DOI: 10.25934/pr00007274
title: Efficacy comparision of biologics (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) in treatment of severe eosinophilic asthma -- a network meta-analysis

description: Asthma affects 1% - 18% of population worldwide, and 17% of those have difficult-to-treat asthma. These patients suffer from poor control of symptoms even if they have received high intensity of treatments. Asthma is a complex disease, which means multiple mechanisms might contribute to its pathogenesis. Based on their clinical and pathophysiological characters, asthma patients can be divided into several different types, and the most common type is allergic asthma. Eosinophil, which is a type of white blood cell (leukocytes) that are secreted in response to allergic reactions, skin conditions and parasitic and fungal infections, are prominent pathogenic cells involved in the allergic asthma. Increased blood eosinophils are related to frequent asthma exacerbations and disease severity and therefore used to guide treatment decisions. The elevated blood eosinophils are associated with increased interleukin (IL)-5 production. IL-5is a type of cytokines, which are tiny proteins secreted by both immune and non-immune cells to bind to their receptors and trigger responses in the receiving cells. IL-5 is often co-expressed with other type 2 (T2) cytokines including IL-4 and IL-13 and associated with increased immunoglobulin (a protein with antibody activityplaying essential role in the immune response)-E production in atopic individuals.

For a certain cluster of difficult-to-treat asthma and severe asthma patients, monoclonal antibodies which have high degree of specificity (mono-specificity) for a certain type of antigen or epitope, termed as biologics, can be added to their management. Several biologics have been proved effective in randomized clinical trials (RCTs, one of the most powerful clinical research types, in which individuals receive two or more interventions in random order), such as mepolizumab (anti–IL-5 monoclonal antibodies), reslizumab (anti–IL-5 monoclonal antibodies), benralizumab (anti-IL-5Rα monoclonal antibodies), dupilumab (anti-IL-4Rα monoclonal antibodies) and omalizumab (anti-IgE antibody). However, no head-to-head comparisons have been conducted between these drugs, leaving a question of the choice of biologics when a patient is eligible for more than one biologic. Therefore, we ought to compare the efficacy of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab in the treatment of severe eosinophilic asthma by using a method of network meta-analysis (a technique for comparing multiple treatments simultaneously in a single analysis by combining direct and indirect evidence within a network of randomized controlled trials). In particular, we ought to know whether the treatment efficacy vary in asthma patients with different level of blood eosinophils. To conduct the network meta-analysis, we will search online databases including PubMed, Embase, Cochrane to retrieve eligible RCT studies by establishing suitable inclusion and exclusion criteria. Then we will extract the data needed for further network meta-analysis by using Microsoft Office 2016. We choose network meta-analysis because it combines direct and indirect estimates across a network of interventions in a single analysis.