Adrenal function recovery after durable oral corticosteroid sparing with benralizumab in the PONENTE study.

BACKGROUND

Oral corticosteroid (OCS) dependence among patients with severe eosinophilic asthma can cause adverse outcomes, including adrenal insufficiency. PONENTE's OCS reduction phase showed that, following benralizumab initiation, 91.5% of patients eliminated corticosteroids or achieved a final dosage ≤5 mg·day

METHODS

The maintenance phase assessed the durability of corticosteroid reduction and further adrenal function recovery. For ∼6 months, patients continued benralizumab 30 mg every 8 weeks without corticosteroids or with the final dosage achieved during the reduction phase. Investigators could prescribe corticosteroids for asthma exacerbations or increase daily dosages for asthma control deteriorations. Outcomes included changes in daily OCS dosage, Asthma Control Questionnaire (ACQ)-6 and St George's Respiratory Questionnaire (SGRQ), as well as adrenal status, asthma exacerbations and adverse events.

RESULTS

598 patients entered PONENTE; 563 (94.1%) completed the reduction phase and entered the maintenance phase. From the end of reduction to the end of maintenance, the median (range) OCS dosage was unchanged (0.0 (0.0-40.0) mg), 3.2% (n=18/563) of patients experienced daily dosage increases, the mean ACQ-6 score decreased from 1.26 to 1.18 and 84.5% (n=476/563) of patients were exacerbation free. The mean SGRQ improvement (-19.65 points) from baseline to the end of maintenance indicated substantial quality-of-life improvements. Of patients entering the maintenance phase with adrenal insufficiency, 32.4% (n=104/321) demonstrated an improvement in adrenal function. Adverse events were consistent with previous reports.

CONCLUSIONS

Most patients successfully maintained maximal OCS reduction while achieving improved asthma control with few exacerbations and maintaining or recovering adrenal function.

Informations de copyright

Copyright ©The authors 2022.

Déclaration de conflit d'intérêts

Conflict of interest: A. Menzies-Gow has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Sanofi and Teva, and is a steering committee member for the AstraZeneca PONENTE study; received speakers’ fees from AstraZeneca, Novartis, Sanofi and Teva; participated in research with AstraZeneca, for which his institution has been remunerated; attended international conferences with Teva; and made consultancy agreements with AstraZeneca and Sanofi. M. Gurnell is a steering committee member for the AstraZeneca PONENTE study; received travel support from AstraZeneca; and has received speakers’ fees from AstraZeneca, Novartis and Teva. L.G. Heaney is academic lead for the UK MRC Consortium for Stratified Medicine in Severe Asthma; he is industrial partner with Amgen, AstraZeneca, MedImmune, Janssen, Novartis, Roche/Genentech, GlaxoSmithKline and Boehringer Ingelheim; has prior project grant funding from MedImmune, Novartis UK, Roche/Genentech and GlaxoSmithKline; has taken part in advisory boards/lectures supported by AstraZeneca, Chiesi, Novartis, Roche/Genentech, GlaxoSmithKline, Teva, Theravance and Vectura; received travel funding support to attend international respiratory meetings from AstraZeneca, Chiesi, Novartis, Boehringer Ingelheim, Teva and GlaxoSmithKline; and has taken part in asthma clinical trials for GlaxoSmithKline, Schering-Plough, Synairgen, Novartis and Roche/Genentech, for which his institution was remunerated. J. Corren has received grants from AstraZeneca, in addition to grants and personal fees from Genentech, Novartis, Regeneron Pharmaceuticals and Sanofi. E.H. Bel reports grants from GlaxoSmithKline and Teva, which were paid to her institution; serves on the AstraZeneca data safety monitoring board for benralizumab; is a steering committee member for the AstraZeneca PONENTE and NOVELTY studies; serves on the GlaxoSmithKline Nucala Global Steering Committee; and received personal fees from GlaxoSmithKline, AstraZeneca, Chiesi, Sanofi/Regeneron and Teva. J. Maspero has consulted for AstraZeneca, Sanofi and Teva; was a speaker for GlaxoSmithKline, Menarini, Novartis and Uriach; and received research grants from Novartis. T. Harrison reports grants from AstraZeneca and the National Institute for Health Research, UK; personal fees and non-financial support from AstraZeneca; and is a steering committee member for the AstraZeneca PONENTE study, GlaxoSmithKline, Vectura, Boehringer Ingelheim, Chiesi and Synairgen; during the study's completion, he also became an employee of AstraZeneca. D.J. Jackson has received speakers’ honoraria from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Teva, and honoraria for attending advisory panels with AstraZeneca, GlaxoSmithKline, Novartis, Chiesi, Sanofi/Regeneron and Teva. D. Price has advisory board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme and Thermo Fisher; consultancy agreements with Airway Vista Secretariat, AstraZeneca, Boehringer Ingelheim, Chiesi, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, GlaxoSmithKline, Mylan, Mundipharma, Novartis, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc., Strategic North Limited, Synapse Research Management Partners SL, Talos Health Solutions, Theravance and WebMD Global LLC; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Theravance and UK National Health Service; received payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals and Sanofi Genzyme; received payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis and Thermo Fisher; has stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); has 5% shareholding in Timestamp, which develops adherence monitoring technology; is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. N. Lugogo received consulting fees for advisory board participation from Amgen, AstraZeneca, Genentech, GlaxoSmithKline, Novartis, Regeneron, Sanofi and Teva; honoraria for non-speakers’ bureau presentations from GlaxoSmithKline and AstraZeneca; and travel support from AstraZeneca; her institution received research support from Amgen, AstraZeneca, Avillion, Evidera, Gossamer Bio, Genentech, GlaxoSmithKline, Regeneron, Sanofi, Novartis and Teva. J. Kreindler, A. de Giorgio-Miller, S. Faison and K. Padilla are full-time employees of and stockholders in AstraZeneca. K. Padilla is also a member of the board of advisors for TruLab, Inc., Durham, NC. U.J. Martin was an employee of and stockholder in AstraZeneca at the time of the study. A. Burden was a contract employee of AstraZeneca at the time of the study; her current affiliation is Ardnamhor Consulting Limited, Kilcreggan, UK. E. Garcia Gil was an employee and stockholder of AstraZeneca at the time of the study; her current affiliation is Almirall, Barcelona, Spain.