Research Summary

Dupilumab Improves Health-Related Quality of Life, Respiratory Symptoms in Patients with COPD and Type 2 Inflammation

Edited by:
Anthony Calabro, MA

Key Highlights

  • Dupilumab 300 mg every 2 weeks improved St. George’s Respiratory Questionnaire (SGRQ) total and domain scores vs placebo at 52 weeks.
  • Dupilumab led to greater reductions in Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS:COPD) total scores and all symptom domains, including breathlessness, cough and sputum, and chest symptoms.
  • Higher proportions of dupilumab-treated patients achieved established minimal clinically significant differences in both SGRQ and E-RS:COPD.
  • Treatment-emergent adverse events were similar between the dupilumab and placebo groups.

In a prespecified pooled analysis of the phase 3 BOREAS and NOTUS trials published in CHEST, investigators assessed the effect of add-on dupilumab on patient-reported outcomes in chronic obstructive pulmonary disease (COPD) with type 2 inflammation. Building on prior efficacy data on exacerbation reduction and lung function, this analysis focused on health-related quality of life and respiratory symptom burden over 52 weeks, using St. George’s Respiratory Questionnaire (SGRQ) and the Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS:COPD) instruments.

BOREAS and NOTUS were randomized, double-blind, placebo-controlled phase 3 trials in adults aged 40 to 85 years with physician-diagnosed COPD, post-bronchodilator forced expiratory volume in one second 30% to 70% predicted, type 2 inflammation (blood eosinophils ≥ 300 cells/μL), and a history of at least 2 moderate or 1 severe exacerbation in the prior year. All patients received background triple therapy (inhaled corticosteroid + long-acting muscarinic antagonist + long-acting β₂-agonist) or dual bronchodilator therapy if inhaled corticosteroids were contraindicated.

Patients were randomized 1:1 to dupilumab 300 mg subcutaneously every 2 weeks or placebo for 52 weeks. Outcomes included change from baseline in SGRQ total and domain scores (symptoms, activity, impacts) and E-RS:COPD total and domain scores (breathlessness, cough and sputum, chest symptoms). Minimal clinically significant difference (MCID) thresholds were predefined for total and domain scores, and responder analyses were performed. Safety was evaluated in all treated patients.

Study Findings

In the pooled intention-to-treat population, 1,660 patients (830 per arm) reached week 52. Baseline characteristics were similar between groups; most patients were White (86.9%), male (66.8%), and former smokers (~70%). Baseline SGRQ total scores were approximately 50 in both arms, and baseline E-RS:COPD total scores were approximately 13.

At week 52, dupilumab was associated with greater improvements in the SGRQ total score compared with placebo, with a least-squares mean difference of −3.4 (95% CI, −5.0 to −1.8; P < .0001). Domain analyses showed additional benefits across symptoms (−3.5; 95% CI, −5.5 to −1.5; P = .0006), activity (−4.0; 95% CI, −5.9 to −2.1; P < .0001), and impacts (−2.9; 95% CI, −4.6 to −1.1; P = .0012). Improvements were evident from week 4 and sustained through week 52.

For E-RS:COPD, dupilumab produced a greater reduction in total score vs placebo (least squares mean difference, −0.9; 95% CI, −1.4 to −0.4; P = .0006). Domain differences favored dupilumab for breathlessness (−0.6; 95% CI, −0.9 to −0.3; P < .0001), cough and sputum (−0.2; 95% CI, −0.3 to 0.0; P = .0096), and chest symptoms (−0.1; 95% CI, −0.3 to 0.0; P = .0856).

Responder analyses showed that more dupilumab-treated patients achieved MCID thresholds. For SGRQ total score, 51.4% vs 44.6% met the ≥ 4-point improvement threshold (OR, 1.3; 95% CI, 1.1-1.6; P = .0089), with similar patterns at ≥ 8 and ≥ 12 points. For the E-RS:COPD total score, 38.4% vs 30.6% achieved a ≥ 2-point reduction (OR, 1.4; 95% CI, 1.2-1.8; P = .0007). Across all E-RS:COPD domains, higher responder rates were also observed with dupilumab.

In the pooled safety population, treatment-emergent adverse events occurred in 72.1% of dupilumab-treated patients and 71.0% of placebo-treated patients. The most frequent events (≥ 5% in both groups) included nasopharyngitis, headache, COVID-19, COPD, and upper respiratory tract infection.

Clinical Implications

According to the study authors, these findings indicate that add-on dupilumab provides clinically meaningful improvements in health-related quality of life and respiratory symptoms for patients with COPD and type 2 inflammation already receiving triple therapy. The consistent benefits across SGRQ and E-RS:COPD total and domain scores support the use of validated patient-reported outcomes alongside spirometry and exacerbation data to guide COPD management in this population.

Expert Commentary

“This pooled analysis of the BOREAS and NOTUS trials showed that dupilumab treatment, compared with placebo, had clinically meaningful improvements in health-related quality of life and respiratory symptoms in patients with COPD and type 2 inflammation,” the researchers concluded. “These improvements were seen across total and individual domain scores for SGRQ (symptoms, activity, and impacts) and E-RS:COPD (breathlessness, cough and sputum, and chest symptoms).”

Reference
Bhatt SP, Rabe KF, Hanania NA, et al. Effect of dupilumab on health-related quality of life and respiratory symptoms in patients with COPD and type 2 inflammation: BOREAS and NOTUS. CHEST. 168(1).