Effect of Biologic Therapies on Airway Hyperresponsiveness and Allergic Response: A Systematic Literature Review

Abstract

Background: 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; asthma; biologic; randomized placebo-controlled trial; systematic review.

Figure 1

PRISMA flow diagram summarizing the selection process for publications included in the review.

Figure 2

Summary of included studies of biologic therapies and their effects on AHR in asthma. ↓Indicates that the biologic agent significantly reduced the AHR and significant results are highlighted by bolded text; ↔Indicates that the biologic therapy had no effect on the AHR. NS (NR) indicates when a p value was non-significant, but the value was not reported. ^ap values as reported in the publications cited. ^bAHR was the primary outcome of the study. ^cReduction in AHR to AMP at week 4 but not at week 12. ^dPatients with refractory asthma who participated in the crossover part of the study.

Figure 3

Summary of included studies of biologic therapies and their effects on the EAR and LAR in asthma. ↓Indicates that the biologic agent significantly reduced the EAR or LAR and significant results are highlighted by bolded text; ↔Indicates that the biologic therapy had no effect on the EAR or LAR. NS (NR) indicates when a p value was non-significant but the value was not reported. ^ap values as reported in the publications cited.^bGrouped according to screening IgE levels; group 1: 30–300 IU/mL (low IgE); group 2: 700–2000 IU/mL (high IgE). ^cReduction at day 14 but not at day 35.