BOREAS highlights dupilumab potential in COPD

In the phase III BOREAS trial, the monoclonal antibody dupilumab conferred multiple benefits for individuals with chronic obstructive pulmonary disease (COPD) and type 2 (T2) inflammation.

“[We sought] to evaluate the efficacy and safety of dupilumab in patients with moderate-to-severe COPD with T2 inflammation as indicated by elevated eosinophils (ie, baseline blood eosinophil count ≥300 cells/µL),” said the researchers, led by Dr Surya Bhatt from the University of Alabama at Birmingham in Alabama, US.

“[In our study,] dupilumab significantly improved exacerbations, lung function, quality of life, and symptoms in [this patient setting], both in the overall population and in the Asian subgroup,” said Bhatt and colleagues.

A total of 939 participants (mean age 65.1 years, 66 percent male) were randomized 1:1 to either subcutaneous dupilumab or placebo once every 2 weeks for 52 weeks. Eligible participants had moderate-to-severe disease with a history of high exacerbation risk, had T2 inflammation (mean blood eosinophil count 401 cells/µL), and were on background triple inhaler therapy (inhaled corticosteroids [ICS] plus long-active muscarinic antagonist plus long-acting beta-agonist; 98 percent) if ICS is contraindicated. [APSR 2023, abstract APO7-302]

Dupilumab improved the annualized rate of moderate-to-severe COPD exacerbations relative to placebo (0.78 vs 1.10; 30-percent difference; p<0.001). Dupilumab was also consistently favoured over placebo in the subgroup analysis, with rate ratios ranging between 0.44 and 0.85.

Dupilumab treatment led to improvements in measures of lung function, including prebronchodilator forced expiratory volume in 1 second (FEV₁). The changes from baseline in prebronchodilator FEV₁ were similar at weeks 12 and 52 (least squares mean [LSM] difference 83 mL; p<0.001 for both timepoints). In the Asian subgroup, the LSM difference at week 12 was 43 mL.

The researchers also noted improvements in post-bronchodilator FEV₁, prebronchodilator forced vital capacity, and prebronchodilator forced expiratory flow (FEF_25–75%) with dupilumab relative to placebo.

Moreover, patients treated with dupilumab had better patient-reported outcomes as reflected by the drops in total scores on the St George’s Respiratory Questionnaire (SGRQ; LSM change -3.4; p=0.002) and Evaluating Respiratory Symptoms in COPD (E-RS:COPD; LSM change -1.1; p=0.002) by week 52.

According to the researchers, a lower SGRQ score corresponds to better quality of life, while a lower score on E-RS:COPD indicates a reduction in the severity of respiratory symptoms.

Safety results aligned with the documented safety profile of dupilumab. More than 10 percent of the overall cohort reported any treatment-emergent serious adverse events (SAEs). Overall mortality rate due to any treatment-emergent AE (TEAE) was <2 percent, and about 3 percent had any TEAE that led to permanent discontinuation of the study drug.

The most common TEAES tied to dupilumab use were nasopharyngitis (9 percent), headache (8 percent), and upper respiratory tract infection (8 percent).

The current findings underpin the potential of dupilumab for the treatment of COPD with T2 inflammation, which is associated with more frequent COPD exacerbations. [Allergy 2021;76:1861-1864; J Allergy Clin Immunol 2017;140:1181-1184; AM J Respir Crit Care Med 2020;202:660-671] Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13, which are key and central drivers of T2 inflammation. [Expert Rev Clini Immunol 2017;11:425-437; Allergy 2020;75:1188-1204]

In a press release, dupilumab has been noted as the first and only investigational biologic for COPD that has shown a significant reduction in moderate or severe acute exacerbations relative to placebo, with significant improvement in lung function at 12 and 52 weeks and numerical improvements as early as 2 weeks. [www.sanofi.com/en/media-room/press-releases/2023/2023-05-21-18-17-12-2672904, accessed November 23, 2023]