Hypereosinophilia is found in many exacerbations of asthma and COPD. It is present in almost half of asthma exacerbations and a third of COPD exacerbations. But we do not know whether the administration of anti-IL5 — in the form of a single injection of beralizumab — is beneficial in the acute stage of this type of exacerbation. This is what a double-blind randomized phase 2 study recently published in the Lancet tested with encouraging results (1). In the arms having received this anti-IL5 alone, or combined with corticosteroids, treatment failures of the exacerbation are in fact significantly less frequent at three months and the symptoms less significant at one month.
A randomized, double-blind, three-arm phase 2 study
The Abra study (for acute exacerbations treated with benralizumab) is a multicenter, double-blind, three-arm phase 2 study with two placebos in two UK hospitals. It was sponsored by the University of Oxford.
Adult subjects were recruited from the emergency room when they presented with an exacerbation of asthma or COPD associated with an eosinophil level greater than or equal to 300 cells/μl. These previously known subjects must have already been diagnosed with asthma or COPD, have had an exacerbation within the year and have a history of hypereosinophilia (more than 250 cells/μl).
They were randomized after stratification on their pathology (asthma or COPD), their FEV1 (less than 50%, at least 50%), their smoking (non-smoker, ex-smoker, smoker) and the number of annual exacerbations. (less than two, at least two/year) in three arms (1/1/1):
— A “Benra-Pred” arm combining an injection of beralizumab (100 mg SC) and corticosteroids (prednisolone at 30 mg/day, 5 days)
— A “Benra” arm treated with the sole injection of beralizumab
— A “Pred” arm, treated with corticosteroids alone.
A total of 158 patients were included between May 2021 and February 2024.
Their average age is 57 and 54% are women.
Among them, more than half suffered from asthma (56%), a third from COPD (32%) and just over one in ten had both asthma and COPD (12%).
The primary endpoint includes the rate of treatment failure at three months (death, rehospitalization or need for retreatment with corticosteroids or antibiotics) and symptomatology (VAS score of cough, dyspnea, wheezing, purulent sputum, sputum production and overall exacerbation ) at one month, in the two arms having received anti-IL5 (Benra and Benra-Pred), versus the corticosteroid-only control arm (Pred).
Fewer failures at three months and better symptoms at one month
At 3 months, there was 74% failure in the corticosteroid arm (Pred arm), 47% failure in the Benra arm and 42% failure in the Benra-Pred arm. Result, we observe a significant difference in the failure rates, between the corticosteroids alone arm, and the two arms having received the anti-IL5, analyzed together. (74 vs 45%; RR = 0.26 [0,13-0,56] ; p = 0,0005).
Already, at one month, the failures are significantly fewer. There are 45% failures in the corticosteroid arm versus 25% in the Benra arm and 19% in the Benra-Pred arm. That is, a significant difference between the corticosteroid arm and the Benra arms taken together (RR = 0.30), but no difference between the two arms having received the anti-IL5.
At the same time, the symptomatology at one month is even better in the arms having received anti-IL5 as a whole, than in the corticosteroid arm (mean difference: 49 [14-84] mm on a scale of 0 to 100; p = 0.0065). When we examine each arm separately, we also highlight a significant difference in favor of the Benra arm over the corticosteroid arm and the Benra-Pred arm over the corticosteroid arm.
Finally, the time to failure is significantly longer in the Benra arms taken as a whole than in the corticosteroid arm (RR = 0.39 [0,25-0,61]). However, there is no difference between the Benra alone and Benra-Pred arms.
For the authors, this work highlights that “the administration of anti-IL5 in the acute phase, associated or not with corticosteroids, is very interesting in patients presenting an exacerbation of asthma or COPD associated with hypereosinophilia”. According to the editorialist who commented on this work, “this opens a new era in the way of considering, treating and managing these exacerbations” (2).
(1) Sanjay Ramakrishnan et al. Treating eosinophilic exacerbations of asthma and COPD with benralizumab (ABRA): a double-blind, double-dummy, active placebo-controlled randomised trial. Lancet Respir Med 2024
(2) C Leung et al. A new era in the treatment of acute exacerbations of asthma and COPD. Lancet Respir Med 2024
