Journal of Asthma and Allergy (Jul 2023)
Effect of Biologic Therapies on Airway Hyperresponsiveness and Allergic Response: A Systematic Literature Review
Abstract
Joseph D Spahn,1 Christopher E Brightling,2 Paul M O’Byrne,3 Lisa J Simpson,4 Nestor A Molfino,5 Christopher S Ambrose,6 Neil Martin,2,7 Teal S Hallstrand8 1Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Wilmington, DE, USA; 2Institute for Lung Health, NIHR Leicester Biomedical Research Centre, Department of Respiratory Sciences, University of Leicester, Leicester, UK; 3Firestone Institute for Respiratory Health, St Joseph’s Hospital and Department of Medicine, McMaster University, Hamilton, Ontario, Canada; 4PharmaGenesis London, London, UK; 5Global Development, Amgen, Thousand Oaks, CA, USA; 6Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 7Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 8Division of Pulmonary, Critical Care and Sleep Medicine, and the Center for Lung Biology, Department of Medicine, University of Washington, Seattle, WA, USACorrespondence: Joseph D Spahn, AstraZeneca, 1800 Concord Pike, Wilmington, DE, 19803, USA, Tel +1 303-886-5257, Email [email protected]: Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying disease pathophysiology. This review summarizes the available evidence regarding the effects of biologics on allergen-specific and non-allergen-specific airway responses in patients with asthma.Methods: We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including risk-of-bias assessment. PubMed and Ovid were searched for studies published between January 1997 and December 2021. Eligible studies were randomized, placebo-controlled trials that assessed the effects of biologics on AHR, early allergic response (EAR) and/or late allergic response (LAR) in patients with asthma.Results: Thirty studies were identified for inclusion. Bronchoprovocation testing was allergen-specific in 18 studies and non-allergen-specific in 12 studies. Omalizumab reduced AHR to methacholine, acetylcholine or adenosine monophosphate (3/9 studies), and reduced EAR (4/5 studies) and LAR (2/3 studies). Mepolizumab had no effect on AHR (3/3 studies), EAR or LAR (1/1 study). Tezepelumab reduced AHR to methacholine or mannitol (3/3 studies), and reduced EAR and LAR (1/1 study). Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR to methacholine (1/2 studies). No effects were observed for lebrikizumab, tocilizumab, efalizumab, IMA-638 and anti-OX40 ligand on AHR, EAR or LAR; benralizumab on LAR; tralokinumab on AHR; and Ro-24-7472 on AHR or LAR (all 1/1 study each). No dupilumab or reslizumab studies were identified.Conclusion: Omalizumab and tezepelumab reduced EAR and LAR to allergens. Tezepelumab consistently reduced AHR to methacholine or mannitol. These findings provide insights into AHR mechanisms and the precise effects of asthma biologics. Furthermore, findings suggest that tezepelumab broadly targets allergen-specific and non-allergic forms of AHR, and the underlying cells and mediators involved in asthma.Keywords: airway hyperresponsiveness, allergic response, biologic, systematic review, asthma, randomized placebo-controlled trial
