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 effects 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. In addition, reports of oral corticosteroid to ICS dose-equivalence in terms of adrenal suppression were 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 11 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.
Abstract
In oral corticosteroid-dependent asthma, the majority of the oral corticosteroid-sparing effects of high-dose inhaled corticosteroids (ICS) are due to their systemic effects. Clinicians should be aware of this bioequivalence when prescribing high-dose ICS. http://bit.ly/2m0Fa8m
Footnotes
This review and meta-analysis is registered with PROSPERO (registration number: CRD42019119674).
Conflict of interest: I. Maijers has nothing to disclose.
Conflict of interest: N. Kearns has nothing to disclose.
Conflict of interest: J. Harper has nothing to disclose.
Conflict of interest: M. Weatherall has nothing to disclose.
Conflict of interest: R. Beasley reports grants from Health Research Council of New Zealand, during the conduct of the study; grants and personal fees for lectures and advisory board work, and travel expenses to attend meetings from AstraZeneca, grants from GlaxoSmithKline and Genentech, personal fees for advisory board work and travel expenses to attend meetings from Theravance Biopharma, outside the submitted work.
Support statement: The MRINZ is supported by Independent Research Organisation funding by the Health Research Council of New Zealand. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received June 12, 2019.
- Accepted September 16, 2019.
- Copyright ©ERS 2020