A phase 3 international trial of 939 patients with chronic obstructive pulmonary disease found that dupilumab reduced type 2 inflammatory biomarkers compared with placebo.

The findings suggest that biologic therapy could be an option for a subset of patients with chronic obstructive pulmonary disease (COPD) characterized by type 2 inflammation. Blood eosinophil counts and exhaled nitric oxide (FeNO) were identified as predictors of greater treatment response.

All participants had blood eosinophil counts of at least 300 cells/μL at screening and were receiving triple inhaled therapy (inhaled corticosteroid, a long-acting beta-2 agonist, and a long-acting muscarinic antagonist). Patients were randomized to receive 300 mg of dupilumab or placebo every 2 weeks for 52 weeks. This analysis evaluated add-on dupilumab against the current standard of care in patients who continue to exacerbate despite triple therapy.

By week 52, dupilumab-treated patients showed larger median reductions in several biomarkers than the placebo group:

• Total serum immunoglobulin E (IgE): –22.5% vs –0.9%

• Fractional exhaled nitric oxide (FeNO): –28.6% vs –6.9%

• Plasma eotaxin-3: –8.8% vs –0.4%

• Serum pulmonary and activation-regulated chemokine (PARC): –14.4% vs –0.8%

Eosinophil counts remained relatively stable in both groups.

The analysis found that higher blood eosinophils and FeNO were linked to greater reductions in moderate or severe exacerbations. Treatment-by-biomarker interaction effects were statistically significant for baseline eosinophil count, screening eosinophil count , and baseline FeNO, but not for IgE, eotaxin-3, or PARC.

Among current and former smokers, dupilumab reduced FeNO by a least squares mean difference of –5.7 ppb (parts per billion) and–7.9 ppb, respectively. Smoking status did not alter overall treatment effect.

At week 52, 26% of patients receiving dupilumab had a FeNO decrease of 10 ppb or more, compared with 18% on placebo. Among former smokers, the difference was more pronounced (30% vs 18%).

The study authors concluded that elevated eosinophil counts and FeNO may help identify COPD patients most likely to benefit from dupilumab, supporting biomarker-guided strategies similar to those already established in asthma. If validated in further trials, this biomarker-guided approach could bring the first precision biologic therapy to COPD, a field where treatment options remain limited.

The trial was conducted at 275 sites in 24 countries and funded by Sanofi and Regeneron.

Full disclosures can be found in the published study.

Source: The Lancet Respiratory Medicine