Acute Exacerbations Treated With BenRAlizumab (The ABRA Study)
Status:
Recruiting
Trial end date:
2024-11-19
Target enrollment:
Participant gender:
Summary
Exacerbations of asthma and COPD are an important cause of hospital admission and the main
cause of annual winter bed shortages. Despite current guideline treatment with prednisolone,
40% of patients require further treatment, 15% are readmitted and, of those hospitalised, 10%
die within 3 months, all by definition treatment failures. The investigators have shown that
there are two dominant patterns of airway inflammation in patients presenting with an acute
episode: infection associated neutrophilic airway inflammation; and non-infection related
eosinophilic airway inflammation. These patterns cannot be distinguished reliably by clinical
categories (i.e. asthma or COPD) or a standard clinical assessment but are identified by the
peripheral blood eosinophil count. These findings raise important questions that targeted
treatment based on the blood eosinophil count would result in more efficient and effective
management. However, even in patients with the right pattern of airway inflammation the
beneficial effects of prednisolone have to be offset against a high potential for harm, with
an estimated the number needed to harm as 5 for every 10 patients treated.
Benralizumab is an interleukin-5 receptor-α monoclonal antibody, injected subcutaneously,
which rapidly reduces peripheral blood eosinophils for 90 days with a satisfactory safety
profile. Benralizumab treatment at stable state has been shown to increase
post-bronchodilator FEV1 and reduce the rates of severe exacerbations in patients with severe
eosinophilic asthma and improve lung function in patients with eosinophilic COPD.
Benralizumab is an attractive candidate for the acute treatment of eosinophilic
exacerbations, without the side-effects of prednisolone. The investigators propose to test
the hypothesis that, for participants who have a raised eosinophil count at exacerbation, a
single injection of Benralizumab alone or in combination with prednisolone will improve
clinical outcomes compared to prednisolone alone. The investigators will also study the
effect of prednisolone on symptoms, lung function and quality of life, in an exacerbation
when the eosinophil count is not raised.