A subpopulation of patients with asthma treated with maximal inhaled treatments is unable to maintain asthma control and requires additional therapy with oral corticosteroids (OCS); a subset of this population continues to have frequent exacerbations. Alternate treatment options are needed as daily use of OCS is associated with significant systemic adverse effects that affect many body systems and have a direct association with the dose and duration of OCS use. We compared the population demographics, medical conditions and efficacy responses of the OCS-dependent group from the DREAM study of mepolizumab with the group not managed with daily OCS.
Trial Registration Number NCT01000506.
- Eosinophil Biology
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Mepolizumab, an anti-interleukin 5 monoclonal antibody under development for severe asthma, has been shown to reduce peripheral and sputum eosinophils.1 ,2 Mepolizumab is hypothesised to work by reducing eosinophilic driven airway inflammation. Mepolizumab has previously been shown to be steroid sparing in a small study.1 The DREAM study (NCT01000506) reported that mepolizumab can reduce the exacerbation rate by 39–52% in a severe asthma population.2 Approximately a third of the subjects (n=188) who participated in the DREAM study were using daily oral corticosteroids (OCS) at baseline in addition to using high dose inhaled corticosteroid and an additional controller to treat their asthma. This group reported an average duration of OCS use of 4.1 years, a mean OCS dose of 17 mg/day and a median peripheral blood baseline eosinophil level of 280 cells/µL, which was similar to that for the non-OCS dependent subgroup (290 cells/µL) (table 1). Sputum eosinophils levels were also similar between the OCS-dependent and non-OCS dependent groups, although only measured in a subset of subjects. Consistent with a recent finding from Severe Asthma Research Program (SARP), the OCS group also had greater baseline airway inflammation, as assessed by median FENO (table 1).3
Mean baseline ACQ scores indicated both subgroups were not controlled; the OCS-group had a mean ACQ-6 score of 2.5 compared with 2.3 (p=0.077) for the non-OCS group (table 2). Despite being on maximal therapy, the OCS group had a lower baseline mean FEV1, and lower FVC, and FEV1/FVC ratio when compared with the non-OCS group (table 1). The majority of subjects (75%) in the OCS group reported having three or more exacerbations in the year prior to the study compared with 44% of the non-OCS group; 49% of the OCS group had severe exacerbations that required asthma-related hospitalisation(s), intubation, or were considered near-fatal asthma events (table 3).
Mepolizumab reduced the peripheral eosinophils within 4 weeks of treatment and the effect was maintained for the duration of the study and was effective at reducing the frequency of exacerbations in the non-OCS and OCS groups during the 52-week treatment period with a numerically greater reduction noted in the OCS group (table 2).2 This difference was not statistically different. Placebo treated subjects in the OCS group had the highest exacerbation rate during the study. These results demonstrate that despite daily OCS use the OCS group continues to have severe disease impairment with persistent eosinophils, airway inflammation, reduced lung function, and are also at high risk for future exacerbations. These clinical parameters were reflected by the poor control status and poor quality of life reported at baseline. The efficacy results demonstrate that mepolizumab treatment of a population using OCS daily was able to reduce peripheral eosinophils and exacerbation risk to a similar extent as a non-OCS dependent group.⇓
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Contributors CMP and HO contributed to the conception and design of the work and in the acquisition, analysis, or interpretation of data. BFH, SW, JAD and NB contributed to the analysis, or interpretation of data. All authors contributed towards drafting the research letter and revising it critically for important intellectual content and provided final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding This study was funded by GlaxoSmithKline.
Competing interests None.
Patient consent Obtained.
Ethics approval The data presented within was a global clinical trial and various independent Ethics committees and IRBs reviewed and approved prior to study initiation.
Provenance and peer review Not commissioned; internally peer reviewed.