Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY

被引:34
作者
Corren, Jonathan [1 ]
Garcia Gil, Esther [2 ]
Griffiths, Janet M. [3 ]
Parnes, Jane R. [4 ]
van der Merwe, Rene [5 ]
Salapa, Kinga [6 ]
O'Quinn, Sean [7 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA
[2] AstraZeneca, BioPharmaceut Res & Dev, Global Med Resp, Barcelona, Spain
[3] AstraZeneca, Translat Sci & Expt Med, Res & Early Dev, Resp & Immunol,BioPharmaceut Res & Dev, Gaithersburg, MD USA
[4] Amgen Inc, Thousand Oaks, CA USA
[5] AstraZeneca, Cambridge, England
[6] AstraZeneca, BioPharmaceut Res & Dev, Late Resp & Immunol, Biometr, Warsaw, Poland
[7] AstraZeneca, BioPharmaceut Res & Dev, Resp & Immunol, Gaithersburg, MD USA
关键词
THYMIC STROMAL LYMPHOPOIETIN; QUALITY-OF-LIFE; HUMAN EPITHELIAL-CELLS; EXPRESSION; PLACEBO; EXACERBATIONS; INFLAMMATION; VALIDATION; MANAGEMENT; CHEMOKINES;
D O I
10.1016/j.anai.2020.10.008
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Patients with severe, uncontrolled asthma experience frequent exacerbations and hospitalization, leading to poor health-related quality of life. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced exacerbations by up to 71% and improved lung function, asthma control, and health-related quality of life vs placebo. Objective: This analysis further assessed the impact of tezepelumab on patient-reported outcomes (PROs) in PATHWAY. Methods: Adults with severe, uncontrolled asthma were randomized to subcutaneous tezepelumab (70 mg every 4 weeks, 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. PROs were assessed using the asthma control questionnaire-6 (ACQ-6) and the asthma quality of life questionnaire (standardized) for patients aged 12 years or older (AQLQ[S]+12). The proportions of responders (defined by improvements of similar to 0.5 in ACQ-6 or AQLQ(S)+12 scores) and patients whose asthma was well-controlled, partially-controlled, or uncontrolled in the tezepelumab and placebo groups were identified. The Asthma Daily Diary questionnaire was used to assess changes in overall symptom severity. Results: Overall, 550 patients were randomized. Up to 82% and 77% of tezepelumab-treated patients were ACQ-6 and AQLQ(S)+12 responders, respectively, compared with 70% and 64% of placebo-treated patients, respectively. The proportions of patients with well-controlled or partially-controlled asthma were higher in the tezepelumab-treated group than in the placebo group. In addition, tezepelumab improved the overall symptom severity. Conclusion: Tezepelumab treatment improved PROs vs placebo, as indicated by the higher proportion of ACQ-6 and AQLQ(S)+12 responders and improvements in symptom severity in the tezepelumab dose groups. These data further support the benefits of tezepelumab in patients with severe, uncontrolled asthma. (C) 2020 American College of Allergy, Asthma & Immunology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
引用
收藏
页码:187 / 193
页数:7
相关论文
共 36 条
[1]   Thymic stfomal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells [J].
Allakhverdi, Zoulfia ;
Comeau, Michael R. ;
Jessup, Heidi K. ;
Yoon, Bo-Rin Park ;
Brewer, Avery ;
Chartier, Suzanne ;
Paquette, Nicole ;
Ziegler, Steven F. ;
Sarfati, Marika ;
Delespesse, Guy .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (02) :253-258
[2]  
[Anonymous], 2006, HEALTH QUAL LIFE OUT, DOI DOI 10.1186/1477-7525-4-79
[3]  
Castro M, 2015, LANCET RESP MED, V3, P355, DOI [10.1016/S2213-2600(15)00042-9, 10.1016/S2213-2600(15)00119-8]
[4]   Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study [J].
Castro, Mario ;
Wenzel, Sally E. ;
Bleecker, Eugene R. ;
Pizzichini, Emilio ;
Kuna, Piotr ;
Busse, William W. ;
Gossage, David L. ;
Ward, Christine K. ;
Wu, Yanping ;
Wang, Bing ;
Khatry, Deepak B. ;
van der Merwe, Rene ;
Kolbeck, Roland ;
Molfino, Nestor A. ;
Raible, Donald G. .
LANCET RESPIRATORY MEDICINE, 2014, 2 (11) :879-890
[5]   Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma A Multicenter, Randomized, Double-Blind, Sham-Controlled Clinical Trial [J].
Castro, Mario ;
Rubin, Adalberto S. ;
Laviolette, Michel ;
Fiterman, Jussara ;
Lima, Marina De Andrade ;
Shah, Pallav L. ;
Fiss, Elie ;
Olivenstein, Ronald ;
Thomson, Neil C. ;
Niven, Robert M. ;
Pavord, Ian D. ;
Simoff, Michael ;
Duhamel, David R. ;
McEvoy, Charlene ;
Barbers, Richard ;
ten Hacken, Nicolaas H. T. ;
Wechsler, Michael E. ;
Holmes, Mark ;
Phillips, Martin J. ;
Erzurum, Serpil ;
Lunn, William ;
Israel, Elliot ;
Jariour, Nizar ;
Kraft, Monica ;
Shargill, Narinder S. ;
Quiring, John ;
Berry, Scott M. ;
Cox, Gerard .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2010, 181 (02) :116-124
[6]  
Chastek Benjamin, 2016, J Manag Care Spec Pharm, V22, P848, DOI 10.18553/jmcp.2016.22.7.848
[7]   Asthma control, severity, and quality of life: Quantifying the effect of uncontrolled disease [J].
Chen, Hubert ;
Gould, Michael K. ;
Blanc, Paul D. ;
Miller, Dave P. ;
Kamath, Tripthi V. ;
Lee, June H. ;
Sullivan, Sean D. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 120 (02) :396-402
[8]   International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma [J].
Chung, Kian Fan ;
Wenzel, Sally E. ;
Brozek, Jan L. ;
Bush, Andrew ;
Castro, Mario ;
Sterk, Peter J. ;
Adcock, Ian M. ;
Bateman, Eric D. ;
Bel, Elisabeth H. ;
Bleecker, Eugene R. ;
Boulet, Louis-Philippe ;
Brightling, Christopher ;
Chanez, Pascal ;
Dahlen, Sven-Erik ;
Djukanovic, Ratko ;
Frey, Urs ;
Gaga, Mina ;
Gibson, Peter ;
Hamid, Qutayba ;
Jajour, Nizar N. ;
Mauad, Thais ;
Sorkness, Ronald L. ;
Teague, W. Gerald .
EUROPEAN RESPIRATORY JOURNAL, 2014, 43 (02) :343-373
[9]   Asthma outcomes: Composite scores of asthma control [J].
Cloutier, Michelle M. ;
Schatz, Michael ;
Castro, Mario ;
Clark, Noreen ;
Kelly, H. William ;
Mangione-Smith, Rita ;
Sheller, James ;
Sorkness, Christine ;
Stoloff, Stuart ;
Gergen, Peter .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2012, 129 (03) :S24-S33
[10]  
Committee for Medicinal Products for Human Use, 2005, REFLECTION PAPER REG