How IL-33 Targeting Could Expand Biologic Options for COPD Patients

How IL-33 Targeting Could Expand Biologic Options for COPD Patients

November 7, 2026 Dr. Michael Lee – Health Editor Health

Blocking Eosinophil Limits in Chronic Obstructive Pulmonary Disease

Most patients with chronic obstructive pulmonary disease remain excluded from biologic therapies under current eosinophil-based criteria. Biologics currently approved for the condition work preferentially in people with high blood eosinophil counts, mostly 300 in peripheral blood. According to Francesca Polverino, speaking at the GOLD 2026 COPD International Conference in Philadelphia, these type 2-high patients represent roughly 20 percent of the COPD population.

    Key Clinical Takeaways:

  • Eosinophil-based criteria currently limit biologic treatment options to roughly 20 percent of the COPD patient population.
  • The alarmin IL-33 is enriched in the blood and lungs of most patients with COPD, extending far beyond type 2 inflammation.
  • Recent trial data show that targeting the IL-33 pathway can successfully treat patients regardless of their blood eosinophil count.

Blocking IL-33 Reaches Patients Lacking Eosinophil Thresholds

While approved biologics work preferentially in people with high eosinophil counts, IL-33 operates as an alarmin produced directly by the bronchial epithelium. Stress or trauma to the airway lining, such as an exacerbation, a viral infection, or cigarette smoke, prompts its secretion. IL-33 sits upstream of the type 2 inflammation that has drawn significant attention in recent management strategies. Because of this broader expression, a drug targeting the IL-33 pathway can reach the majority of patients who do not meet current eosinophil thresholds.

Anti–IL-33 Biologics in COPD: Francesca Polverino, MD, PhD
Photo: The American Journal of Managed Care

A recently reported successful trial of an IL-33-targeted therapy enrolled patients regardless of their blood eosinophil count. Polverino characterized this ability to treat across the eosinophil spectrum as the central clinical advance offered by the IL-33 pathway.

Drugs Targeting IL-33 Act on Mucus and Chronic Bronchitis

Mucus plugging seen on computed tomography scans is associated with mortality and hospitalization from COPD, but clinical presentation varies widely. Some patients with chronic bronchitis, phlegm, and a productive cough show no clear plugging on imaging scans, while others show plugging without prominent symptoms. IL-33 works preferentially by increasing mucus production and altering mucus composition. Drugs targeting this pathway act mainly on mucus, cough, and symptoms specific to the chronic bronchitis phenotype.

Targeting IL-33 in COPD: Who Benefits and What Remains Unknown

Patients exhibiting this mucus-heavy phenotype historically received roflumilast followed by azithromycin every other day. IL-33-directed therapies now offer an alternative therapeutic avenue for these individuals. In vitro and ex vivo studies using primary bronchial epithelial cells demonstrate that IL-33 exists in reduced and oxidized forms with distinct, complementary roles. The oxidized form contributes predominantly to mucus plugging, whereas the reduced form drives inflammation and inflammatory cell recruitment.

Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider regarding any medical condition, diagnosis, or treatment plan.

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