Treatment of uncomplicated vulvovaginal candidiasis: topical or oral drugs? Single-day or multiple-day therapy? A network meta-analysis of randomized trials

Abstract

Objective: To assess early (7-10 days) and late (24-35 days) clinical and mycological cure rates associated with single or multiple-day topical or oral treatment of uncomplicated vulvovaginal candidiasis.

Data sources: Cochrane Central Register of Studies Online (inception to 31 March 2024), MEDLINE, Ovid platform (1946-31 March 2024), Embase, (inception to 31 March 2024), Google Scholar (inception to 31 March 2024), US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and European Clinical Trials Register.

Study eligibility criteria: Fifty (N=7208 subjects) randomized studies comparing different topical or oral drugs with or without placebo were included in the analysis. Confidence in the results of network meta-analysis was evaluated by using an online tool that combines confidence assessments arising from direct comparisons with network meta-analysis estimates. The risk of bias of individual studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials.

Study appraisal and synthesis methods: Bayesian network meta-analysis was performed using an interactive web-based tool with the R packages gemct and BUGSNET. Ranking success probabilities were computed on the basis of the surface under the cumulative ranking curve.

Results: Compared with placebo, all the treatments studied were highly efficacious (>75%) for the clinical and mycological cure of vulvovaginal candidiasis. Single-day use of 150 mg of fluconazole was slightly more effective than multiple-day topical therapy in early clinical cure both in pairwise (pooled odds ratio=1.9, 95% confidence interval=1.31-2.74, I2=0%) and network meta-analysis (odds ratio=1.52, 95% confidence interval=1.13-2.07) analyses. In the evaluation of late clinical cure, there were no significant differences in the odds ratios of success between oral and topical treatment, either as single or multiple-day therapy (3983 subjects in the network). Single dose fluconazole was marginally superior to multiple-day topical treatment in late mycological cure (odds ratio=1.42, 95% confidence interval=1-1.99). In the ranking analysis, single-day oral fluconazole treatment had the best chance of achieving early (surface under the cumulative ranking curve=74.1%) and late (surface under the cumulative ranking curve=84.2%) mycological cure. Multiple-day treatment with itraconazole scored best in early (surface under the cumulative ranking curve=99%) and late (surface under the cumulative ranking curve=75.7%) relief of symptoms.

Conclusion: Given the high efficacy of both oral and topical drugs, a strict hierarchy of competing treatments for uncomplicated vulvovaginal candidiasis is probably inappropriate; however, current guidelines should acknowledge that oral azoles have a higher chance of clinical success and microbiological eradication of Candida than topical drugs.

Keywords: Candida; azoles; fluconazole; topical drugs; uncomplicated vulvovaginal candidiasis.