Efficacy and safety of emapalumab in macrophage activation syndrome

Ann Rheum Dis. 2023 Jun;82(6):857-865. doi: 10.1136/ard-2022-223739. Epub 2023 Mar 31.


Objectives: Macrophage activation syndrome (MAS) is a severe, life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD). The objective of this study was to confirm the adequacy of an emapalumab dosing regimen in relation to interferon-γ (IFNγ) activity by assessing efficacy and safety. The efficacy outcome was MAS remission by week 8, based on clinical and laboratory criteria.

Methods: We studied emapalumab, a human anti-IFNγ antibody, administered with background glucocorticoids, in a prospective single-arm trial involving patients who had MAS secondary to sJIA or AOSD and had previously failed high-dose glucocorticoids, with or without anakinra and/or ciclosporin. The study foresaw 4-week treatment that could be shortened or prolonged based on investigator's assessment of response. Patients entered a long-term (12 months) follow-up study.

Results: Fourteen patients received emapalumab. All patients completed the trial, entered the long-term follow-up and were alive at the end of follow-up. The investigated dosing regimen, based on an initial loading dose followed by maintenance doses, was appropriate, as shown by rapid neutralisation of IFNγ activity, demonstrated by a prompt decrease in serum C-X-C motif chemokine ligand 9 (CXCL9) levels. By week 8, MAS remission was achieved in 13 of the 14 patients at a median time of 25 days. Viral infections and positive viral tests were observed.

Conclusions: Neutralisation of IFNγ with emapalumab was efficacious in inducing remission of MAS secondary to sJIA or AOSD in patients who had failed high-dose glucocorticoids. Screening for viral infections should be performed, particularly for cytomegalovirus.

Trial registration number: NCT02069899 and NCT03311854.

Keywords: Still's disease, adult-onset; arthritis, juvenile; biological therapy; inflammation; therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Arthritis, Juvenile* / complications
  • Arthritis, Juvenile* / diagnosis
  • Arthritis, Juvenile* / drug therapy
  • Follow-Up Studies
  • Glucocorticoids / therapeutic use
  • Humans
  • Macrophage Activation Syndrome* / diagnosis
  • Macrophage Activation Syndrome* / drug therapy
  • Macrophage Activation Syndrome* / etiology
  • Prospective Studies
  • Still's Disease, Adult-Onset* / drug therapy


  • Emapalumab
  • Antibodies, Monoclonal
  • Glucocorticoids

Associated data

  • ClinicalTrials.gov/NCT02069899
  • ClinicalTrials.gov/NCT03311854