Efficacy and safety of amphotericin B formulations: a network meta-analysis and a multicriteria decision analysis

Tonin, FS; Steimbach, LM; Borba, HH; Sanches, AC; Wiens, A; Pontarolo, R; Fernandez-Llimos, F

Efficacy and safety of amphotericin B formulations: a network meta-analysis and a multicriteria decision analysis

Tonin, FS Steimbach, LM Borba, HH Sanches, AC Wiens, A Pontarolo, R Fernandez-Llimos, F

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Publication Type:: Journal Article
Citation:: Journal of Pharmacy and Pharmacology, 2017, 69 (12), pp. 1672 - 1683
Issue Date:: 2017-12-01

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Field	Value	Language
dc.contributor.author	Tonin, FS	en_US
dc.contributor.author	Steimbach, LM	en_US
dc.contributor.author	Borba, HH	en_US
dc.contributor.author	Sanches, AC	en_US
dc.contributor.author	Wiens, A	en_US
dc.contributor.author	Pontarolo, R	en_US
dc.contributor.author	Fernandez-Llimos, F https://orcid.org/0000-0002-8529-9595	en_US
dc.date.available	2017-07-17	en_US
dc.date.issued	2017-12-01	en_US
dc.identifier.citation	Journal of Pharmacy and Pharmacology, 2017, 69 (12), pp. 1672 - 1683	en_US
dc.identifier.issn	0022-3573	en_US
dc.identifier.uri	http://hdl.handle.net/10453/124567
dc.description.abstract	© 2017 Royal Pharmaceutical Society Objectives: Despite its broad spectrum, conventional amphotericin B (AB) is associated with serious adverse events. Lipid-based formulations may offer safer options. We aimed to synthesize the evidence of efficacy and safety of AB formulations. Methods: We performed a systematic review and network meta-analysis (NMA) to compare all available formulations: conventional AB; lipid complex or ABLC; colloidal dispersion or ABCD; liposomal or LAB; AB in Intralipid. Randomized controlled trials were searched in four databases. Cure, fever, chills, nephrotoxicity, death and drug discontinuation were assessed. NMA was based on Bayesian methods accounting for direct and indirect comparisons. Probability ranks estimating the best formulation were built for each outcome. The relative benefit–risk of formulations was assessed with stochastic multicriteria acceptability analyses (SMAA). Key findings: We identified 25 trials (n = 2996). No significant differences among drugs were observed for cure or death. All lipid-based formulations were safer than conventional AB for nephrotoxicity. AB-Intralipid was more tolerable than conventional AB and caused less chills than ABCD. AB-Intralipid was the best therapy (>60%) regarding nephrotoxicity, fever, chills and discontinuation. The scenario from SMAA favoured AB-Intralipid (81% acceptability). Conventional AB was secondary to all lipid-based formulations. Conclusions: Amphotericin B-Intralipid was identified as safer, cost-saving treatment in comparison with other formulations.	en_US
dc.relation.ispartof	Journal of Pharmacy and Pharmacology	en_US
dc.relation.isbasedon	10.1111/jphp.12802	en_US
dc.subject.classification	Pharmacology & Pharmacy	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Amphotericin B	en_US
dc.subject.mesh	Lipids	en_US
dc.subject.mesh	Antifungal Agents	en_US
dc.subject.mesh	Bayes Theorem	en_US
dc.subject.mesh	Chemistry, Pharmaceutical	en_US
dc.subject.mesh	Decision Support Techniques	en_US
dc.subject.mesh	Randomized Controlled Trials as Topic	en_US
dc.subject.mesh	Invasive Fungal Infections	en_US
dc.title	Efficacy and safety of amphotericin B formulations: a network meta-analysis and a multicriteria decision analysis	en_US
dc.type	Journal Article
utslib.citation.volume	12	en_US
utslib.citation.volume	69	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	1116 Medical Physiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
utslib.copyright.status	closed_access
pubs.issue	12	en_US
pubs.publication-status	Published	en_US
pubs.volume	69	en_US

Abstract:

© 2017 Royal Pharmaceutical Society Objectives: Despite its broad spectrum, conventional amphotericin B (AB) is associated with serious adverse events. Lipid-based formulations may offer safer options. We aimed to synthesize the evidence of efficacy and safety of AB formulations. Methods: We performed a systematic review and network meta-analysis (NMA) to compare all available formulations: conventional AB; lipid complex or ABLC; colloidal dispersion or ABCD; liposomal or LAB; AB in Intralipid. Randomized controlled trials were searched in four databases. Cure, fever, chills, nephrotoxicity, death and drug discontinuation were assessed. NMA was based on Bayesian methods accounting for direct and indirect comparisons. Probability ranks estimating the best formulation were built for each outcome. The relative benefit–risk of formulations was assessed with stochastic multicriteria acceptability analyses (SMAA). Key findings: We identified 25 trials (n = 2996). No significant differences among drugs were observed for cure or death. All lipid-based formulations were safer than conventional AB for nephrotoxicity. AB-Intralipid was more tolerable than conventional AB and caused less chills than ABCD. AB-Intralipid was the best therapy (>60%) regarding nephrotoxicity, fever, chills and discontinuation. The scenario from SMAA favoured AB-Intralipid (81% acceptability). Conventional AB was secondary to all lipid-based formulations. Conclusions: Amphotericin B-Intralipid was identified as safer, cost-saving treatment in comparison with other formulations.

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http://hdl.handle.net/10453/124567