RELATIONSHIP BETWEEN IMPROVEMENT IN LUNG FUNCTION AND SYMPTOMS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE WITH DUPILUMAB
Author(s)
Surya P Bhatt, MD1, Chris E. Brightling, MD, PhD2, Fernando J. Martinez, MD, MS3, Ernesto Mayen Herrera, BSc, MSc4, Mei Zhang, PhD4, Mena Soliman, MSc5, Danen M. Cunoosamy, PhD6, Rosa Faner, PhD7;
1University of Alabama at Birmingham, Birmingham, AL, USA, 2Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, United Kingdom, 3University of Massachusetts Chan, Worcester, MA, USA, 4Sanofi, Morristown, NJ, USA, 5Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA, 6Sanofi, Cambridge, MA, USA, 7University of Barcelona, IDIBAPS, CIBER, Barcelona, Spain
1University of Alabama at Birmingham, Birmingham, AL, USA, 2Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, United Kingdom, 3University of Massachusetts Chan, Worcester, MA, USA, 4Sanofi, Morristown, NJ, USA, 5Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA, 6Sanofi, Cambridge, MA, USA, 7University of Barcelona, IDIBAPS, CIBER, Barcelona, Spain
OBJECTIVES: In chronic obstructive pulmonary disease (COPD), the correlation between lung function improvements and changes in patient-reported outcomes (PROs) has previously been reported as modest. In BOREAS and NOTUS, dupilumab reduced exacerbations, and improved lung function, quality of life and symptoms in patients with COPD and type 2 inflammation. This post hoc analysis aims to examine the correlation between lung function improvement and PROs in patients receiving dupilumab.
METHODS: BOREAS (NCT03930732) and NOTUS (NCT04456673), phase 3, randomized, double-blind, placebo-controlled trials, enrolled patients with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophils ≥300 cells/µL) on inhaled triple therapy. Patients received add-on dupilumab 300 mg or placebo q2w for 52 weeks. Endpoints were: Pearson correlation coefficient (r) between Week 52 change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) and changes in St. George’s Respiratory Questionnaire (SGRQ) (total and activity scores), Evaluating Respiratory Symptoms in COPD (E-RS:COPD) (total and chest symptoms scores), and total effect (95% CI) and mediation percentage (mediator: change in pre-bronchodilator FEV1).
RESULTS: Weak, yet significant correlations were observed between change in pre-bronchodilator FEV1 and SGRQ total (r=−0.26; P<0.001) and activity scores (r=−0.22; P<0.001), as well as E-RS:COPD total (r=−0.21; P<0.001) and chest symptoms scores (r=−0.16; P<0.001). Total effect (95% CI) of dupilumab vs placebo on PROs was −3.58 (−5.39, −1.77; P<0.001) for SGRQ and −1.00 (−1.59, −0.40; P=0.001) for E-RS:COPD total scores. Improvement in pre-bronchodilator FEV1 mediated 24% and 18% of the total effect on SGRQ and E-RS:COPD total scores, respectively.
CONCLUSIONS: The presence of significant causal mediation and significant weak correlations between improvements in lung function and changes in PROs suggests that enhanced lung function may contribute to PRO improvements, alongside other influencing factors.
METHODS: BOREAS (NCT03930732) and NOTUS (NCT04456673), phase 3, randomized, double-blind, placebo-controlled trials, enrolled patients with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophils ≥300 cells/µL) on inhaled triple therapy. Patients received add-on dupilumab 300 mg or placebo q2w for 52 weeks. Endpoints were: Pearson correlation coefficient (r) between Week 52 change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) and changes in St. George’s Respiratory Questionnaire (SGRQ) (total and activity scores), Evaluating Respiratory Symptoms in COPD (E-RS:COPD) (total and chest symptoms scores), and total effect (95% CI) and mediation percentage (mediator: change in pre-bronchodilator FEV1).
RESULTS: Weak, yet significant correlations were observed between change in pre-bronchodilator FEV1 and SGRQ total (r=−0.26; P<0.001) and activity scores (r=−0.22; P<0.001), as well as E-RS:COPD total (r=−0.21; P<0.001) and chest symptoms scores (r=−0.16; P<0.001). Total effect (95% CI) of dupilumab vs placebo on PROs was −3.58 (−5.39, −1.77; P<0.001) for SGRQ and −1.00 (−1.59, −0.40; P=0.001) for E-RS:COPD total scores. Improvement in pre-bronchodilator FEV1 mediated 24% and 18% of the total effect on SGRQ and E-RS:COPD total scores, respectively.
CONCLUSIONS: The presence of significant causal mediation and significant weak correlations between improvements in lung function and changes in PROs suggests that enhanced lung function may contribute to PRO improvements, alongside other influencing factors.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO80
Topic
Clinical Outcomes
Topic Subcategory
Clinician Reported Outcomes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas