAJIS)

Purpose

To investigate efficacy and safety of anakinra in systemic-onset juvenile idiopathic arthritis patients. To assess treatment effect on gene expression profiling, immune response to anti-pneumococcal Pneumo23 vaccine, serum amyloid A level, serum ferritin level and the percentage of glycosylated ferritin.

Methods

Multicenter randomized double-blind trial. The primary objective was to compare the efficacy of a one-month treatment with anakinra 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 and normalization or a decrease of at least 50% of both CRP and first hour ESR compared to baseline. Intention-to-treat analysis. Secondary objectives included tolerance and efficacy assessment over 12 months and treatment effect on blood gene expression profiling.

Results

At one month, there was a significant difference in the response rate between patients treated with anakinra (8/12) and placebo (1/12). During the double-blind phase, 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. Eight patients discontinued anakinra before Month 12: painful injections during the double-blind phase (2 patients, both on placebo), ileocolic symptoms leading to the diagnosis of Crohn's disease (1 patient), transient hepatic cytolysis (one case), lack of efficacy or a disease flare (4 cases). Gene expression profile analyses showed a set of gene pathways dysregulated in SOJIA whose expression dramatically changed upon anakinra treatment.