IL-6 and its role in thyroid eye disease

In an interview with Ophthalmology Times, Alon Kahana, MD, PhD, discussed interleukin-6 (IL-6), a signaling molecule crucial in regulating the immune system and its role in autoimmune diseases, particularly thyroid eye disease (TED). IL-6 influences T cells, B cells, and inflammatory cells, driving immune processes that can be beneficial in infections but harmful in autoimmune conditions. TED often affects patients with autoimmune thyroid disorders, such as Graves’ disease or Hashimoto’s thyroiditis, and involves orbital inflammation.

Currently, TED is primarily treated with teprotumumab (Tepezza), targeting the IGF-1 receptor pathway, which reduces orbital congestion and proptosis. However, this therapy does not address the root autoimmune triggers, leading to frequent symptom relapses post-treatment. IL-6 inhibitors, such as tocilizumab (FDA-approved for rheumatologic conditions), target the IL-6 receptor. However, receptor blockade can trigger a feedback loop that increases receptor expression, limiting efficacy.

A promising alternative under clinical trial is pacibekitumab, an IL-6 ligand-blocking antibody. It binds to the ligand before receptor interaction, avoiding feedback loops and potentially offering greater efficacy. This mechanism suppresses IL-6-mediated immune activity, including T-cell regulation, cytokine release, and orbital fibroblast activation, which drives TED inflammation. Preliminary trials indicate good safety and tolerability for this approach.

Challenges in translating preclinical findings into clinical success include optimizing drug formulation, delivery, dosage, and ensuring efficacy without toxic off-target effects. TED is an orphan disease, complicating patient recruitment for trials. Trials must also assess long-term safety, efficacy, and diverse patient responses to meet FDA standards.

Looking ahead, personalized medicine could revolutionize TED treatment by identifying biomarkers that predict disease severity and therapeutic response. This approach, already transformative in cancer care, could tailor IL-6 inhibition and other treatments to individual immune triggers, offering more effective, targeted interventions while preventing blindness and disfigurement in TED patients.

Kahana is the owner of Kahana Oculoplastic & Orbital Surgery in Livonia and Ann Arbor, Michigan, and is a professor of oculoplastic surgery and vice chair for academic affairs in the Department of Ophthalmology at Oakland University William Beaumont School of Medicine in Royal Oak, Michigan.

For more information on Dr. Kahana and his work, visit https://url.us.m.mimecastprotect.com/s/cc2XCDkA2ASXDZBOTWfQIj_LZB?domain=drkahana.com/