Benralizumab
Benralizumab is a humanized, afucosylated IgG1-κ mAb that targets the α subunit of the IL-5 receptor (IL-5Rα) and it binds with high affinity to the main Fc receptor for IgG expressed by natural killer (NK) cells, macrophages and neutrophils, which results in eosinophil apoptosisvia antibody-dependent cell-mediated cytotoxicity160. Several studies have demonstrated that benralizumab administration leads to subjective and functional clinical improvement in patients with SEA. RCTs, reported an improvement in FEV1 at 12 weeks from the beginning of treatment 161-163. A post-hoc analysis conducted on SIROCCO and CALIMA data further documented that benralizumab promoted functional improvement even in patients with fixed obstruction, an alteration found in approximately 16% of patients with severe asthma164. A recent study extended the previous results by showing that benralizumab caused a rapid (4 weeks) improvement in FEV1, which increased after 12 weeks and persisted throughout the period (24 weeks) of observation 163.
Cachi and collaborators evaluated the effects of benralizumab on airway remodeling examining biopsies from patients with SEA165. Benralizumab reduced the number of eosinophils in the bronchial lamina propria and ASM mass compared to placebo. In the benralizumab group, there were no significant changes in the number of myofibroblasts compared to the control group. The effects of benralizumab on ASM mass were attributed to an indirect effect mediated by the depletion of local TGF-β1+ eosinophils in the bronchial lamina propria.
Pelaia and collaborators emphasized the clinical efficacy of benralizumab in terms of lung function in real life after the first administration of this mAb166. Padilla-Galoet al. reported an improvement in FEV1 after three months of treatment with benralizumab, which lasted up to six months 167. Similar results were obtained in a retrospective study168. The authors ascribed the rapid improvement of lung function to the early effects of the mAb on peripheral blood and bronchial eosinophils. Although these observations were obtained in small cohorts of patients, they emphasize that the improvement caused by benralizumab on lung function observed in real life is more evident compared to certain RCTs92, 161, 162. Finally, clinical trials (NCT04365205, NCT03953300) are evaluating the effects of benralizumab on airway remodeling.