Is anti-interferon-gamma therapy effective for treating Macrophage Activation Syndrome (MAS)?

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Last updated: June 14, 2025View editorial policy

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From the Guidelines

Anti-interferon-gamma therapy is a recommended treatment for Macrophage Activation Syndrome (MAS), particularly in patients who have failed high-dose glucocorticoids, as it has shown efficacy in targeting the underlying pathogenic pathways involved in MAS. The use of anti-interferon-gamma therapy, such as emapalumab, has been supported by recent studies, including a systematic review informing the EULAR/PReS guidelines for the management of Still's disease 1. This therapy works by neutralizing interferon-gamma, a key cytokine that drives the hyperinflammation and immune dysregulation characteristic of MAS.

Some key points to consider when using anti-interferon-gamma therapy for MAS include:

  • The importance of early initiation of treatment, as delayed treatment can lead to worse outcomes
  • The need for careful monitoring of patients for increased infection risk, particularly tuberculosis, as interferon-gamma plays an important role in antimicrobial defense
  • The potential for anti-interferon-gamma therapy to be used in combination with other treatments, such as high-dose glucocorticoids and IL-1 inhibitors, to achieve optimal outcomes
  • The importance of specialist care, typically by rheumatologists or hematologists experienced in managing hyperinflammatory conditions, to ensure safe and effective use of anti-interferon-gamma therapy.

According to the EULAR/PReS recommendations for the diagnosis and management of Still's disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still's disease, MAS treatment should rely on high-dose glucocorticoids, IL-1 inhibitors, ciclosporin, and interferon-γ inhibitors 1. The recommendations emphasize the key role of expert centers for difficult-to-treat patients and highlight the need for a better understanding of the pathogenic pathways underlying Still's disease, particularly in patients with MAS.

Overall, the use of anti-interferon-gamma therapy for MAS is supported by recent evidence and should be considered as part of a comprehensive treatment approach, taking into account the individual patient's needs and circumstances.

From the Research

Macrophage Activation Syndrome (MAS) and Anti-Interferon-Gamma Therapy

  • Macrophage Activation Syndrome (MAS) is a condition characterized by an overactive immune response, which can lead to tissue damage and organ dysfunction.
  • The use of anti-interferon-gamma therapy in treating MAS is an area of interest, as interferon-gamma plays a crucial role in the immune response.

Effectiveness of Anti-Interferon-Gamma Therapy

  • According to 2, anti-interferon-gamma antibodies have been tested in several autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, with promising results.
  • However, the effectiveness of anti-interferon-gamma therapy in treating MAS specifically is not directly addressed in the provided studies.
  • Studies such as 3 and 4 discuss the complex role of interferon-gamma in autoimmunity and the impact of anti-interferon-gamma autoantibodies on immunodeficiency, but do not provide direct evidence for its use in MAS.

Related Conditions and Treatment Outcomes

  • 5 discusses the characteristics and outcomes of anti-interferon gamma antibody-associated adult onset immunodeficiency, highlighting the challenges in treating this condition.
  • 6 explores the role of anti-interferon autoantibodies in adult-onset immunodeficiency syndrome and severe COVID-19 infection, but does not provide direct evidence for the use of anti-interferon-gamma therapy in MAS.
  • The provided studies suggest that anti-interferon-gamma therapy may have potential in treating certain autoimmune conditions, but its effectiveness in MAS remains unclear due to the lack of direct evidence.

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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