Pneumologie 2021; 75(S 01): S35-S36
DOI: 10.1055/s-0041-1723326
Latebreaking Abstracts 2021

Adrenal Insufficiency is Not a Barrier to OCS Elimination in the PONENTE Study

M Gurnell
1   Wellcome-Mrc Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK
,
M G Andrew
2   Royal Brompton & Harefield NHS Foundation Trust, London, UK
,
L G Heaney
3   Centre for Experimental Medicine, Queenʼs University Belfast, Belfast, UK
,
J Corren
4   David Geffen School of Medicine at Ucla and Allergy Medical Clinic Inc., Los Angeles, Ca, USA
,
E H Bel
5   Amsterdam Umc, University of Amsterdam, Amsterdam, The Netherlands
,
J Maspero
6   Fundación Cidea, Buenos Aires, Argentina
,
T Harrison
7   Nottingham Respiratory Nihr Brc, University of Nottingham, Uk; Biopharmaceuticals R&d Digital, AstraZeneca, Cambridge, UK
,
D J Jackson
8   Guyʼs Severe Asthma Center, Guyʼs & St. Thomasʼ NHS Trust, London, Uk; Asthma UK Centre, School of Immunology & Microbial Sciences, Kingʼs College London, London, UK
,
D Price
9   Observational and Pragmatic Research Institute, Singapore; Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom
,
N Lugogo
10   University of Michigan Medical Center, Ann Arbor, MI, USA
,
J Kreindler
11   Global Medical Respiratory, Biopharmaceuticals Medical, AstraZeneca, Wilmington, De; USA
,
A Burden
12   Biopharmaceuticals R&d, Late Respiratory & Immunology, Biometrics, AstraZeneca, Cambridge, UK
,
A de Giorgio Miller
13   Medical & Scientific Affairs, Biopharmaceuticals Medical, AstraZeneca, Luton, UK
,
K Padilla
14   Late Respiratory & Immunology, Biopharmaceuticals R&d, AstraZeneca, Durham, Nc, USA
,
U J Martin
15   Late Stage Development, Respiratory and Immunology Therapeutic Area, AstraZeneca, Gaithersburg, MD, USA
,
E G Garcia Gil
16   Global Medical Respiratory, Biopharmaceuticals Medical, AstraZeneca, Barcelona, Spain
› Author Affiliations

Sponsor AstraZeneca
› Further Information
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    Rationale: Oral corticosteroid (OCS) dependence is prevalent in severe asthma and causes adverse effects, including adrenal insufficiency (AI). Benralizumab may reduce or eliminate the need for long-term OCS for adults with severe asthma. AI may be perceived as a barrier to OCS reduction, and limited data are available to guide the extent to which OCS can be tapered in the presence of AI.

    Methods: An analysis of patients in the multicenter, open-label phase III b PONENTE trial was conducted to demonstrate benralizumabʼs ability to eliminate or reduce the daily OCS dosage according to adrenal function status. Hypothalamic-pituitary-adrenal (HPA) axis integrity was evaluated after patients reached a daily OCS dosage of 5 mg for 4 weeks. A morning cortisol level was obtained to determine if patients had normal adrenal function (> 350 nmol/L) or complete AI (< 100 nmol/L). Patients with indeterminate results (100 – 350 nmol/L) underwent an ACTH stimulation test and were classified as having normal cortisol levels (> 450 nmol/L), complete AI (< 250 nmol/L), or partial AI (250 – 450 nmol/L). Adrenal status determined whether the OCS down-titration was continued or suspended (due to complete AI), and was re-evaluated 2 – 3 months later to guide further reductions; patients with a finding of complete AI at the second test were not allowed any further dosage reductions. Endpoints included OCS elimination and achieving a daily OCS dosage ≤ 5 mg.

    Results: 530 of 598 eligible patients completed the initial HPA axis assessment. At first testing, 40% of patients had normal cortisol levels, 33% had partial AI, and 27% had complete AI. Overall, more than one-third of patients with initial complete or partial AI recovered their adrenal function 2 to 3 months later (36.2% from partial AI to normal levels and 31.9% from complete AI to partial AI or normal levels). More than 90% of patients with normal adrenal function or who improved from partial AI to normal levels and more than 60% of patients who improved from complete AI to partial AI or normal levels eliminated OCS use.

    Conclusions: Most patients with normal adrenal function eliminated OCS or achieved a daily OCS dosage ≤ 5 mg, and a substantial percentage of patients with initially impaired adrenal function were able to reduce or eliminate OCS with careful management.


     

    Publication History

    Article published online:
    30 April 2021

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