Benralizumab offers sustained remission in severe eosinophilic asthma

Treatment with benralizumab (BRZ) results in sustained remission in patients with severe eosinophilic asthma (SEA), particularly those with comorbid chronic rhinosinusitis with nasal polyps (CRSwNP) and reversible airflow limitation, reports a study.

“Our global assessment was based on a four-component evaluation, including three important clinical outcomes (ie, prevention of asthma exacerbations, oral corticosteroid elimination, and better symptom control) to which we have added data on lung function improvement,” the researchers said.

“It is thus very likely that an affordable sustained remission on-treatment of SEA can be successfully induced by BRZ because of its efficacy in dampening type 2 eosinophilic inflammation of airways,” they added. [Respirology 2024;29:869-879]

Some 164 patients with SEA were enrolled in this real-life, multicentre, and retrospective study. Participants received add-on biologic treatment with BRZ for 24 months.

After 2 years, 69 participants (42.1 percent) achieved sustained remission on-treatment (exacerbation rate=0, oral corticosteroid dose=0, prebronchodilator FEV₁ ≥80 percent pred., ACT score ≥20). Thirty-three out of 82 patients with concomitant CRSwNP also showed constant improvement (SNOT-22 <30, NP recurrence = 0) during the same period.

Notably, sustained remission on-treatment were associated independently with CRSwNP (odds ratio, 2.32; p<0.05) and with postbronchodilator reversibility of airflow limitation (OR, 5.59; p<0.01).

Mechanism

“The above mentioned clinical and functional effects of benralizumab can be reasonably explained by the powerful anti-eosinophilic action of this biologic drug,” the researchers said. “Indeed, we detected a sharp and persistent fall of blood eosinophil count, which dropped from the baseline geometric mean of 625.5 cells/μL to 0.0 cells/μL across all the timepoints of our study.”

Furthermore, asthmatic patients with blood eosinophil count higher than 300‒400 cells/μL were at greater risk of disease exacerbations. [J Allergy Clin Immunol Pract 2014;2:741-750; Lancet Respir Med 2015;3:849-858]

“After initiating treatment with BRZ, and throughout the study period, we did not detect any patient having more than 100 eosinophils/μL of blood,” the researchers said. “Eosinophil depletion elicited by BRZ was also likely responsible for the relevant improvement of lung function observed during the overall 2-year duration of our real-world investigation.”

In earlier studies, elevated blood eosinophil counts correlated with airflow obstruction. [N Engl J Med 1990;323:1033-1039]

“In conjunction with eosinophil depletion induced by BRZ, we detected higher FEV₁ increases (350, 310, 450, and 430 mL at 6, 12, 18, and 24 months of treatment, respectively) than those reported by several [trials], whose authors measured maximal FEV₁ increments consisting of 125, 159, and 80 mL, respectively,” the researchers said. [Lancet 2016;388:2115-2127; Lancet 2016;388:2128-2141]

“However, our real-life results suggest that a sustained clinical remission on-treatment of severe asthma was achieved by a relevant percentage of patients treated with BRZ, regardless of their baseline blood eosinophil count, which was anyway higher than 300 cells/μL in all of them,” they noted.

BRZ is not yet approved for the treatment of nasal polyps, but some studies suggest its efficacy in such condition. [Lancet Respir Med 2021;9:260-274; J Allergy Clin Immunol Pract 2021;9:4371-4380.e4; Int J Immunopathol Pharmacol 2020;34:2058738420950851]