Patients with elevated eosinophils and FeNO levels see greater benefit from dupilumab, researchers say.
Biomarkers of type 2 inflammation may predict therapeutic response to dupilumab in patients with chronic obstructive pulmonary disease, new research shows.
Results of the phase III BOREAS trial offers compelling evidence that has the potential to guide a biomarker-driven approach to treatment, the researchers say.
Their findings were published this month in The Lancet Respiratory Medicine.
“Patients with COPD and type 2 inflammation who were given dupilumab showed reduced type 2 inflammatory biomarkers, with elevated blood eosinophil count and FeNO predicting greater treatment response,” the authors wrote.
“These findings support biomarker-driven treatment strategies to optimise therapy.”
The BOREAS trial was conducted across 275 global sites and involving 939 patients with COPD and blood eosinophil counts ≥300 cells/μL.
Of these, 468 patients were randomly assigned to receive 300mg of dupilumab every two weeks for 52 weeks and 471 were randomly assigned to receive matching placebo.
Three hundred and nineteen participants (34%) were female and 620 (66%) were male. 657 (70%) were former smokers and 282 (30%) were current smokers.
Previous studies with IL-5 pathway inhibitors showed reductions in eosinophil counts but lacked consistent effects on clinical outcomes such as exacerbation rates.
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With increasing recognition of heterogeneity in COPD pathogenesis, the researchers said their analysis added to the growing evidence base supporting a biomarker-guided treatment paradigm, particularly for patients with an eosinophilic or type 2 inflammatory phenotype.
Patients treated with dupilumab – a monoclonal antibody targeting IL-4Rα – exhibited greater reductions in several biomarkers of type 2 inflammation over the 52-week trial period compared with placebo. Key findings included:
- Total IgE: Median reduction of −22.5% with dupilumab vs −0.9% with placebo
- FeNO: −28.6% vs −6.9%
- Eotaxin-3: −8.8% vs −0.4%
- PARC: −14.4% vs −0.8%
“Improvements observed were generally consistent across subgroups, regardless of baseline demographic or disease characteristics,” the authors wrote.
“Safety was consistent with the known dupilumab safety profile. Given the overall results of the BOREAS trial, we hypothesise that type 2 inflammatory biomarkers can have predictive value for the potential response to dupilumab treatment.”
Interestingly, blood eosinophil levels remained stable during treatment, suggesting that clinical benefit was not due to depletion of eosinophils, but rather modulation of broader inflammatory pathways.
Further stratified analysis revealed that patients with higher baseline blood eosinophil counts and FeNO levels experienced a more pronounced reduction in exacerbation risk—highlighting these biomarkers as potential tools for predicting treatment response (p=0.0056 and p=0.043, respectively).
“The results reported in this study demonstrate the efficacy of dupilumab in reducing type 2 inflammatory biomarkers, suggesting a role for type 2 inflammation in COPD, including but not limited to, blood eosinophil count,” the researchers concluded.
“Our results also show that elevated baseline blood eosinophil counts and FeNO concentrations were predictive of treatment response to dupilumab.
“Further studies are needed to explore the mode of action of dupilumab and the role of these type 2 inflammatory biomarkers in the underlying pathobiology of COPD, as well as in the predictive utility of FeNO in patients with COPD and type 2 inflammation.”
