Benralizumab
Benralizumab is a monoclonal antibody direct against the α-subunit of
the IL-5 receptor expressed on eosinophil and basophil, inhibiting the
signaling and inducing cytotoxicity. Benralizumab is approved by EMA for
adults and by FDA for adolescents with severe eosinophilic asthma.
Benralizumab is given subcutaneously at a dose of 30 mg every four weeks
for the first three doses and then 30 mg every eight weeks. Long-term
efficacy over one year has been demonstrated. Frequent adverse events
include headache and pharyngitis; anaphylaxis is rare. Benralizumab
induces eosinophilic depletion in blood, sputum, and airway mucosa. In a
trial of 1306 asthmatic adolescents and adults randomly assigned
to benralizumab
or placebo for 60 weeks, the annual exacerbation rate is reduced in the
benralizumab group (RR 0.64, 95% CI 0.49-0.85).9Several studies – lasting up to years - show similar significant
results. The glucocorticoid-sparing effect is examined in a 28-week
multicenter trial: the odds of reduction in the oral glucocorticoid dose
with benralizumab are 4.09 times that with placebo.10
Busse and colleagues indirectly compared the efficacy of mepolizumab,
benralizumab and reslizumab in patients aged 12 years or older with
severe eosinophilic asthma, when grouped by patients’ blood eosinophil
counts, which are known to influence treatment
effect.11 The study shows that mepolizumab reduces
exacerbations by 34%–45% versus benralizumab across subgroups, and by
45% versus reslizumab in the ≥400cells/µL subgroup. Moreover,
mepolizumab is more effective in asthma control. There are no critical
differences in lung function measured by change from baseline in
pre-bronchodilator FEV1.11
In summary, targeted therapies with anti-IL-5 or anti-IL-5Rα approved in
children include mepolizumab (>6 years) and benralizumab
(>12 years); reslizumab is today still off-label.
In case of severe refractory asthma, they offer a more personalized
add-on treatment that results effective for reducing exacerbations and
improves the asthma quality of life in the long-term.
For the management of eosinophilic esophagitis, the standard therapies
such as diet elimination or corticosteroids can give concerns in some
children, including lack of effectiveness, negative impact on the
quality of life, or significant toxicity. Biologics can be a new
strategy option, but more results collected specifically from pediatric
clinical trials are needed.
In conclusion, anti-IL-5 agents are safe and effective in a short- and
medium-term treatment of adult patients, whereas information for optimal
therapy duration and long-term use is still lacking. Moreover, further
researches are necessary for patients eligible for more than one
treatment to find the adequate drug for each case through an
evidence-based choice.12
Several studies about the efficacy and safety in pediatric patients are
currently ongoing.
It’s necessary to recruit large numbers of characterized children, with
a wide range of endotypes with associated biomarkers prospectively
measured, to predict the responders and compare the biologics.