Effect of monoclonal antibody drug therapy on mucosal biomarkers in airway disease: A systematic review

Sophie Walter; Jacqueline Ho; Raquel Alvarado; Janet Rimmer; Raewyn Campbell; Larry Kalish; Raymond Sacks; Richard J Harvey

doi:10.1111/cea.13721

Effect of monoclonal antibody drug therapy on mucosal biomarkers in airway disease: A systematic review

Clin Exp Allergy. 2020 Nov;50(11):1212-1222. doi: 10.1111/cea.13721. Epub 2020 Sep 9.

Authors

Sophie Walter¹, Jacqueline Ho¹, Raquel Alvarado¹, Janet Rimmer^{1

2

3}, Raewyn Campbell^{1

4

5}, Larry Kalish^{1

6}, Raymond Sacks^{1

5

6}, Richard J Harvey^{1

5}

Affiliations

¹ Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, New South Wales, Australia.
² Woolcock Institute, University of Sydney, Sydney, New South Wales, Australia.
³ Faculty of Medicine, Notre Dame University, Sydney, New South Wales, Australia.
⁴ Department of Otolaryngology Head and Neck Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
⁵ Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
⁶ Department of Otolaryngology, Head and Neck Surgery, Concord General Hospital, University of Sydney, Sydney, New South Wales, Australia.

PMID: 32808380
DOI: 10.1111/cea.13721

Abstract

Background: Monoclonal antibody therapies have a growing role in treating refractory airway disease.

Objective: The review aimed to summarize the response of respiratory mucosa to monoclonal antibody treatments in inflammatory airway conditions.

Design: We conducted a systematic review including risk of bias assessment.

Data sources: MEDLINE, EMBASE and PubMed from 1 January 2000 to 16 November 2019 were searched.

Eligibility criteria: Eligible studies assessed the immunological and histological response of airway mucosa to monoclonal antibody therapy compared with baseline or a comparison group in patients with respiratory diseases (asthma, chronic rhinosinusitis and allergic rhinitis). Any prospective interventional studies, including randomized controlled trials (RCTs) and single-arm trials, were eligible.

Results: There were 4195 articles screened, and full-text analysis produced n = 11 studies with extractable data. Nine were RCTs, and two were single-arm trials. These studies focused on asthma (n = 9 articles), chronic rhinosinusitis (n = 1) and allergic rhinitis (n = 1). Five monoclonal antibody drugs were assessed (omalizumab, mepolizumab, dupilumab, benralizumab and tralokinumab). Risk of bias was low (n = 6) or unclear (n = 3) in the RCTs and moderate in the single-arm trials. Omalizumab reduced the mucosal concentration of its target, IgE. Dupilumab reduced the concentration of one of its targets, IL-13, but not IL-4. Omalizumab, mepolizumab and benralizumab reduced tissue eosinophil cell density. Dupilumab decreased mucosal eosinophil granule proteins. Tralokinumab did not affect airway mucosa.

Conclusions: Knowledge of the expected biological response of monoclonal antibody therapy on biomarkers in disease tissue provides an important supplement to data about clinical outcomes. An understanding of the biological effect is essential to identify likely responders, reasons for treatment failure and necessary adjustments to monoclonal antibody treatment. Further investigation into the effect of monoclonal antibody therapy on disease mucosa and more precise endotyping are required to move closer to achieving personalized medicine.

Keywords: ENT; asthma; biomarker; monoclonal antibody; mucosa; rhinitis.

Publication types

Systematic Review

MeSH terms

Adult
Antibodies, Monoclonal / adverse effects
Antibodies, Monoclonal / therapeutic use*
Biomarkers / metabolism
Female
Humans
Immunity, Mucosal / drug effects*
Male
Middle Aged
Respiratory Mucosa / drug effects*
Respiratory Mucosa / immunology
Respiratory Mucosa / metabolism
Respiratory System Agents / adverse effects
Respiratory System Agents / therapeutic use*
Respiratory Tract Diseases / drug therapy*
Respiratory Tract Diseases / immunology
Respiratory Tract Diseases / metabolism
Treatment Outcome
Young Adult

Substances

Antibodies, Monoclonal
Biomarkers
Respiratory System Agents