杜匹单抗对以血液嗜酸性粒细胞和呼出一氧化氮为表型的中重度哮喘的长期疗效

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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本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

Clinical Trial Registration

ClinicalTrials.gov; No.: NCT02134028; URL: www.clinicaltrials.gov
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