Michael E. Wechsler MD , Ian D. Pavord MD , Alberto Papi MD , Kenneth R. Chapman MD , Arman Altincatal MS , Nami Pandit-Abid PharmD , Juby A. Jacob-Nara MD , Paul J. Rowe MD , Yamo Deniz MD , Elizabeth Laws PhD , Bolanle Akinlade MD , Nikhil Amin MD , Heribert W. Staudinger MD , David J. Lederer MD , Megan Hardin MD
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Treatment effects were greater in patients with elevated baseline type 2 biomarkers (blood eosinophil count ≥ 150 cells/μL or fractional exhaled nitric oxide ≥ 25 parts per billion).</div></div><div><h3>Research Question</h3><div>What is dupilumab’s long-term efficacy (up to 3 years) in patients with moderate-to-severe type 2 asthma?</div></div><div><h3>Study Design and Methods</h3><div>Patients enrolled in QUEST (receiving placebo or dupilumab), who completed 96 weeks of dupilumab treatment in the open-label extension Long-Term Safety Evaluation of Dupilumab in Patients With Asthma (TRAVERSE) study (NCT02134028), were included. This prespecified analysis evaluated long-term efficacy in patient populations identified by baseline type 2 biomarker level. End points were annualized exacerbation rate (AER) and change from baseline in pre-BD FEV<sub>1</sub> (L), asthma control (5-item Asthma Control Questionnaire), and asthma-related quality of life (Asthma Quality of Life Questionnaire).</div></div><div><h3>Results</h3><div>A total of 663 patients were included. AER was 1.72 to 2.24 at QUEST baseline in dupilumab groups across type 2 populations. AER decreased in populations with elevated type 2 biomarkers to 0.36 to 0.49 during QUEST’s 52-week treatment period, which was sustained over 96 weeks in TRAVERSE. In patients with low type 2 biomarker levels, there was no clinically meaningful AER reduction in QUEST or TRAVERSE, but rates remained below parent study baseline. Similar trends were seen with improvements in pre-BD FEV<sub>1</sub>, 5-item Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire; greatest improvements were seen in groups with one or more elevated type 2 biomarker.</div></div><div><h3>Intrepretation</h3><div>This study suggests that long-term dupilumab treatment results in sustained and clinically meaningful efficacy in patients with moderate-to-severe type 2 asthma characterized by elevated blood eosinophil count and/or fractional exhaled nitric oxide.</div></div><div><h3>Clinical Trial Registration</h3><div>ClinicalTrials.gov; No.: NCT02134028; URL: <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span></div></div>","PeriodicalId":94286,"journal":{"name":"CHEST pulmonary","volume":"3 1","pages":"Article 100072"},"PeriodicalIF":0.0000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Long-Term Efficacy of Dupilumab in Moderate-to-Severe Asthma Phenotyped by Blood Eosinophils and Exhaled Nitric Oxide\",\"authors\":\"Michael E. 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Treatment effects were greater in patients with elevated baseline type 2 biomarkers (blood eosinophil count ≥ 150 cells/μL or fractional exhaled nitric oxide ≥ 25 parts per billion).</div></div><div><h3>Research Question</h3><div>What is dupilumab’s long-term efficacy (up to 3 years) in patients with moderate-to-severe type 2 asthma?</div></div><div><h3>Study Design and Methods</h3><div>Patients enrolled in QUEST (receiving placebo or dupilumab), who completed 96 weeks of dupilumab treatment in the open-label extension Long-Term Safety Evaluation of Dupilumab in Patients With Asthma (TRAVERSE) study (NCT02134028), were included. This prespecified analysis evaluated long-term efficacy in patient populations identified by baseline type 2 biomarker level. End points were annualized exacerbation rate (AER) and change from baseline in pre-BD FEV<sub>1</sub> (L), asthma control (5-item Asthma Control Questionnaire), and asthma-related quality of life (Asthma Quality of Life Questionnaire).</div></div><div><h3>Results</h3><div>A total of 663 patients were included. AER was 1.72 to 2.24 at QUEST baseline in dupilumab groups across type 2 populations. AER decreased in populations with elevated type 2 biomarkers to 0.36 to 0.49 during QUEST’s 52-week treatment period, which was sustained over 96 weeks in TRAVERSE. In patients with low type 2 biomarker levels, there was no clinically meaningful AER reduction in QUEST or TRAVERSE, but rates remained below parent study baseline. 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Long-Term Efficacy of Dupilumab in Moderate-to-Severe Asthma Phenotyped by Blood Eosinophils and Exhaled Nitric Oxide
Background
Asthma treatment aims to reduce symptom severity and exacerbation risk. Dupilumab, a human monoclonal antibody, blocks the shared receptor for IL-4/IL-13, key drivers of type 2 inflammation. In the Evaluation of Dupilumab in Patients With Persistent Asthma (QUEST) study (NCT02414854), add-on dupilumab every 2 weeks vs placebo was shown to significantly reduce severe asthma exacerbations and improve prebronchodilator (BD) FEV1 in patients with uncontrolled, moderate-to-severe asthma. Treatment effects were greater in patients with elevated baseline type 2 biomarkers (blood eosinophil count ≥ 150 cells/μL or fractional exhaled nitric oxide ≥ 25 parts per billion).
Research Question
What is dupilumab’s long-term efficacy (up to 3 years) in patients with moderate-to-severe type 2 asthma?
Study Design and Methods
Patients enrolled in QUEST (receiving placebo or dupilumab), who completed 96 weeks of dupilumab treatment in the open-label extension Long-Term Safety Evaluation of Dupilumab in Patients With Asthma (TRAVERSE) study (NCT02134028), were included. This prespecified analysis evaluated long-term efficacy in patient populations identified by baseline type 2 biomarker level. End points were annualized exacerbation rate (AER) and change from baseline in pre-BD FEV1 (L), asthma control (5-item Asthma Control Questionnaire), and asthma-related quality of life (Asthma Quality of Life Questionnaire).
Results
A total of 663 patients were included. AER was 1.72 to 2.24 at QUEST baseline in dupilumab groups across type 2 populations. AER decreased in populations with elevated type 2 biomarkers to 0.36 to 0.49 during QUEST’s 52-week treatment period, which was sustained over 96 weeks in TRAVERSE. In patients with low type 2 biomarker levels, there was no clinically meaningful AER reduction in QUEST or TRAVERSE, but rates remained below parent study baseline. Similar trends were seen with improvements in pre-BD FEV1, 5-item Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire; greatest improvements were seen in groups with one or more elevated type 2 biomarker.
Intrepretation
This study suggests that long-term dupilumab treatment results in sustained and clinically meaningful efficacy in patients with moderate-to-severe type 2 asthma characterized by elevated blood eosinophil count and/or fractional exhaled nitric oxide.
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