Long-Term Efficacy of Canakinumab in Childhood Colchicine Resistant Familial Mediterranean Fever

Objective: To study the role of canakinumab, a selective fully human monoclonal anti-IL-1β antibody, in the treatment of children with colchicine resistant (CR) FMF with a long-term extension.
Methods: In this open-label, single-arm study we enrolled CR-FMF children, with ≥1 FMF attacks per month, including one confirmed by the investigators. In part I patients received the 1st dose of canakinumab (2 mg/kg, max 150 mg) via subcutaneous injection during the subsequent attack and then every 4 weeks for three times. Primary outcome was the proportion of patients with ≥50% reduction in FMF attack rate during the treatment vs. pretreatment period. Patients then entered the long-term extension study (part II).
Results: Seven patients (median age 9.5 yrs) received treatment. In part I, 6/7 (86%) attained the primary outcome. The median attack rate was reduced by 89% from 2.7 to 0.3 per 28 days. Elevated median baseline CRP normalized by Day 8 with ESR and SAA by Day 28. In part II patients (no drop-outs) were followed for a median of 17 (range 13-25) months. During this period, 3 patients experienced 6 attacks (0.05 attacks per patient month). The global physician assessment was rated as very good for all patients. 22 adverse events were recorded in 5 patients, with 11 in each study part. None were serious or led to medication discontinuation.
Conclusion: This study demonstrated the long-term therapeutic effect of canakinumab in children with CR-FMF. Adverse events were manageable.