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.