Emapalumab Demonstrates Promising Results in Macrophage Activation Syndrome Treatment
核心洞察
Emapalumab effectively neutralized interferon-gamma (IFNg) in patients with macrophage activation syndrome (搜索) (MAS), leading to disease responses in over 80% of patients.
A significant portion of patients achieved complete response (CR) at Week 8, with even higher rates observed when excluding lactate dehydrogenase (LDH) normalization from CR criteria.
Treatment with emapalumab allowed for substantial reduction in corticosteroid doses, minimizing long-term exposure and associated side effects.
Emapalumab has shown promising efficacy and safety in treating macrophage activation syndrome (搜索) (MAS), a life-threatening complication of rheumatic diseases, particularly systemic juvenile idiopathic arthritis. Data from two open-label, single-arm interventional studies, NI-0501-06 (NCT03311854) and NI-0501-14 (EMERALD; NCT05001737), were presented at the American College of Rheumatology (ACR) Convergence 2024, revealing that emapalumab effectively neutralized IFNg and yielded disease responses in over 80% of patients.
Study Details and Outcomes
The studies, led by Alexei Grom, MD, analyzed data from 39 patients with MAS in Still’s disease (搜索) who had an inadequate response to high-dose glucocorticosteroids. Patients received a 6 mg/kg loading dose of emapalumab, followed by 3 mg/kg every 3 days from days 4–16, then 3 mg/kg twice weekly until Day 28 or longer if insufficient clinical response. The primary efficacy endpoint was complete response (CR) at Week 8, defined by investigator assessment of disease resolution (visual analog scale [VAS] ≤1/10) and normalization of 7 MAS-related laboratory parameters.
The patient cohort was primarily female (79.5%) with a median age of 12 years. Approximately 76.9% had received biologics for acute MAS in Still’s disease (搜索) prior to enrollment. Results showed that 53.8% of participants achieved a CR at week 8 (95% CI, 37.2-69.9), and 85% achieved a CR at any time. A post-hoc sensitivity analysis excluding lactate dehydrogenase (LDH) normalization brought the CR at week 8 to 69.2% (95% CI, 52.4-83.0). The overall response rate at week 8 was 82.4%, with responses observed as early as day 5 and a median time to first OR at 2.3 weeks. Clinical MAS remission was achieved by 82.1% of participants, with a median time to clinical remission of 3.3 weeks, and 94.9% were alive at week 8.
Impact on Corticosteroid Use
An important finding was the ability to reduce prednisolone-equivalent glucocorticoid doses from a mean of 9.7 mg/kg/day at baseline to 0.8 mg/kg/day by week 8. A significant proportion of participants (72%) were able to taper to no more than 1 mg/kg/day by Week 8, and 44% were able to taper to no more than 0.5 mg/kg/day. This reduction is clinically significant, as it minimizes the long-term exposure to corticosteroids and their associated side effects.
Safety and Tolerability
Emapalumab was generally well-tolerated, with 6 serious adverse events (AEs) reported in 4 participants and 14 infusion-related AEs reported in 8 participants. This safety profile supports its use in managing MAS, even in patients who respond to corticosteroids but require prolonged tapering.
Expert Commentary
According to Dr. Grom, emapalumab could benefit patients even those who respond to corticosteroids, because the taper is very, very slow. And he remembers in his clinical practice that where they would taper steroids over a 2-, 3-month period, and still will have recurrence of this condition at the end of the taper. So even if the patients do respond to corticosteroids, the taper takes time, and the overall exposure of those patients to corticosteroids could be actually substantial with all these side effects that come with it.