Elimination of Oral Corticosteroids (OCS) with Benralizumab Treatment in OCS-Dependent Asthmatics Using a Rapid, Personalized Algorithm: The PONENTE Trial

Abstract

Rationale: There is a lack of evidence guiding OCS withdrawal following biologic initiation in severe asthma. We aimed to demonstrate that benralizumab could eliminate or reduce OCS to physiologic dosages following a personalized OCS down-titration while monitoring for adrenal insufficiency (AI). Methods: This single-arm study of 598 patients assessed the efficacy and safety of daily OCS dosage reduction after initiation of benralizumab 30 mg. Adults with asthma requiring high-dosage ICS and LABA for ≥6 months plus OCS (≥5 mg prednisone or equivalent) for ≥3 months and blood eosinophil counts ≥150/μL at baseline or ≥300/μL in the previous 12 months were enrolled. Four weeks after benralizumab initiation, patients began an OCS dosage-reduction algorithm with rapid down-titration, including personalized reductions if AI was present. Results: Most patients (62.2% [95% CI 58.18-66.11]) eliminated OCS use, and 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 irrespective of baseline eosinophil count. Additionally, a lower percentage of patients had exacerbations during the OCS reduction phase than in the previous year (25.8% vs. 84.4%). Initially, 60% of patients had partial or complete AI (33% and 27%, respectively), which decreased to 38.5% (18.1% and 19.4%, respectively) 2-3 months later. Conclusions: Irrespective of baseline eosinophil count, most OCS-dependent asthmatics treated with benralizumab achieved OCS elimination or maximal possible reduction when AI was detected.