Is emapalumab (anti-interferon-gamma monoclonal antibody) approved for treating Macrophage Activation Syndrome (MAS) in pediatric patients?

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Last updated: June 14, 2025View editorial policy

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From the Guidelines

Emapalumab is not approved for treating Macrophage Activation Syndrome (MAS) in pediatric patients, but it may be used off-label due to its efficacy in neutralizing interferon-gamma, a key cytokine involved in the hyperinflammation characteristic of MAS. The medication is only FDA-approved for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) in pediatric and adult patients with refractory, recurrent, or progressive disease or intolerance to conventional HLH therapy 1. While MAS is considered a secondary form of HLH that occurs in patients with underlying rheumatic diseases, emapalumab does not have regulatory approval specifically for MAS.

Some key points to consider when treating MAS include:

  • High-dose corticosteroids are the mainstay of treatment, but they may not be sufficient to control hyperinflammation in all patients 1
  • Interleukin-1 (IL-1) inhibitors, such as anakinra, and interferon-gamma inhibitors, such as emapalumab, may be effective in treating MAS, especially in patients who have failed high-dose corticosteroids 1
  • The optimal therapeutic strategy for MAS relies on early use of IL-1 or IL-6 inhibitors associated with short-duration glucocorticoids (GC) 1
  • Expert centers play a key role in managing difficult-to-treat patients with MAS 1

In terms of emapalumab's efficacy in treating MAS, a case control trial (CCT) described the efficacy and safety of emapalumab in 14 patients with MAS who had failed high-dose GCs, with 13 of the 14 patients (93%) achieving a complete response, and one patient having a partial response 1. However, it is essential to note that emapalumab is not approved for this indication, and its use in treating MAS would be off-label.

From the Research

Emapalumab Approval for Pediatric Patients

  • Emapalumab is approved for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) in pediatric patients, as stated in the study 2.
  • The study 2 mentions that emapalumab is approved for treatment of primary HLH that is refractory, recurrent, progressing or intolerant to current HLH treatments in both adult and pediatric patients.
  • However, the approval status of emapalumab for treating Macrophage Activation Syndrome (MAS) in pediatric patients is not explicitly stated in the provided studies.

Emapalumab Use in Macrophage Activation Syndrome

  • The study 3 investigates the efficacy and safety of emapalumab in patients with MAS secondary to systemic juvenile idiopathic arthritis (sJIA) or adult-onset Still's disease (AOSD).
  • The study 4 develops a population pharmacokinetic/pharmacodynamic model for emapalumab in patients with MAS associated with Still's disease.
  • The study 5 mentions that emapalumab was tested in a clinical trial in 14 sJIA-MAS patients, with 93% of MAS remission, but does not provide information on the approval status.

Pediatric Patient Considerations

  • The study 6 provides information on the clinical spectrum and current management of systemic JIA-associated MAS in a large patient sample, but does not discuss emapalumab approval.
  • The studies do not provide a clear answer to whether emapalumab is approved for treating MAS in pediatric patients, but suggest that it may be used as a treatment option in certain cases, as seen in 3, 4, and 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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