adherence to inhaled corticosteroids in severe asthmatics on biologics
Research type
Research Study
Full title
The influence of inhaled CorticoSteroids Adherence on treatment Response to mepolizumab in severe Eosinophilic Asthma (CSAREA study)
IRAS ID
290858
Contact name
Adel Mansur
Contact email
Sponsor organisation
University Hospitals Birmingham
Duration of Study in the UK
2 years, 0 months, 30 days
Research summary
Research Summary:
Severe asthma afflicts about 5% of the overall asthma. Patients with severe asthma suffer from disabling disease with profound effect on the individual and the society including the high usage of health services. Traditionally high dose of systemic corticosteroids were used as the main stay treatment for severe asthma. However corticosteroids cause major sided effects and an alternative biological treatments have become available now in the treatment of severe asthma. These precision medicines proved to be effective in severe asthma with favourable side effects profile. Mepolizumab is an example of these biologic treatment that is now used in all severe asthma centres in the UK and globally. Response rate to mepolizumab is around 70% with smaller minority still do not derive benefit from this treatment. Factors that can predict which patient will respond to mepolizumab and which do not remained unknown. One possible factor is the non-adherence to controller treatment in the form of inhaled corticosteroids which is needed along side mepolizumab to control asthma. Non-adherence to inhaled corticosteroids in asthma has been associated with poor asthma control and exacerbations leading to emergency hospital visits and admissions.Lay summary of study results:
Adherence to a prescribed medication means that a patient takes such medication in a manner that is agreed upon with a healthcare provider (Hartge, 2015). Patients with the severe form of asthma usually express high level of asthma markers of inflammation such as blood eosinophils which are a type of white blood cells that tend to be active in asthma, and a gas termed “nitric oxide” which can be measured in the exhaled breath and its level tends to be high in asthma (fraction exhaled nitric oxide “FeNO). Patients with severe asthma require treatment with high-dose inhaled corticosteroid (ICS) to control their asthma symptoms and reduce risk of flare ups (asthma attacks) (Gibson & McDonald, 2017). However, for many patients, preventer treatment with inhalers alone is not adequate and treatment escalation is needed. Progress in asthma treatment made over last few years led to the development of biologic treatments (monoclonal antibodies) which target specific proteins in the blood “cytokines” and can control asthma in effective and safe way. Mepolizumab is one of these biological treatment used now in asthma treatment and has been shown to improve asthma (Reilly et al., 2023). It was noted that some patients do not respond to mepolizumab and one possible reason for that is the inadequate use of the preventer treatment of ICS (non-adherence) whilst on mepolizumab treatment (Blake, 2017; Caminati et al., 2020). In this study we evaluated the influence of ICS non-adherence on the response to mepolizumab treatment by reviewing records of asthma patients aged 18 years treated with mepolizumab from June 2017 to June 2023 in the Birmingham (UK) Regional Severe Asthma Service (BRSAS) network. We measured ICS adherence by counting the number of ICS prescriptions collected in the year before and the year on mepolizumab treatment, and calculated the prescription possession ratio (number of inhalers collected / 12: PPR) which is one of the agreed upon ways of measuring adherence to treatment. A PPR of ≥75% was used to indicate an adherence status. A positive response to mepolizumab was defined as a 50% reduction in asthma attacks or reduction in the use of regular (maintenance) oral corticosteroid dose (OCS) for asthma. A total of 190 participants were included in the analysis, and positive response to mepolizumab was achieved in 153 (80%). Patients with a positive mepolizumab response had fewer asthma attacks per year than the negative responders (1 vs 4, respectively). In the non-responder group, ICS non-adherence was significantly more prevalent 12/23 (52%) than in the positive responder group 29/130 (22%). These results therefore showed an associated between non-adherence to ICS and negative response to mepolizumab. In addition, during mepolizumab treatment, FeNO level (a marker of airway inflammation and poor asthma control) was significantly higher in the non-adherent group than in the adherent patients [57 parts per billion (PPB) vs 34]. High FeNO level during mepolizumab treatment could therefore be a marker of ICS non-adherence. The study also found that those who were non-adherent before starting mepolizumab were more likely to remain non-adherent during mepolizumab treatment.
In conclusion, 80% of patients achieved positive response to mepolizumab demonstrating this treatment effectiveness in keeping with previous reports. This study confirmed its primary hypothesis that inadequate treatment with inhaled corticosteroids during mepolizumab treatment can result in a negative response. It also confirmed its secondary hypotheses that FeNO could be a marker of ICS non-adherence during mepolizumab treatment, and those who were non-adherent before starting mepolizumab are more likely to remain non-adherent during the treatment. This study findings support the notions, 1. to optimise ICS adherence during mepolizumab treatment to improve the chances of positive treatment response, 2. to use high FeNO as a possible marker of ICS non-adherence, and 3. To monitor ICS adherence more closely in patients who were found to be non-adherent prior to starting mepolizumab treatment. Applying effective strategies that promote ICS adherence during mepolizumab treatment is therefore now warranted to improve asthma control and mepolizumab treatment response rate.REC name
London - West London & GTAC Research Ethics Committee
REC reference
21/PR/1417
Date of REC Opinion
5 Nov 2021
REC opinion
Favourable Opinion