In the phase 3 BOREAS trial, dupilumab has demonstrated significant risk reduction in acute exacerbations, improved lung functions and quality of life (QoL) among patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation.¹ According to Professor Surya Bhatt, a principal investigator of the BOREAS trial, dupilumab has shown the potential of halting the vicious cycle of exacerbations and lung function decline in these patients, offering them an alternative for better COPD control.¹

COPD causes a progressive decline in lung function and can be life-threatening.¹ Although chronic airway inflammation is central to the pathogenesis of COPD, the heterogeneity of underlying pathophysiology and comorbidities may complicate its management.² Previous studies have shown that type 2 inflammation is present in up to 40% of COPD patients and is associated with an increased risk of exacerbations.¹ Specifically, cytokines including interleukin-4/13 (IL-4/13) are key drivers of type 2 inflammation, elevating the blood eosinophil (bEOS) levels, and fractional exhaled nitric oxide (F_ENO), which result in the pathological changes of COPD.¹ Triple therapy is the current standard of care (SoC) in patients with frequent COPD exacerbations and high bEOS.¹ Yet, for patients with high exacerbation risks despite the use of triple therapy, novel treatment options to optimize disease management are needed. Promising candidates such as biologics, like dupilumab, that target specific inflammatory pathways have been proven effective in other chronic inflammatory diseases.³

The BOREAS trial was a phase 3, double-blind, randomized, placebo trial that evaluated the safety and efficacy of dupilumab among COPD patients with high exacerbation risks, despite optimized SoC.¹ The patients had bEOS ≥300 cells/mL, ≥1 severe exacerbation(s) or ≥2 moderate exacerbations, despite the use of triple therapy.¹ Dupilumab was investigated as an add-on therapy to the SoC triple therapy.¹ Enrolled patients were randomized 1:1 to receive either 300mg dupilumab subcutaneously (SQ) every 2 weeks (Q2W) (n=471) or a matching placebo (n=468) for 52 weeks.¹

The primary endpoint was the annualized rate of moderate or severe exacerbations of COPD, which was found to be significantly lower with the dupilumab group [0.78 events per year (E/y); 95% CI: 0.64-0.93)] vs. the placebo group (1.10 E/y; 95% CI: 0.93-1.30) with a rate ratio of 0.70 (95% CI: 0.58-0.86; p<0.001).¹ The secondary endpoints included change in the pre-bronchodilator forced expiratory volume in 1 second (FEV₁) at week 12 and 52.¹ Numerical improvements were noted as early as at week 2.¹ By week 12, the dupilumab group reached a least squares mean (LSM) change of 160ml (95% CI: 126-195) vs. LSM change of 77ml (95% CI: 42-112) in the placebo group, amounting to an LSM difference of 83mL (95% CI: 42-125; p<0.001).¹ The difference was sustained until the end of the study through week 52 (LSM difference=83mL; 95% CI: 38-128; p<0.001).¹ Among patients with baseline F_ENO of ≥20 parts per billion (ppb), the annualized rates of moderate-to-severe exacerbation were significantly lower in the dupilumab group vs. the placebo group.¹ Similarly, the change in FEV₁ was also significantly higher in the dupilumab group vs. the placebo group.¹

The St. George’s Respiratory Questionnaire (SGRQ) was used to evaluate QoL, and that numerical improvements were observed as early as at week 4.¹ At week 52, dupilumab demonstrated a statistically significant improvement of -3.4 (95% CI: -5.5 to -1.3; p=0.002) point in LSM change vs. placebo.¹ Furthermore, numerically more patients achieved a ≥4-point improvement in their SGRQ score with dupilumab.¹ Similarly, the Evaluating-Respiratory Symptoms in COPD (E-RS-COPD) score was also used to evaluate respiratory symptoms, and that dupilumab was found to improve significantly by -1.1 (95% CI: -1.8 to -0.4; p=0.001) point in LSM change at week 52 compared with placebo.¹

In summary, the promising results of the BOREAS trial in terms of reduced exacerbation frequency, lung improved function and QoL have suggested the potential role of dupilumab as an add-on therapy for COPD patients with high exacerbation risk, despite the use of SoC triple therapy.¹