Benralizumab may help reduce OCS reliance in asthma
Patients with asthma reliant on oral corticosteroids (OCS) may be able to gradually cease or reduce their OCS dose after initiating treatment with benralizumab, according to results of the phase IIIb PONENTE* trial.
This multicentre, open-label, single-arm study comprised 598 adults (mean age 53.3 years, 64 percent female, 80.6 percent White) with asthma requiring high-dose inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) for ≥6 months plus OCS (≥5 mg prednisone or equivalent) for ≥3 months, and with blood eosinophil counts ≥150 cells/μL at baseline or ≥300 cells/μL in the past 12 months.
Median OCS dose at baseline was 10 mg/day, with 24.9 percent of patients exceeding this dose and 42.8 percent on a >5 to ≤10 mg/day dose. About 84 percent of patients had experienced an asthma exacerbation (median two exacerbations) in the previous year.
Following enrolment, patients received subcutaneous benralizumab during the induction (4 weeks of stable OCS) and OCS reduction (beginning at week 4 after second benralizumab dose using a dose-reduction algorithm) phases at a dose of 30 mg Q4W for the first three doses, then Q8W until end of treatment. Personalized reductions were possible if patients had adrenal insufficiency. The reductions were halted if patients experienced two exacerbations or there was indication of adrenal insufficiency on two tests 2 months apart (complete insufficiency on both tests or partial insufficiency on the first test and complete insufficiency on the second).
Almost two-thirds of patients (62.2 percent) eliminated their OCS use (reduction sustained for ≥4 weeks without worsening of asthma), while 80.6 percent either eliminated OCS use or reduced their daily dose to ≤5 mg if further reduction was not possible due to adrenal insufficiency. [AAAAI 2021, abstract L45]
Median daily dose of OCS was reduced by 100 percent, with 91.3 percent of patients reducing their daily dose to ≤5 mg.
These reductions or eliminations occurred regardless of baseline eosinophil levels. For instance, 60.2, 67.1, and 58.1 percent of patients with baseline eosinophil counts of <150, ≥150 to <300, and ≥300 cells/μL, respectively, achieved 100 percent reduction in OCS dose. Similarly, 75.6, 82.9, and 80.5 percent, respectively, achieved 100 percent reduction or OCS dose of ≤5 mg/day (if adrenal insufficiency prevented further OCS reduction), while 91.1, 91.9, and 91.0 percent, respectively, reduced their OCS dose to ≤5 mg/day.
Exacerbations, defined as worsening of asthma symptoms requiring temporary systemic corticosteroids, emergency department (ED) or urgent care visit, or asthma-related hospitalization, occurred in fewer patients during the OCS reduction period compared with the previous year (25.8 percent vs 84.4 percent). Thirty-nine patients (6.5 percent) experienced ≥1 exacerbation that required an ED or urgent care visit, or hospitalization (47 events in total).
Partial or complete adrenal insufficiency reduced over time, present in 60 percent of patients at baseline, and reducing to 37.5 percent 2–3 months later.
“There is currently a lack of evidence guiding OCS withdrawal following biologic initiation in severe asthma,” pointed out study author Professor Andrew Menzies-Gow from the Royal Brompton & Harefield NHS Foundation Trust, London, UK, at AAAAI 2021.
“In the ZONDA trial, benralizumab led to a 75 percent median reduction in OCS dosage at week 28 (compared with a 25 percent reduction with placebo) for patients with eosinophil levels ≥150 cells/μL,” he said. However, this trial was not designed to assess OCS reduction methods.
“[The PONENTE trial showed that] irrespective of baseline eosinophil count, most OCS-dependent asthma patients treated with benralizumab achieved OCS elimination or maximal possible reduction in those in whom adrenal insufficiency was detected,” he continued.
“[These findings] can inform physician decisions and clinical practice by supporting the use of a personalized OCS-reduction algorithm,” Menzies-Gow concluded.