AMETHYST: A Retrospective Cohort Study of Treatment Patterns and Outcomes in Patients With Glucocorticoid-Refractory...

Information is limited on the natural history and current treatment patterns in macrophage activation syndrome (MAS), a life-threatening hyperinflammatory syndrome complicating Still's disease (systemic juvenile idiopathic arthritis [sJIA] and adult-onset Still's disease [AOSD]). AMETHYST aimed to describe real-world treatment patterns and outcomes in glucocorticoid (GC)-refractory MAS complicating Still's disease.

In this retrospective cohort study, medical data from January 1, 2012, to March 31, 2023, were abstracted from charts of all eligible patients across eight sites in Europe, Canada, and the United States for index MAS episodes (occurring between January 1, 2012, and September 30, 2022, and meeting eligibility criteria).

Overall, 55 of 64 included patients (86%) had sJIA and 9 of 64 (14%) had AOSD. Most patients (53/64 [82.8%]) were children at index (median age: 7.0 years). MAS was characterized by rash (60.4%), fever (52.8%), and hepatic involvement (49.1%). All patients received GCs; most were also treated with anakinra (48/64 [75%]) and/or ciclosporin (33/64 [51.6%]). Normalization of seven (complete MAS laboratory remission) or at least three (partial remission) prespecified laboratory parameters occurred in 7 of 64 (10.9%) and 41 of 64 patients (64.1%), respectively. GCs were tapered in 50 of 64 patients (78.1%) (median: 39.9 days). Per investigator assessment of clinical signs/symptoms for the index MAS episode, 24 of 64 (37.5%) and 26 of 64 patients (40.6%) had a complete and partial response, respectively. MAS recurred in 20 of 64 patients (31.3%). Seven of 64 patients (10.9%) died, and the estimated one-year survival probability was 93.75%.

Low MAS laboratory remission rates and toxicities of high-dose GCs combined with other treatments highlight the need for safer, more effective therapies.