Background
No consensus exists on the right way to scale back oral corticosteroids after the initiation of
biologics in extreme bronchial asthma. The PONENTE trial evaluated the effectiveness and security
of a speedy, individualised steroid-reduction algorithm, together with adrenal insufficiency
monitoring, after benralizumab initiation.
Strategies
centres throughout 17 international locations. We enrolled grownup sufferers (age ≥18 years) with extreme,
eosinophilic bronchial asthma (blood eosinophil depend ≥150 cells per μL at enrolment or ≥300
cells per μL within the earlier yr) requiring upkeep oral corticosteroids for
at the least 3 months previous enrolment. Sufferers obtained benralizumab 30 mg (subcutaneous
injection) each 4 weeks for 3 doses, then each 8 weeks thereafter. The oral
corticosteroid discount section started at week 4 with every day oral corticosteroid dosages
diminished by 1–5 mg each 1–4 weeks relying on the beginning dosage, bronchial asthma management,
and adrenal operate standing. Adrenal operate was assessed with an early morning serum
cortisol measurement, adopted by adrenocorticotropic hormone stimulation when required,
as soon as sufferers achieved a every day oral corticosteroid dosage of 5 mg/day for 4 weeks.
Repeat cortisol measurements had been taken for sufferers with proof of adrenal insufficiency
at first testing. Bronchial asthma management was assessed with the Bronchial asthma Management Questionnaire-6
(ACQ-6) weekly all through the induction and oral corticosteroid discount phases.
The first endpoints had been the share of sufferers eliminating every day oral corticosteroids,
sustained for at the least 4 weeks, and the share attaining elimination or a every day
prednisone or prednisolone dosage of 5 mg or much less, for at the least 4 weeks, if the explanation
for no additional discount was adrenal insufficiency. Security and efficacy analyses included
all sufferers who obtained at the least one dose of benralizumab and had been descriptive.
We current outcomes after the oral corticosteroid discount section; a upkeep section
is ongoing. The trial is registered with ClinicalTrials.gov, NCT03557307.
Findings
Between April 1, 2018, and Sept 5, 2020, of 705 sufferers assessed for eligibility,
598 had been recruited and all obtained at the least one dose of benralizumab. Total, 376
(62·88%, 95% CI 58·86–66·76) of 598 sufferers eradicated oral corticosteroids and 490
(81·94%, 78·62–84·94) of 598 eradicated use or achieved a dosage of 5 mg or much less if
the explanation for stopping the discount was adrenal insufficiency. Subgroup evaluation
confirmed that dosage reductions had been achieved no matter baseline eosinophil depend,
baseline oral corticosteroid dosage, or oral corticosteroid remedy length. Adrenal
insufficiency was detected in 321 (60%) of 533 sufferers at first evaluation and in
205 (38%) of 533 sufferers 2–3 months later. The security profile was per
earlier expertise. Most sufferers (448 [75%] of 598) had no bronchial asthma exacerbations
throughout the oral corticosteroid discount section with an annualised exacerbation fee
of 0·63. Of 598 sufferers, 38 (6%) skilled a complete of 46 exacerbations ensuing
in emergency division or pressing care visits or hospitalisations.
Interpretation
Regardless of a excessive prevalence of adrenal insufficiency, most sufferers with eosinophilic
bronchial asthma handled with benralizumab achieved elimination of oral corticosteroids or maximal
attainable discount utilizing a personalised dosage-reduction algorithm.
Funding
AstraZeneca.
