TOPLINE:

Emapalumab, an anti-interferon gamma antibody that has effectively managed macrophage activation syndrome (MAS) in patients with Still’s disease, also controlled MAS in patients with systemic lupus erythematosus (SLE) who did not adequately respond to high-dose glucocorticoids.

METHODOLOGY:

• A prospective, open-label, single-arm study enrolled eight pediatric patients (62.5% female; median age, 16 years) with SLE who had MAS and had an inadequate response to high-dose intravenous glucocorticoids.
• MAS diagnosis required having a fever, a serum ferritin level > 684 ng/mL, and two of these labs: platelets ≤ 181 × 10⁹/L, aspartate aminotransferase (AST) levels > 48 U/L, triglycerides > 156 mg/dL, or fibrinogen level ≤ 360 mg/dL.
• Patients had not been treated with etoposide within the past month and were not currently receiving canakinumab, JAK inhibitors, TNF inhibitors, tocilizumab, or anakinra.
• After a loading dose of 6 mg/kg emapalumab, patients received 3 mg/kg every 3 days for days 4-16 and then 3 mg/kg twice a week for days 17-28.
• A complete response was defined by an eight-component composite endpoint comprising the absence of MAS clinical signs and symptoms (visual analog scale [VAS] ≤ 1/10 cm) plus white blood cell and platelet counts above the lower limit of normal; lactate dehydrogenase, AST and alanine aminotransferase < 1.5 times the upper limit of normal; fibrinogen > 100 mg/dL; and ≥ 80% decline in ferritin from baseline (and < 2000 ng/mL). A partial response was defined as VAS < 4 cm and normalization of ≥ 3 MAS-related laboratory parameters.

TAKEAWAY:

• Four patients (50%) had a complete response at week 8 with a median 41 days to first response, and six patients (75%) had an overall response (complete or partial) at 8 weeks with a median 26 days to first overall response.
• Median duration of emapalumab treatment was 16 days, and no recurrent MAS events were reported during 1 year of follow-up.
• The average dose of glucocorticoids was reduced by 93%, from 9.3 mg/kg/d at baseline to 0.65 mg/kg/d at week 8.
• Four patients had serious adverse drug events, and 15 infections were reported in seven patients (87.5%), with one discontinuation due to adverse events but no infusion-related reactions or deaths.

IN PRACTICE:

“These data further support the role of interferon-gamma as a pivotal cytokine in patients with MAS in SLE,” the authors reported. “The efficacy and safety profile of emapalumab in patients with MAS in SLE was similar to patients with MAS in Still’s disease,” with median glucocorticoid dosing reduced by 96.8% from baseline to week 8.

SOURCE:

Alexei A. Grom, MD, a professor of pediatrics at Cincinnati Children’s Hospital and the University of Cincinnati College of Medicine in Cincinnati, presented the findings at the American College of Rheumatology’s Pediatric Rheumatology Symposium (PRSYM) 2026 in Minneapolis.

LIMITATIONS:

This study included only eight participants and had one withdrawal.

DISCLOSURES:

The research was funded by Sobi Inc. Grom has consulted for and/or received grants or contracts from Novartis, AB2 Bio, Novimmune, Kiniksa, Lilly, and Sobi Inc. and reported receiving royalties from UpToDate. One study author was an employee of Sobi.