Exacerbation and glucocorticoid toxicity profile in patients receiving mepolizumab for severe eosinophilic asthma

Student thesis: Doctoral ThesisDoctor of Philosophy


The treatment of patients with severe eosinophilic asthma has been transformed with the arrival of biological drugs targeting the type 2 cytokine pathway. One of these drugs is mepolizumab, a humanised monoclonal antibody against the eosinophil activating cytokine, interleukin (IL)-5, has consistently been shown to lead to a 50% reduction in exacerbation rate, when compared with placebo, and facilitates the weaning of maintenance oral corticosteroids (OCS) in patients with severe eosinophilic asthma.

This works seeks to address two questions that arise from treatment with this novel monoclonal antibody:

1. What is the inflammatory phenotype and the physiological characteristics of the residual asthma exacerbations that occur in patients with severe eosinophilic asthma treated with anti-IL5 monoclonal antibodies?

2. To quantify toxicity associated with OCS treatment in severe eosinophilic asthmatics, and assess change in OCS-related toxicity after 1 year's treatment with mepolizumab and subsequent reduction in OCS, both through weaning of maintenance OCS and reduction in OCS for asthma exacerbations.
Date of AwardDec 2022
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SponsorsUnited Kingdom Medical Research Council Refractory Asthma Stratification Programme
SupervisorLiam Heaney (Supervisor) & Lorcan McGarvey (Supervisor)


  • Asthma
  • eosinophilic
  • T2 high
  • monoclonal antibodies

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