Dupilumab Efficacy in Uncontrolled, Moderate-to-Severe Asthma with Self-Reported Chronic Rhinosinusitis

被引：51

作者：

Maspero, Jorge F. ^{[1
]}

Katelaris, Constance H. ^{[2
,3
]}

Busse, William W. ^{[4
]}

Castro, Mario ^{[5
]}

Corren, Jonathan ^{[6
]}

Chipps, Bradley E. ^{[7
]}

Peters, Anju T. ^{[8
,9
]}

Pavord, Ian D. ^{[10
]}

Ford, Linda B. ^{[11
]}

Sher, Lawrence ^{[12
]}

Rabe, Klaus F. ^{[13
,14
,15
,16
]}

Rice, Megan S. ^{[17
]}

Rowe, Paul ^{[18
]}

Lu, Yufang ^{[19
]}

Harel, Sivan ^{[19
]}

Jagerschmidt, Alexandre ^{[20
]}

Khan, Asif H. ^{[20
]}

Kamat, Siddhesh ^{[19
]}

Pirozzi, Gianluca ^{[18
]}

Amin, Nikhil ^{[19
]}

Ruddy, Marcella ^{[19
]}

Graham, Neil M. H. ^{[19
]}

Mannent, Leda P. ^{[20
]}

Teper, Ariel ^{[18
]}

机构：

[1] Fdn CIDEA, Paraguay 2035,C1121ABE, Buenos Aires, DF, Argentina

[2] Campbelltown Hosp, Campbelltown, NSW, Australia

[3] Western Sydney Univ, Sydney, NSW, Australia

[4] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA

[5] Washington Univ, Sch Med, St Louis, MO USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[7] Capital Allergy & Resp Dis Ctr, Sacramento, CA USA

[8] Northwestern Univ, Div Allergy Immunol, Feinberg Sch Med, Chicago, IL 60611 USA

[9] Northwestern Univ, Sinus & Allergy Ctr, Feinberg Sch Med, Chicago, IL 60611 USA

[10] Univ Oxford, Oxford, England

[11] Asthma & Allergy Ctr, Bellevue, NE USA

[12] Peninsula Res Associates, Rolling Hills Estates, CA USA

[13] LungenClin Grosshansdorf, Grosshansdorf, Germany

[14] German Ctr Lung Res DZL, Grosshansdorf, Germany

[15] Christian Albrechts Univ Kiel, Kiel, Germany

[16] German Ctr Lung Res DZL, Kiel, Germany

[17] Sanofi Genzyme, Cambridge, MA USA

[18] Sanofi, Bridgewater, NJ USA

[19] Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA

[20] Sanofi, Chilly Mazarin, France

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE | 2020年 / 8卷 / 02期

关键词：

Chronic rhinosinusitis; Dupilumab; Efficacy; Safety; Asthma; Anti-IL-4; Anti-IL-13; INFLAMMATORY PATTERNS; EOSINOPHILIC ASTHMA; NASAL POLYPS; PLACEBO; HUMANIZATION; EXPRESSION; MANAGEMENT; PHASE-3; SAFETY; ADULTS;

D O I：

10.1016/j.jaip.2019.07.016

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

BACKGROUND: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13 signaling, key drivers of type 2 inflammation. In the phase 3 study (NCT02414854), add-on dupilumab 200mg/300mg every 2 weeks, versus placebo, significantly reduced severe asthma exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) and quality-of-life measures in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in those with a high baseline type 2 phenotype. OBJECTIVE: To assess the efficacy and safety of dupilumab in patients with uncontrolled, moderate-to-severe asthma with or without self-reported comorbid chronic rhinosinusitis (CRS or non-CRS). METHODS: Comorbid CRS was self-reported by patients using an e-diary. Annualized severe exacerbation rates, changes from baseline in pre- and post-bronchodilator FEV1, patient-reported outcomes, type 2 biomarkers, and safety were assessed. RESULTS: CRS was self-reported by 382 of 1902 (20.1%) patients. Dupilumab 200 mg/300 mg reduced annualized severe exacerbation rates by 63%/61%, respectively, in patients with CRS, and by 42%/40% in patients without CRS (all P < .001 vs placebo). Dupilumab also improved lung function and patient-reported asthma control and quality of life, and suppressed type 2 biomarkers versus placebo in both subgroups. Clinical responses were rapid, with near-maximal responses observed at the earliest measured time points and sustained at week 52. Improvements observed in the CRS subgroup were similar to or numerically greater than those in the non-CRS subgroup. CONCLUSION: Dupilumab showed efficacy and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma with or without CRS. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

引用

页码：527 / +

页数：22

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