The PONENTE study is likely to shape future clinical practice for oral corticosteroid (OCS) tapering following the initiation of benralizumab for OCS-dependent individuals with eosinophilic asthma, according to findings recently published in ERJ Open Research. The results will include techniques for managing adrenal insufficiency.
The PONENTE study (ClinicalTrials.gov Identifier: NCT03557307) is an ongoing phase 3b, open-label, multicenter trial that builds on the 28-week ZONDA trial (ClinicalTrials.gov Identifier: NCT02075255), which demonstrated benralizumab’s efficacy in reducing OCS dosage without decreasing asthma control. In PONENTE, researchers will aim to enroll 600 men and women from 180 clinical centers worldwide. The study began on August 1, 2018, and will run to approximately October 2020. Participants will all receive or switch to prednisone/prednisolone and will undergo a 4-week induction phase, a faster tapering phase than in previous studies, and 24 to 32 weeks of maintenance. Although OCS dosage will not be adjusted in the induction phase, it will be adjusted as needed in the maintenance phase. Asthma Control Questionnaire 6 scores will be collected every week.
There are 2 primary end points of the PONENTE study. The first is a 100% reduction in daily dosage of OCS, with at least 1 month of maintenance without asthma exacerbations. The other end point is whether participants reach 100% daily OCS reduction or a dosage of ≤5 mg/d, and if OCS reduction is precluded by adrenal insufficiency, this end point includes maintenance for at least 1 month without asthma exacerbations.
Safety outcomes will include the annual severe asthma exacerbation rate, adverse and severe adverse events, vital signs, laboratory variables, glucocorticoid toxicity index, annual rate of acute exacerbations resulting in emergency department visits or hospitalization, and incidence of total adrenal insufficiency.
Limitations to this study include a phase for OCS adjustment, as well as the lack of a control group.
The researchers concluded that the PONENTE trial “will provide valuable guidance for clinicians on tapering OCS dosage … following benralizumab initiation for the treatment of OCS-dependent patients with severe, uncontrolled eosinophilic asthma.” The study researchers aim to guide clinical procedures for tapering of OCS after initiation of biologics in the future.
Disclosure: This clinical trial was supported by AstraZeneca. Please see the original reference for a full list of authors’ disclosures.
Menzies-Gow A, Corren J, Bel EH, et al. Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial. ERJ Open Res. 2019;5(3). pii:00009-2019.