Figures
- 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
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
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
Rescue down-titration after recovery from asthma exacerbation or deterioration. OCS: oral corticosteroid; Q4W: every 4 weeks.
Tables
- TABLE 1
Comparison of PONENTE study features with published oral corticosteroid (OCS)-sparing studies of other biological treatments for severe asthma
Study name Study type Trial duration Patients Biologic OCS inclusion criteria OCS tapering Time frame Dosage reduction PONENTE (ongoing) Open-label, single-arm >36 weeks (variable personalised OCS tapering period) + 4 weeks follow-up Aim: ∼600 Benralizumab ≥5 mg·day−1 of prednisone (or equivalent) Dose-reduction phase: variable depending on baseline OCS dosage
Maintenance phase: ∼24–32 weeks
Follow-up: 4 weeks (Week 36)OCS dosages will be reduced by 5 mg either weekly or every 2 weeks or by 2.5 mg every 4 weeks depending on baseline OCS use/loss of asthma control until reaching ≤5 mg·day−1
Following 4 weeks at ≤5 mg·day−1, further OCS reduction depends on cortisol concentration and AI status (evaluated by HPA axis integrity) assessed by ACTH stimulation testingZONDA [18] RCT 28 weeks + 8 weeks follow-up 220 Benralizumab 7.5–40.0 mg·day−1 of prednisone (or equivalent) 5–35 mg·day−1 of prednisone (or equivalent) Dose-reduction phase: 20 weeks (Week 4–24)
Maintenance phase: 4 weeks
Follow-up: 8 weeks (Week 36)OCS dosage reduced by 2.5–5 mg·day−1 every 4 weeks (until reaching a dosage of 7.5 mg·day−1, then further reduced to 5 mg·day−1, 1.25 mg·day−1, and 0 mg·day−1; only patients with OCS dosage of ≤12.5 mg·day−1 at the end of the run-in phase were eligible for a 100% dose reduction) SIRIUS [28] RCT 24 weeks 135 Mepolizumab 5–35 mg·day−1 of prednisone (or equivalent) Run-in optimisation phase: 3–8 weeks
Dose-reduction phase: 16 weeks (Week 4–20)
Maintenance phase: 4 weeks (Week 24)Run-in OCS optimisation phase: OCS reduced weekly until asthma worsening
Dose-reduction phase: OCS dosage reduced by 1.25–10 mg·day−1 every 4 weeks (based on asthma control and symptoms of AI); reduction only allowed for patients with stable ACQ-5 scores and for whom the investigator deemed appropriateVENTURE [29] International RCT 24 weeks 210 Dupilumab 5–35 mg·day−1 of prednisone (or equivalent) Dose-reduction phase: 16 weeks (Week 4–20)
Maintenance phase: 4 weeks
Follow-up: 12 weeksOCS dosage reduced every 4 weeks (protocol-specified algorithm; reduction range 2.5–25 mg·day−1, depending on baseline OCS dosage); no dose adjustments allowed after Week 20 RCT: randomised controlled trial; AI: adrenal insufficiency; HPA: hypothalamic–pituitary–adrenal; ACTH: adrenocorticotropic hormone; ACQ-5: five-item Asthma Control Questionnaire-5.
Supplementary Material
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Supplementary material 00009-2019.supp
