Inflammation following mepolizumab and oral corticosteroids in asthma
Research type
Research Study
Full title
Persistence of inflammation and study of T2 pathways following inhibition of Interleukin-5 with Mepolizumab in severe eosinophilic asthma
IRAS ID
241305
Contact name
Rekha Chaudhuri
Contact email
Sponsor organisation
NHS Greater Glasgow and Clyde
Duration of Study in the UK
1 years, 3 months, 16 days
Research summary
In asthma, exacerbations are triggered by a blood cell called the eosinophil and the levels of this are controlled by a protein called Interleukin-5 [IL-5]. There is a new injection for asthma available on the NHS, called mepolizumab, which targets and blocks Interleukin-5. It then reduces the number of eosinophils in the body, leading to a reduction in asthma exacerbations.
Once mepolizumab has been initiated for severe asthma, the additional role of oral corticosteroids is questionable, as their main target is reduction of eosinophils. With mepolizumab treatment, blood eosinophils are significantly suppressed but not exhaled nitric oxide, a marker of eosinophilic inflammation. Both these markers are associated with a similar inflammatory phenotype of asthma, but the local Type 2 cytokine driven mechanism response may be independent of the IL-5 driven blood eosinophil response and elevated FeNO may indicate on-going T2 inflammation that is not affected by IL-5 suppression. There could be other features of asthma that remain untreated related to airway smooth muscle irritability and mast cells, rendering an IL-5 blocker an important, but partial treatment for severe asthma.
In this study, we will include 24 patients who are due to receive mepolizumab injections on the NHS. After a baseline assessment of inflammatory markers, we will review them after 12 weeks of mepolizumab treatment and record the inflammatory biomarkers again. We will then randomise them to a crossover study where they will receive 14 days of prednisolone and 14 days of placebo with a 4 week washout period in between. This is to understand the inflammation that persists after IL-5 is blocked and the further response of the T2 pathway to high dose corticosteroids. The inflammation following the steroids will be compared to placebo to understand any potential benefit of oral steroids to asthma inflammation, once established on Mepolizumab therapy.
REC name
West of Scotland REC 3
REC reference
18/WS/0060
Date of REC Opinion
29 Mar 2018
REC opinion
Favourable Opinion