PMID- 37692126
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231004
IS  - 1178-6965 (Print)
IS  - 1178-6965 (Electronic)
IS  - 1178-6965 (Linking)
VI  - 16
DP  - 2023
TI  - Tezepelumab Efficacy in Patients with Severe, Uncontrolled Asthma with Comorbid 
      Nasal Polyps in NAVIGATOR.
PG  - 915-932
LID - 10.2147/JAA.S413064 [doi]
AB  - PURPOSE: Tezepelumab, a human monoclonal antibody, blocks thymic stromal 
      lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced 
      annualized asthma exacerbation rates (AAERs) versus placebo, irrespective of 
      baseline disease characteristics, and improved lung function and symptom control 
      versus placebo in adults and adolescents with severe, uncontrolled asthma. We 
      assessed the efficacy of tezepelumab in patients with severe asthma with or 
      without nasal polyps (NPs) in the 2 years before randomization in NAVIGATOR. 
      METHODS: Patients with severe asthma (N=1059) were randomized (1:1) and received 
      tezepelumab 210 mg or placebo every 4 weeks subcutaneously for 52 weeks. 
      Prespecified exploratory analyses included: AAER over 52 weeks and changes from 
      baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 second, 
      Sino-Nasal Outcome Test (SNOT)-22 scores, and asthma control and health-related 
      quality life (HRQoL) outcomes in NP subgroups. Changes from baseline in 
      fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total 
      immunoglobulin E (IgE), eosinophil-derived neurotoxin (EDN), matrix 
      metalloproteinase-10 (MMP-10), and serum interleukin (IL)-5, IL-6, IL-8 and IL-13 
      were assessed (post hoc). RESULTS: Tezepelumab reduced the AAER over 52 weeks 
      versus placebo by 85% (95% confidence interval [CI]: 72, 92; n=118) and 51% (95% 
      CI: 40, 60; n=941) in patients with and without NPs, respectively. At week 52, 
      tezepelumab improved lung function, asthma control and HRQoL versus placebo in 
      patients with and without NPs. Tezepelumab reduced SNOT-22 total scores 
      (least-squares mean difference versus placebo [95% CI]) in patients with NPs at 
      28 weeks (-12.57 points [-19.40, -5.73]) and 52 weeks (-10.58 points [-17.75, 
      -3.41]). At week 52, tezepelumab reduced blood eosinophil counts and FeNO, IgE, 
      IL-5, IL-13, EDN and MMP-10 levels versus placebo, irrespective of NP status. 
      CONCLUSION: Tezepelumab resulted in clinically meaningful improvements in 
      sino-nasal symptoms and asthma outcomes in patients with severe asthma with 
      comorbid NPs.
CI  - (c) 2023 Laidlaw et al.
FAU - Laidlaw, Tanya M
AU  - Laidlaw TM
AUID- ORCID: 0000-0001-6709-9795
AD  - Jeff and Penny Vinik Center for Allergic Diseases Research, Division of Allergy 
      and Clinical Immunology, Brigham and Women's Hospital, Boston, MA, USA.
AD  - Department of Medicine, Harvard Medical School, Boston, MA, USA.
FAU - Menzies-Gow, Andrew
AU  - Menzies-Gow A
AD  - Royal Brompton and Harefield Hospitals, School of Immunology and Microbial 
      Sciences, King's College London, London, UK.
FAU - Caveney, Scott
AU  - Caveney S
AD  - Global Development, Inflammation, R&D, Amgen, Thousand Oaks, CA, USA.
FAU - Han, Joseph K
AU  - Han JK
AD  - Department of Otolaryngology, Head and Neck Surgery, Eastern Virginia Medical 
      School, Norfolk, VA, USA.
FAU - Martin, Nicole
AU  - Martin N
AD  - Biometrics, Late-Stage Development, Respiratory and Immunology, 
      BioPharmaceuticals R&D, AstraZeneca, Waltham, MA, USA.
AD  - Cytel Inc, Waltham, MA, USA.
FAU - Israel, Elliot
AU  - Israel E
AUID- ORCID: 0000-0002-2470-856X
AD  - Divisions of Pulmonary and Critical Care Medicine and Allergy and Clinical 
      Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 
      USA.
FAU - Lee, Jason K
AU  - Lee JK
AD  - Evidence Based Medical Educator Inc., Toronto, ON, Canada.
AD  - Toronto Allergy and Asthma Clinic, Toronto, ON, Canada.
FAU - Llanos, Jean-Pierre
AU  - Llanos JP
AD  - Global Medical Affairs, Amgen, Thousand Oaks, CA, USA.
FAU - Martin, Neil
AU  - Martin N
AD  - Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, 
      UK.
AD  - University of Leicester, Leicester, UK.
FAU - Megally, Ayman
AU  - Megally A
AD  - Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, 
      AstraZeneca, Gaithersburg, MD, USA.
FAU - Parikh, Bhavini
AU  - Parikh B
AUID- ORCID: 0009-0006-7374-1274
AD  - Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, 
      AstraZeneca, Gaithersburg, MD, USA.
FAU - Vong, Sylvia
AU  - Vong S
AD  - Translational Science and Experimental Medicine, Early Respiratory and 
      Immunology, AstraZeneca, Gaithersburg, MD, USA.
FAU - Welte, Tobias
AU  - Welte T
AUID- ORCID: 0000-0002-9947-7356
AD  - Department of Respiratory Medicine and German Center for Lung Research, Hannover 
      Medical School, Hannover, Germany.
FAU - Corren, Jonathan
AU  - Corren J
AD  - David Geffen School of Medicine, University of California, Los Angeles (UCLA), 
      Los Angeles, CA, USA.
LA  - eng
PT  - Journal Article
DEP - 20230904
PL  - New Zealand
TA  - J Asthma Allergy
JT  - Journal of asthma and allergy
JID - 101543450
EIN - J Asthma Allergy. 2023 Sep 27;16:1053-1054. PMID: 37791042
PMC - PMC10488831
OTO - NOTNLM
OT  - SNOT-22
OT  - chronic rhinosinusitis
OT  - nasal polyps
OT  - thymic stromal lymphopoietin
COIS- Tanya M Laidlaw has served on scientific advisory boards for Amgen, GSK, 
      Regeneron and Sanofi. Andrew Menzies-Gow is an employee of AstraZeneca and may 
      own stock or stock options in AstraZeneca; has attended advisory board meetings 
      for AstraZeneca, GSK, Novartis, Regeneron, Sanofi and Teva Pharmaceuticals; has 
      received speaker fees from AstraZeneca, Novartis, Sanofi and Teva 
      Pharmaceuticals; has participated in research with AstraZeneca, for which his 
      institution has been remunerated; has attended international conferences with 
      Teva Pharmaceuticals; and has consultancy agreements with AstraZeneca and Sanofi. 
      Joseph K Han has received consultancy fees from AstraZeneca, Genentech, Gossamer 
      Bio, GSK, Novartis, Regeneron and Sanofi-Genzyme. Elliot Israel has served as a 
      consultant to and received personal fees from 4D Pharma, AB Science, the Allergy 
      and Asthma Network, Amgen, AstraZeneca, Avillion, Biometry, Cowen, Equillium, 
      Genentech, GSK, Merck, National Heart, Lung and Blood Institute, Novartis, Pneuma 
      Respiratory, PPS Health, Regeneron Pharmaceuticals, Sanofi, Sienna 
      Biopharmaceuticals, Teva Pharmaceuticalsand Westchester Medical Center; has 
      received non-financial support from Circassia, Teva Pharmaceuticals and Vorso 
      Corp; and has received clinical research grants from AstraZeneca, Avillion, 
      Genentech, Gossamer Bio, National Institutes of Health (NIH), Novartis, 
      Patient-Centered Outcomes Research Institute and Sanofi; royalties or licenses 
      from UpToDate - Wolters Kluwer; stock options from Nesos Corp; study drug for NIH 
      PrecISE trial for CSL Behring, Laurel Pharmaceuticals, Om Pharmaceuticals, Nestle 
      and Sun Pharmaceuticals; study drug for NIH IDEA for Sanofi-Regeneron. Jason K 
      Lee has received research support from ALK, AstraZeneca Bausch Health, Genentech, 
      GSK, Meda, Medexus, Miravo, Novartis, Regeneron, Roche, Sanofi-Genzyme and 
      Takeda; has received fees for speakers' bureau from Aralez, AstraZeneca, GSK, 
      Medexus, Merck, Mylan, Novartis and Sanofi-Genzyme; and has received consultancy 
      fees from and is an advisory committee member of AstraZeneca, GSK, Medexus, 
      Novartis, Regeneron and Sanofi-Genzyme. Tobias Welte has received fees for 
      lectures and/or advisory board meetings from AstraZeneca, Berlin-Chemie, 
      Boehringer Ingelheim, Chiesi, GSK, MSD, Novartis, Roche, Pfizer and Sanofi 
      Aventis; grants from the German Ministry of Research and Education, AstraZeneca 
      and GSK. Jonathan Corren has received grants and personal fees from AstraZeneca, 
      Genentech, RAPT, Regeneron and Vectura; and has received grants from Optinose, 
      Pulmatrix, Sanofi and Teva Pharmaceuticals. Scott Caveney and Jean-Pierre Llanos 
      are employees of Amgen and own stock in Amgen. Nicole Martin, Neil Martin, Ayman 
      Megally, Bhavini Parikh and Sylvia Vong are employees of AstraZeneca and may own 
      stock or stock options in AstraZeneca. The authors report no other conflicts of 
      interest in this work.
EDAT- 2023/09/11 06:43
MHDA- 2023/09/11 06:44
PMCR- 2023/09/04
CRDT- 2023/09/11 04:33
PHST- 2023/04/11 00:00 [received]
PHST- 2023/08/07 00:00 [accepted]
PHST- 2023/09/11 06:44 [medline]
PHST- 2023/09/11 06:43 [pubmed]
PHST- 2023/09/11 04:33 [entrez]
PHST- 2023/09/04 00:00 [pmc-release]
AID - 413064 [pii]
AID - 10.2147/JAA.S413064 [doi]
PST - epublish
SO  - J Asthma Allergy. 2023 Sep 4;16:915-932. doi: 10.2147/JAA.S413064. eCollection 
      2023.