Biologic Eliminates or Reduces Oral Steroids in Severe Asthma: PONENTE Trial

The majority of oral corticosteroid (OCS)-dependent patients with severe asthma taking benralizumab were able to discontinue OCS therapy completely or achieve maximal dose reduction, according to research to be presented 2021 American Academy of Allergy, Asthma and Immunology (AAAAI) Virtual Annual Meeting, Friday, February 26 – Monday, March 1, 2021.

The phase 3b PONENTE trial demonstrated that that benralizumab could eliminate or reduce OCS to physiologic dosages across a range of eosinophil levels.

The multicenter, open label, single-arm study included 598 patients and evaluated the safety and efficacy of daily reductions of OCS after initiation of benralizumab 30 mg. Enrolled adult patients had severe eosinophilic asthma requiring high-dose inhaled corticosteroids (ICS) plus long-acting beta2-agonist (LABA) and long-term use of OCS therapy with or without additional asthma controller(s). Patients recruited into the study had been on a maintenance OCS dose of ≥5 mg of prednisone for at least 3 months and had a baseline peripheral blood eosinophil count of ≥150 cells/μL or baseline eosinophils <150 cells/μL with a documented eosinophil count of ≥300 cells/μL in the past 12 months.

After a 4-week induction period with no OCS adjustments, patients began rapid down-titration following an OCS dosage-reduction algorithm, including individualized reductions if adrenal insufficiency (AI) was suspected. A 24-32-week maintenance phase followed.

Primary outcome measures were the proportion of patients achieving a 100% reduction in daily OCS dose and the proportion of patients achieving a 100% reduction or a daily OCS dose of ≤5 mg if the reason for no further OCS reduction was adrenal insufficiency, both sustained for at least 4 weeks without worsening of asthma.

OCS use was eliminated in most patients (62.2% [95% CI 58.18-66.11]); 80.6% (95% CI 77.20-83.70) eliminated use or reduced the daily dosage to ≤5 mg if AI prevented further reduction.

Median OCS daily dosage was reduced by 100%, and 91.3% of patients achieved a daily OCS dosage ≤5 mg. OCS reductions were achieved across baseline eosinophil counts. A lower percentage of patients had exacerbations during the OCS reduction phase than in the previous 12 months (25.8% vs 84.4%). Initially, 60% of patients had partial (33%) or complete (27%) AI, which decreased to 38.5% (18.1% and 19.4%, respectively) over the next 2-3 months.

The OCS reductions achieved using the individualized corticosteroid tapering algorithm are particularly important, according to Professor Andrew Menzies-Gow, director of the Lung Division, Royal Brompton Hospital, London, UK, the principal investigator of the PONENTE trial, “…because adrenal insufficiency can be a barrier to safe and meaningful oral corticosteroid reduction. These data should inform severe asthma treatment guidelines and strengthen physicians’ confidence to more safely eliminate chronic oral corticosteroid use in their patients” said Menzies-Gow in a press release from benralizumab manufacturer AstraZeneca

The abstract (#L48) will be presented at the 2021 AAAAI Virtual Annual Meeting.

The full meeting program is available on the AAAAI website.