Anifrolumab-A Potential New Systemic Sclerosis Treatment.

Area of Science:

• Immunology
• Rheumatology
• Dermatology
• Vascular Biology
• Fibrosis Research

Background:

• Systemic sclerosis (SSc) is a rare autoimmune disease marked by inflammation, vascular injury, and fibrosis.
• Current therapies exist, but treatments targeting early pathogenic mechanisms are needed.
• Type I interferons (IFN-I) are key mediators linking immune dysregulation to vascular and fibrotic damage in SSc.

Purpose of the Study:

• To review evidence supporting IFN-I blockade with anifrolumab as a novel therapeutic strategy for SSc.
• To evaluate the role of IFN-I signaling in SSc pathogenesis and anifrolumab's therapeutic potential.
• To focus on the IFN signature, interferon-stimulated genes (ISGs), and their association with disease activity and organ involvement.

Main Methods:

• Narrative review of preclinical, translational, and emerging clinical studies.
• Evaluation of the role of IFN-I signaling in SSc.
• Assessment of anifrolumab's therapeutic potential, including its effect on IFN signature and ISG expression.

Main Results:

• Anifrolumab, an antibody targeting the IFN-I receptor subunit 1 (IFNAR1), inhibits all IFN-I isoforms.
• IFNAR blockade suppresses JAK-STAT activation and ISG expression, modulating vascular injury, immune activation, and fibrosis.
• Early findings and ongoing trials suggest potential benefits in SSc patients, especially those with high IFN signature or severe disease.

Conclusions:

• IFN-I pathway inhibition is a promising therapeutic approach for systemic sclerosis.
• Anifrolumab demonstrates potential for treating SSc by targeting key pathogenic mechanisms.
• Ongoing clinical trials are crucial to determine anifrolumab's efficacy, safety, and optimal patient selection in SSc.