Large reductions in exacerbation rates were observed compared to placebo, though only benralizumab was sufficiently powered (n = 2051) to demonstrate significantly decreased exacerbation rates in the subgroup analysis of IL-5 acting agents compared to placebo.Monoclonal antibodies such as mepolizumab, reslizumab and benralizumab have proven their benefit to reduce exacerbation rates in severe persistent eosinophilic asthma in the published trials.
IL-3-upregulated genes may provide a foundation for research into therapeutics for patients with eosinophilic asthma who do not respond to anti-IL-5 therapies.
Several monoclonal antibody therapies targeting interleukin (IL)-4/IL-13 and IL-5 cytokine pathways have been developed for the treatment of severe eosinophilic asthma.
<b>Areas covered</b>: In this review, we discuss the role and pathogenesis of IL-5 and eosinophils in asthma and rationale of antagonizing IL-5 in severe eosinophilic asthma.
We found that purified human eosinophils stimulated with IL-5 predominantly secreted CCL4 and that patients with EP had elevated CCL11 and CCL4 levels in BALF compared with samples from individuals without EP.
Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy.
Benralizumab, a humanized, anti-interleukin-5 (anti-IL-5) receptor α monoclonal antibody that directly and rapidly depletes eosinophils, has shown significant efficacy in reducing asthma exacerbations and improving lung function in moderate to severe eosinophilic asthma patients.
Mepolizumab, a humanized monoclonal antibody that neutralizes IL-5 and efficiently attenuates eosinophils, proved clinically effective in severe eosinophilic asthma but not in mild asthma.
Eosinophilic asthma is often due to a type-2 immune response and production of IL-5, which leads to eosinophilopiesis and recruitment of mature eosinophils in the airways.
Anti-IL-5/IL-5R biologics are indicated in patients with severe eosinophilic asthma and repetitive exacerbations, irrespective of the presence or absence of allergy.
Biologics targeting IL-5 and its receptor (first mepolizumab and subsequently, reslizumab and benralizumab), have been recently approved and used as add-on therapy for severe eosinophilic asthma resulting in a reduction in the circulating eosinophil count, improvement in lung function and exacerbation reduction in asthma patients.
This short review discusses recent studies of the effectiveness of the anti-IL-5 reslizumab in relation to the use of simple reproducible biomarkers in eosinophilic asthma.
In placebo-controlled trials, reslizumab, an anti-IL-5 monoclonal antibody, significantly reduced asthma exacerbations and improved lung function and asthma control in patients with eosinophilic asthma.
Since IL-5 plays an important role in the maturation, survival and migration of eosinophils, hence the pathogenesis of eosinophilic asthma, biotherapeutics targeting IL-5/IL-5Rα have been developed and/or marketed, including Mepolizumab, Reslizumab, and Benralizumab.
We also review the evidence to date regarding the efficacy of mepolizumab (an anti-IL-5 monoclonal antibody) in severe eosinophilic asthma and the smaller evidence base regarding its efficacy in EGPA, an indication for which it recently received U.S. Food and Drug Administration approval.
Mepolizumab is a humanized monoclonal antibody which targets interleukin-5 (IL-5) and is nowadays available in many countries for add-on biological therapy of severe eosinophilic asthma.
One notable exception is the targeting of eosinophilic airway inflammation with anti-IL-5, which has an acknowledged and important role in the treatment of severe eosinophilic asthma.
Within such a context, the anti-IL-5 monoclonal antibodies mepolizumab and reslizumab have been developed and approved for biological therapy of uncontrolled eosinophilic asthma.
Therefore, for uncontrolled patients with severe eosinophilic asthma, who are not fully responsive to corticosteroids, IL-5 represents a very important molecular target for add-on biological therapies.