Emapalumab rapidly controls MAS in patients with Still’s disease

Macrophage activation syndrome (MAS) is a life-threatening complication of Still's disease. In 2 prospective, open-label studies, NI-0501-06 and EMERALD, emapalumab rapidly controlled MAS in >80% of patients –when it occurred– and allowed clinically meaningful reductions in glucocorticoid dosing in 72% of those with an initial inadequate response to high-dose glucocorticoid treatment.

MAS is characterised by IFNγ-driven macrophage activation and systemic hyperinflammation. Emapalumab provides rapid and targeted neutralisation of IFNγ. Dr Alexei Grom (Cincinnati Children's Hospital, OH, USA) presented data from 2 pooled prospective, open-label studies in patients with Still's disease and MAS not sufficiently resolved with high-dose glucocorticoids: the phase 2 NI-0501-06 trial (NCT03311854) and the phase 3 EMERALD trial (NCT05001737) [1–3]. A total of 39 participants, with a mean age of 12 years and 80% women, received emapalumab for 4 weeks or until remission. The primary efficacy endpoint was complete response (CR) after 8 weeks. CR was a composite endpoint with 8 components, all of which had to be met: absence of clinical signs and symptoms of MAS (visual analogue scale <1 cm) and 7 laboratory parameters relevant to MAS.

After 8 weeks, 21 (53.8%) participants achieved CR, and 33 (85%) achieved CR at any time. When lactate dehydrogenase (LDH) was excluded from the endpoint, the CR rate at week 8 increased to 69.2%. By week 8, 32 (82.4%) participants had at least a partial response. Dr Grom added that 32 (82.1%) participants achieved investigator-assessed clinical MAS remission after a median of 3.3 weeks. Two participants had died after 8 weeks.

The high and quick response rate allowed for significant glucocorticoid dose tapering: 72% of participants had clinically meaningful reductions in glucocorticoid dosing to ≤1 mg/kg/day. At baseline, the mean dose was 9.7 mg/kg/day, which decreased to 2.9 mg/kg/day at week 2 and to 0.8 mg/kg/day at week 8. No new safety issues with emapalumab were noted. There were 6 serious adverse drug reactions in 4 participants and 14 infusion-related reactions in 8 participants, none of which were serious. Most of the 22 reported infections were viral and resolved spontaneously or with standard treatment.

1. Grom A, et al. Efficacy and safety of emapalumab in children and adults with macrophage activation syndrome (MAS) in Still's disease: Results from a phase 3 study and a pooled analysis of two prospective trials. Abstract L19, ACR Convergence 2024, 14–19 November, Washington DC, USA.
2. De Benedetti F, et al. Nat Rev Rheumatol. 2021;17(11):678-91.
3. De Benedetti F, et al. Ann Rheum Dis. 2023;82(6):857-65.

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Posted on 13 January 202513 January 2025