Patient-Reported Symptom Improvements in Chronic Obstructive Pulmonary Disease Following Dupilumab Treatment: The Mediating Role of Lung Function
Author(s)
Surya P Bhatt, MD1, Rosa Faner, PhD2, Chris E. Brightling, MBBS, PhD3, Ernesto Mayen Herrera, PhD4, Mei Zhang, PhD4, Mena Soliman, PhD5, Danen M. Cunoosamy, PhD6.
1University of Alabama at Birmingham, Birmingham, AL, USA, 2University of Barcelona, IDIBAPS, CIBER, Barcelona, Spain, 3Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, United Kingdom, 4Sanofi, Morristown, NJ, USA, 5Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA, 6Sanofi, Cambridge, MA, USA.
1University of Alabama at Birmingham, Birmingham, AL, USA, 2University of Barcelona, IDIBAPS, CIBER, Barcelona, Spain, 3Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, United Kingdom, 4Sanofi, Morristown, NJ, USA, 5Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA, 6Sanofi, Cambridge, MA, USA.
OBJECTIVES: In chronic obstructive pulmonary disease (COPD), modest correlations have been observed between lung function improvements and changes in patient-reported outcomes (PROs). In BOREAS and NOTUS, dupilumab reduced exacerbations and improved lung function and quality of life in patients with COPD and type 2 inflammation. Safety of dupilumab was consistent with the known dupilumab safety profile. This analysis examines the correlation between lung function improvements and PROs in patients receiving dupilumab for the treatment of COPD.
METHODS: BOREAS (NCT03930732) and NOTUS (NCT04456673), phase 3, randomized, placebo-controlled trials, enrolled patients with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophils ≥300 cells/µL) on triple therapy. Patients received add-on dupilumab 300 mg or placebo q2w for 52 weeks. Endpoints evaluated in dupilumab-treated patients were Pearson correlation coefficient (r) between change from baseline to Week 52 in pre-bronchodilator forced expiratory volume in 1 second (FEV1) and changes in St. George’s Respiratory Questionnaire (SGRQ; total and symptoms scores), Evaluating Respiratory Symptoms in COPD (E-RS:COPD; total and breathlessness scores). Causal mediation analysis was used to estimate the total effect (95% CI) of dupilumab vs placebo on PROs total score (mediator: pre-bronchodilator FEV1) as well as the percentage of mediation.
RESULTS: Weak correlations were observed between change in pre-bronchodilator FEV1 and SGRQ total (r=−0.26; P<0.001) and symptoms scores (r=−0.24; P<0.001), as well as E-RS:COPD total (r=−0.21; P<0.001) and breathlessness scores (r=−0.21; P<0.001). Total effect (95% CI) was −3.58 points (−5.39, −1.77; P<0.001) for SGRQ total scores and −1.00 points (−1.59, −0.40; P=0.001) for E-RS:COPD total scores. Mediation analysis indicated that 24% of the total effects on SGRQ and 18% on E-RS:COPD were attributable to improvements in pre-bronchodilator FEV1.
CONCLUSIONS: Causal mediation and correlation analysis suggest that lung function plays a partial role in the improvement of PROs.
METHODS: BOREAS (NCT03930732) and NOTUS (NCT04456673), phase 3, randomized, placebo-controlled trials, enrolled patients with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophils ≥300 cells/µL) on triple therapy. Patients received add-on dupilumab 300 mg or placebo q2w for 52 weeks. Endpoints evaluated in dupilumab-treated patients were Pearson correlation coefficient (r) between change from baseline to Week 52 in pre-bronchodilator forced expiratory volume in 1 second (FEV1) and changes in St. George’s Respiratory Questionnaire (SGRQ; total and symptoms scores), Evaluating Respiratory Symptoms in COPD (E-RS:COPD; total and breathlessness scores). Causal mediation analysis was used to estimate the total effect (95% CI) of dupilumab vs placebo on PROs total score (mediator: pre-bronchodilator FEV1) as well as the percentage of mediation.
RESULTS: Weak correlations were observed between change in pre-bronchodilator FEV1 and SGRQ total (r=−0.26; P<0.001) and symptoms scores (r=−0.24; P<0.001), as well as E-RS:COPD total (r=−0.21; P<0.001) and breathlessness scores (r=−0.21; P<0.001). Total effect (95% CI) was −3.58 points (−5.39, −1.77; P<0.001) for SGRQ total scores and −1.00 points (−1.59, −0.40; P=0.001) for E-RS:COPD total scores. Mediation analysis indicated that 24% of the total effects on SGRQ and 18% on E-RS:COPD were attributable to improvements in pre-bronchodilator FEV1.
CONCLUSIONS: Causal mediation and correlation analysis suggest that lung function plays a partial role in the improvement of PROs.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO177
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
Biologics & Biosimilars, Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory)