Abstract
Background The proportion of the efficacy of high dose inhaled corticosteroids (ICS) in oral corticosteroid-dependent asthma that is due to systemic effects is uncertain. This study aimed to estimate the ICS dose-response relationship for oral corticosteroid sparing effects in oral corticosteroid-dependent asthma, and to determine the proportion of oral corticosteroid sparing effect due to their systemic effects, based on the comparative dose-response relationship of ICS versus oral corticosteroids on adrenal suppression.
Methods Systematic review and meta-analysis of randomised controlled trials reporting oral corticosteroid sparing effects of high dose ICS in oral corticosteroid-dependent asthma. Reports of oral corticosteroid to ICS dose-equivalence in terms of adrenal suppression were additionally retrieved. The primary outcome was the proportion of the oral corticosteroid sparing effect of ICS that could be attributed to systemic absorption, per 1000 µg increase of ICS, expressed as a ratio. This ratio estimates the oral corticosteroid sparing effect of ICS due to systemic effects.
Results Eleven studies including 1283 participants reporting oral corticosteroid sparing effects of ICS were identified. The prednisone dose decrease per 1000 µg increase in ICS varied from 2.1 mg to 4.9 mg, depending on the type of ICS. The ratio of the prednisone sparing effect due to the systemic effects per 1000 µg of fluticasone propionate was 1.02 (95% CI 0.68–2.08) and for budesonide was 0.93 (95% CI 0.63–1.89).
Conclusion In patients with oral corticosteroid-dependent asthma, the limited available evidence suggests that the majority of the oral corticosteroid sparing effect of high dose ICS is likely to be due to systemic effects.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Maijers reports a grant from the Health Research Council of New Zealand, during the conduct of the study.
Conflict of interest: Dr. Kearns reports a grant from Health Research Council of New Zealand, during the conduct of the study.
Conflict of interest: Dr. Harper reports a grant from the Health Research Council of New Zealand, during the conduct of the study.
Conflict of interest: Dr. Weatherall has nothing to disclose.
Conflict of interest: Dr. Beasley reports grants from Health Research Council of New Zealand, during the conduct of the study; grants and personal fees from AstraZeneca, grants from GlaxoSmithKline, grants from Genentech, personal fees from Theravance Biopharma, outside the submitted work.
- Received June 12, 2019.
- Accepted September 16, 2019.
- Copyright ©ERS 2019
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