Anti–IL-33 Biologics in COPD: Francesca Polverino, MD, PhD

Interleukin 33 (IL-33) biology differs from type 2 (T2) inflammation in ways that could allow biologic therapy to reach patients with chronic obstructive pulmonary disease (COPD) regardless of blood eosinophil count, according to Francesca Polverino, MD, PhD, Lester and Sue Smith Professor of Medicine at Baylor College of Medicine.

In an interview with The American Journal of Managed Care^® at the 2026 Global Initiative for Chronic Obstructive Lung Disease (GOLD) International COPD Conference, Polverino discussed how IL-33 differs from T2 inflammation, what a meaningful signal on mucus outcomes might look like, and the changes that could most improve outcomes in COPD over the next 5 years.

How IL-33 Differs From T2 Inflammation

IL-33 is an alarmin, a cytokine produced by the bronchial epithelium, Polverino explained. It sits upstream of the T2 inflammation that has drawn so much attention in COPD because the biologics approved for the disease work preferentially in people with high eosinophil counts, mostly 300 in peripheral blood.

“It is not a T2-only cytokine,” Polverino said. Stress or trauma to the epithelium, such as an exacerbation, a virus, or cigarette smoking, can prompt its secretion. Polverino noted that a recent trial showed benefit from an anti–IL-33 biologic in people with COPD regardless of eosinophil count.

Only a small share of patients, between 20% and 30%, have high blood eosinophil counts, according to Polverino. Treating patients regardless of eosinophil count would reach a large part of the COPD population that does not meet the criteria today.

What Mucus Outcomes May Show

Mucus plugging seen on CT scans is associated with mortality and hospitalization from COPD, Polverino said. However, not every patient with CT evidence of plugging has symptoms, and the reverse is also true. Some people with chronic bronchitis, phlegm, and a productive cough show no clear plugging on CT.

IL-33 works preferentially by increasing mucus production and changing mucus composition, Polverino said, so drugs targeting it should act mainly on mucus, cough, and symptoms of the chronic bronchitis phenotype. Patients with that phenotype were first treated with roflumilast and then with azithromycin every other day. Polverino said the IL-33–targeting drugs now offer another option.