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.