This protocol addresses patients under 18 years with systemic juvenile idiopathic arthritis (systemic JIA) who have developed macrophage activation syndrome (MAS) and have not reached the required disease-control targets on their current therapy.
Macrophage activation syndrome is a serious complication of systemic JIA, presenting with fevers, markedly elevated ferritin levels, cytopenias, elevated liver enzyme levels, low fibrinogen levels, and high triglyceride levels. Up to 40% of systemic JIA cases are associated with MAS — a secondary hemophagocytic syndrome that is life-threatening and requires urgent recognition and treatment.
Initial therapy — an IL-1 or IL-6 inhibitor (anakinra, canakinumab, or tocilizumab) combined with systemic glucocorticoids, with or without a calcineurin inhibitor (cyclosporin A or tacrolimus) — did not achieve the required targets: inactive disease, resolution of fevers, normalisation of ferritin, resolution of cytopenias, and normalisation of liver enzyme, fibrinogen, and triglyceride levels. This protocol defines the next step.
The approach centres on an alternative interleukin inhibitor, with switching among or between the IL-1 and IL-6 inhibitor classes as clinically indicated. The complete agent selection, sequencing, and monitoring framework are available in the full protocol.