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 nonallergen-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-allergenspecific 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.

Efficacy of Biologics in Patients with Allergic Severe Asthma, Overall and by Blood Eosinophil Count: A Literature Review

“…Finally, tezepelumab (anti-TSLP) has broad suppressive effects on type 2 inflammatory pathways, reducing the activity of IL-4, IL-5 and IL-13, as evidenced by reductions in blood and airway eosinophil counts, and FeNO and serum total IgE levels [ 10 , 11 ]. Tezepelumab has also been shown to reduce airway hyperresponsiveness [ 12 , 13 ], likely through type 2-dependent and -independent effects on airway smooth muscle and mast cell activation [ 39 – 41 ]. In addition to varying mechanisms of action of the biologics discussed, differences in study design, study populations and inclusion/exclusion criteria between trials could also contribute to the observed differences in AAER reductions.…”

Personalized and Precision Medicine in Asthma and Eosinophilic Esophagitis: The Role of T2 Target Therapy

“…The only other drug, which is currently not marketed for asthma, that achieved the result of reducing AHR was etanercept in one study. In the end, the only two drugs that are currently available for asthma and able to reduce AHR are tezepelumab and omalizumab [ 93 ].…”