Efficacy and safety of emapalumab in macrophage activation syndrome

Objectives Macrophage activation syndrome (MAS) is a severe, life threatening complication of systemic juvenile idiopathic arthritis (sJIA) and adult onset Still s disease (AOSD). The objective of this study was to confirm the adequacy of an emapalumab dosing regimen in relation to interferon-gamma (IFNgamma) activity by assessing efficacy and safety. The efficacy outcome was MAS remission by week 8, based on clinical and laboratory criteria. Methods We studied emapalumab, a human anti-IFN-gamma antibody, administered with background glucocorticoids, in a prospective open-label, single-group trial involving patients who had MAS secondary to sJIA or AOSD and had previously failed high-dose glucocorticoids. The study foresaw 4-week treatment that could be shortened or prolonged based on investigators assessment of response. Patients could enter a long-term (12 months) follow-up study. Results Fourteen patients received emapalumab. All patients completed the trial, entered the long-term follow-up and were alive at the end of the follow-up. The investigated dosing regimen, based on an initial loading dose followed by maintenance doses, was appropriate, as shown by rapid neutralisation of IFN-gamma activity, demonstrated by prompt decrease in serum C-X-C motif chemokine ligand 9 (CXCL9) levels. By week 8, remission of MAS was achieved in 13 of the 14 patients at a median time of 25 days. Viral infections and positive viral tests were observed during the trial and during the long-term follow-up. Conclusions Neutralisation of IFN-gamma with emapalumab was efficacious in inducing remission of MAS secondary to sJIA or AOSD in patients who had failed high-dose glucocorticoids.