Higher-dose canakinumab therapy for refractory macrophage activation syndrome in children with systemic juvenile idiopathic arthritis: two case reports

Macrophage activation syndrome (MAS) is a life-threatening, potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA) appears in non-remitted fever, cytopenia, coagulopathy, liver and CNS dysfunctions. Triggers of MAS could be disease activity, infections and medications. Known IL-1 is the key cytokine in pathogenesis of MAS and SJIA, and disease flare associated with increased amounts of different cytokines, especially IL-1β. Many cases of MAS are medically-refractory to traditional doses of cytokine inhibition and may require increased dosing of biologic cytokine blockade. Interleukin-1 (IL-1) is typically a key cytokine in the pathogenesis of sJIA and associated MAS. When MAS occurs in the setting of sJIA treated with IL-1 inhibitors, then increased dosing of IL-1 blockers may be beneficial. This has been shown for anakinra, an IL-1 receptor antagonist, but this drug is currently not available worldwide. Another IL-1 blocker, canakinumbab (CKB), is a monoclonal antibody that blocks IL-1β, but does not also block IL-1α like anakinra. Herein, we describe 2 sJIA patients who developed MAS on standard doses of CKB (4 mg/kg). Both patients received an increased dose of CKB: 150 mg (7.5 and 12.5 mg/kg, respectively) with rapid and complete resolution of MAS. Later the CKB doses was tapered to normal regimen. No side effects or adverse events were noticed during usage of increased CKB doses. Increased dosing of CKB should be considered for CKB-treated sJIA patients who develop MAS on standard dosing.