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Emapalumab May Improve Response Rates in MAS Treatment
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Key Takeaways
- Emapalumab achieved over 80% disease response in MAS patients, showing promise as a therapeutic option for those unresponsive to glucocorticosteroids.
- The treatment allowed significant glucocorticosteroid dose reduction, with most patients tapering to minimal doses by week 8.
Findings from the first and only controlled study for macrophage activation syndrome were presented at the ACR Convergence.
Alexei Grom, MD
Credit: Cincinnati Children’s
Emapalumab neutralized IFNg in all patients with macrophage activation syndrome (MAS) and yielded disease responses in over 80%, according to new data from 2 open-label, single-arm interventional studies.1
Findings from the NI-0501-06 (NCT03311854) and NI-0501-14 (EMERALD; NCT05001737) studies were presented by Alexei Grom, MD, Research Director, Division of Rheumatology, and Professor, Department of Pediatrics, Cincinnati Children’s, at the American College of Rheumatology (ACR) Convergence 2024, held November 14-19 in Washington, DC.
“MAS is a life-threatening complication of many rheumatic diseases, but it's by far most common in the systemic form of juvenile idiopathic arthritis… it's a life threatening complication, and it certainly remains the one of the major sources of mortality in our field, in general. And there is a clear need for new therapeutic targets, as well as new medications to help these kids,” Grom told HCPLive® during the meeting.
Grom and colleagues analyzed data from 39 patients with MAS in Still’s disease and an inadequate response to high-dose glucocorticisteroids in the first and only controlled study for MAS. Patients received a 6 mg/kg loading dose, 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.2 The primary efficacy endpoint was complete response (CR) at Week 8, defined as investigator assessment of disease resolution (visual analog scale [VAS] ≤1/10) and normalization of 7 MAS-related laboratory parameters.
The participants were mostly female (n = 31; 79.5%), had a median age of 12 years (range, 0.9–64), and 30 (76.9%) had received biologics for acute MAS in Still’s disease prior to study enrollment. Around half of participants (n = 21; 53.8%) achieved a CR at week 8 (95% CI, 37.2-69.9) and 33 (85%) achieved a CR at any time. Participants often missed lactate dehydrogenase (LDH) when not meeting CR criteria. Excluding LDH in a post-hoc sensitivity analysis 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% (n = 32), and overall responses were observed as early as day 5, with a median time to first OR at 2.3 weeks. Most participants (n = 32; 82.1%) achieved investigator-assessed clinical MAS remission at any time (median time to clinical remission, 3.3 weeks) and 37 (94.9%) were alive at week 8.1
Clinical improvement accordingly followed the degree if IFNg neutralization, which was assessed using serum chemokine C-X-C ligand 9. Other biomarkers of hyperinflammation also rapidly reduced after initiating treatment with emapalumab.
Importantly, prednisolone-equivalent GC doses were able to be reduced from a mean of 9.7 mg/kg/day (standard deviation [SD], 9.5) at baseline to 0.8 mg/kg/day (SD, 0.6) by week 8. Most participants (72%, n =28) were able to taper to no more than 1 mg/kg/day by Week 8 and 44% (n = 17) were able to taper to no more than 0.5 mg/kg/day. Emapalumab was generally well-tolerated, with 6 serious adverse events (AEs) reported in 4 participants and 14 infusion-related AEs reported in 8 participants.1
“[Emapalumab could benefit] even those who respond to corticosteroids. We start tapering corticosteroids relatively early, but the taper is very, very slow. And I remember in my clinical practice that where we 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,” Grom said.
REFERENCES
Grom A, Ullman U, Mahmood 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. Presented at: ACR Convergence 2024; November 14-19; Washington, DC. Abstract L19.
De Benedetti F, Grom AA, Brogan PA, et al. Efficacy and safety of emapalumab in macrophage activation syndrome. Ann Rheum Dis. 2023;82(6):857-865. doi:10.1136/ard-2022-223739
