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. 2019 Sep 25;5(3):00009-2019.
doi: 10.1183/23120541.00009-2019. eCollection 2019 Jul.

Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial

Andrew Menzies-Gow  1 , Jonathan Corren  2   3 , Elisabeth H Bel  4 , Jorge Maspero  5 , Liam G Heaney  6 , Mark Gurnell  7 , Peter Wessman  8 , Ubaldo J Martin  9 , Shahid Siddiqui  9 , Esther Garcia Gil  10
Affiliations

Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial

Andrew Menzies-Gow et al. ERJ Open Res. .

Abstract

Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody approved in several countries for the add-on maintenance treatment of patients with severe eosinophilic asthma aged 12 years and older. In the 28-week Phase III ZONDA trial (ClinicalTrials.gov identifier: NCT02075255), benralizumab produced a median 75% reduction from baseline in oral corticosteroid (OCS) dosage (versus 25% for placebo) while maintaining asthma control for patients with OCS-dependent severe asthma. This manuscript presents the detailed protocol for the Phase IIIb PONENTE (ClinicalTrials.gov identifier: NCT03557307), a study that will build on the findings from ZONDA. As the largest steroid-sparing study undertaken in severe asthma, PONENTE has a faster steroid tapering schedule for prednisone dosages ≥7.5 mg·day-1 than previous studies, and it includes an evaluation of adrenal insufficiency and an algorithm to taper OCS dosage when prednisone dosage is ≤5 mg·day-1. It also has a longer maintenance phase to assess asthma control for up to 6 months after completion of OCS tapering. The two primary endpoints are whether patients achieve 100% reduction in daily OCS use and whether patients achieve 100% reduction in daily OCS or achieve OCS dosage ≤5 mg·day-1, if adrenal insufficiency prevented further reduction, both sustained over ≥4 weeks without worsening of asthma. Safety and change from baseline in health-related quality of life will also be assessed. PONENTE should provide valuable guidance for clinicians on tapering OCS dosage, including the management of adrenal insufficiency, following benralizumab initiation for the treatment of patients who are OCS-dependent with severe, uncontrolled eosinophilic asthma.

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Conflict of interest statement

Conflict of interest: A. Menzies-Gow reports consultancy agreements with and advisory board membership for AstraZeneca, consultancy agreements with Sanofi and Vectura, advisory board membership for Boehringer Ingelheim, GlaxoSmithKline, Novartis, Sanofi and Teva, receiving speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis, Teva and Vectura, clinical funding from AstraZeneca, having participated in research for which his institution was renumerated by AstraZeneca, and having attended international conferences with sponsorship from Teva and Boehringer Ingelheim, outside the submitted work. Conflict of interest: J. Corren has nothing to disclose. Conflict of interest: E.H. Bel reports grants for research and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Sanofi-Regeneron, Sterna, Teva, and Vectura. Conflict of interest: J. Maspero reports consultancy for Sanofi, Teva, Novartis and GlaxoSmithKline, speaker fees from Boehringer Ingelheim, AstraZeneca, Menarini, Novartis and Uriach, and research and grants from Sanofi, AstraZeneca and Novartis, outside the submitted work. Conflict of interest: L.G. Heaney has nothing to disclose. Conflict of interest: M. Gurnell has nothing to disclose. Conflict of interest: P. Wessman is an employee of AstraZeneca. Conflict of interest: U.J. Martin is an employee of AstraZeneca. Conflict of interest: S. Siddiqui is an employee of AstraZeneca. Conflict of interest: E. Garcia Gil is an employee of AstraZeneca.

Figures

FIGURE 1
FIGURE 1
PONENTE study design. EOT: end of treatment; OCS: oral corticosteroid; Q4W: every 4 weeks; Q8W: every 8 weeks. #: guided by schema of OCS reduction defined in the study protocol.
FIGURE 2
FIGURE 2
OCS down-titration schema until dosage of 5 mg·day−1 is reached, without worsening of asthma. OCS: oral corticosteroid; Q1W: every week; Q2W: every 2 weeks; Q4W: every 4 weeks.
FIGURE 3
FIGURE 3
Hypothalamic–pituitary–adrenal axis evaluation and oral corticosteroid down-titration schema from prednisone dosage of 5 mg·day−1. ACTH: adrenocorticotropic hormone; AI: adrenal insufficiency; i.v.: intravenous; Q4W: every 4 weeks.
FIGURE 4
FIGURE 4
Rescue down-titration after recovery from asthma exacerbation or deterioration. OCS: oral corticosteroid; Q4W: every 4 weeks.
See this image and copyright information in PMC

References

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