Findings from a literature review presented at the American Thoracic Society’s (ATS) International Conference 2022 provide insight into the mechanisms of airway hyperresponsiveness (AHR) in asthma and the clinical benefits of multiple biologic treatments.
Researchers searched MEDLINE for randomized, placebo-controlled clinical trials of biologics (approved, non-approved, and discontinued) used in the treatment of asthma that assessed allergic response or AHR. Overall, 177 full-text articles published between 1997 and 2021 were identified, of which 22 were included in the review. Data on early allergic responses (EAR), late allergic responses (LAR), and AHR were extracted, according to the study abstract.
“Airway inflammation plays an important role in the pathogenesis of AHR, and the effects of therapies on AHR type and severity provide information on the underlying biology of asthma,” wrote the review authors. “The objective of this literature review was to describe the available evidence regarding the effects of biologic treatments on AHR.”
More than 50% of the studies used allergen challenges to assess EAR, LAR, and the associated increase in AHR after specific allergen inhalation, while the remaining studies evaluated the effect of biologic therapy on nonspecific AHR via direct or indirect measures.
Across 6 studies, investigators noted that omalizumab reduced EAR, LAR, and AHR to methacholine or acetylcholine. Mepolizumab did not affect EAR or LAR, or AHR. In 1 study each, IMA-638, lebrikizumab, and tralokinumab had no effect on AHR.One study showed pitrakinra reduced LAR, with no effect on AHR. In another study, etanercept reduced AHR. One study concluded that benralizumab had no effect on LAR, and there were no studies identified that assessed AHR. In 1 study, efalizumab, tocilizumab, Ro-24-7472, and anti-OX40 ligand did not affect AHR. Across 3 studies, tezepelumab attenuated EAR and LAR, and AHR to methacholine and mannitol. No published studies were identified for dupilumab or reslizumab, authors noted.
“Across multiple biologics studied, reductions in both EAR and LAR to allergens were observed with omalizumab and tezepelumab. Tezepelumab also consistently attenuated nonspecific AHR to methacholine or mannitol,” concluded the team of researchers. “These findings provide further insight into the mechanisms of AHR and the clinical benefits of asthma biologics and suggest that tezepelumab may broadly target mediators or cells involved in asthma inflammation.”
Parvathy Sukumaran 
