Add-on dupilumab cuts exacerbations in patients with COPD, type 2 inflammation

Add-on dupilumab significantly reduced moderate or severe exacerbations in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation compared with placebo, according to the BOREAS trial.

By week 52, patients who received dupilumab had a significantly lower annualized rate of moderate or severe COPD exacerbations than those who were on placebo (0.78 vs 1.10; rate ratio [RR], 0.70; p<0.001). [N Engl J Med 2023;389:205-214]

In addition, lung function, as assessed by prebronchodilator FEV₁*_, was significantly improved with dupilumab vs placebo at week 12 in both  (0.160 vs 0.077 L; least square [LS] mean difference, 0.083 L; p<0.001). “Notably, this improvement was observed within 2 weeks after the initiation of dupilumab and was sustained through week 52,” according to the researchers.

Among patients with a baseline FENO level of ≥20 parts per billion [ppb], the dupilumab group showed a greater reduction in COPD exacerbations (0.70 vs 1.12 events per year; RR, 0.62; p=0.005) and improvement in lung function (0.247 vs 0.120 L; LS mean difference, 0.127 L; p=0.003) than the placebo group. “These findings were consistent with the known role of interleukin (IL)-4 and IL-13 in type 2 inflammation,” the researchers noted.

“The clinical improvements associated with dupilumab — a fully human monoclonal antibody that blocks the shared receptor component for IL-4 and IL-13 — that were observed in this trial confirm the role of IL-4 or IL-13 (or both) in the pathophysiological characteristics of this COPD subpopulation with type 2 inflammation that extends beyond the role of IL-5 and eosinophils,” said the researchers.

This phase III, double-blind, multicentre trial included 939 patients (mean age 65.1 years, 66 percent male) with COPD who had evidence of type 2 inflammation, with baseline mean blood eosinophil count of 401 µl, despite the receipt of standard inhaled triple therapy (inhaled glucocorticoid plus LAMA**-LABA***) for ≥3 months prior to randomization. Participants were randomly assigned to receive subcutaneous dupilumab 300 mg (n=468) or placebo (n=471) once every 2 weeks for 52 weeks in addition to standard triple therapy.

St. George’s Respiratory Questionnaire (SGRQ) and Evaluating Respiratory Symptoms in COPD (E-RS-COPD) scores were used to evaluate patient-reported outcomes from baseline to week 52.

At week 52, an improved SGRQ total score, indicating a better quality of life (QoL), was observed in the dupilumab group than the placebo group (LS mean change from baseline, -9.7 vs -6.4; p=0.002).

More dupilumab-treated patients also achieved a ≥4-point improvement in SGRQ total score at week 52 than the placebo-treated patients (51.5 percent vs 43.1 percent; odds ratio, 1.4; p=0.009).

Patients in the dupilumab group also had significantly less severe respiratory symptoms, as shown by a greater improvement in the E-RS-COPD total score at week 52 (LS mean change from baseline, -2.7 vs -1.6; p=0.001), than those in the placebo group.

In terms of safety profile, adverse events (AEs) of any grade occurred at a similar rate between the dupilumab and placebo groups (77.4 percent vs 76.0 percent), with fewer serious AEs (13.6 percent vs 15.5 percent) observed in the dupilumab group.

Nasopharyngitis (9.4 percent vs 9.6 percent), upper respiratory tract infection (7.9 percent vs 9.8 percent), and headache (8.1 percent vs 6.8 percent) were the most common AEs reported in the dupilumab group vs the placebo group.

“Overall, in symptomatic patients with COPD and evidence of type 2 inflammation who had a high risk of COPD exacerbation despite the use of standard triple therapy, treatment with dupilumab resulted in a lower annualized rate of moderate or severe exacerbations, better lung function and QoL, and less severe respiratory symptoms than placebo,” said the researchers.

“These differences were observed within 2–4 weeks after the initiation of dupilumab and were sustained throughout the 52-week trial period,” they noted.