Efficacy of antifungal drugs in the treatment of vulvovaginal candidiasis: a Bayesian network meta-analysis

Abstract

Purpose: Antifungal drugs are used frequently in the treatment of vulvovaginal candidiasis (VVC), but have shown controversial results. In this study, we aimed to evaluate the effectiveness of different antifungal drugs in the treatment of VVC and to provide an evidence-based reference for clinical use.

Methods: The published studies on the effectiveness of antifungal drugs in the treatment of VVC (up to April 2018) were retrieved from PubMed, Embase, the Cochrane Library, and Clini-calTrials.gov. We sifted through the literature according to Patients, Interventions, Comparisons and Outcomes principle, extracted data on the basic characteristics of the study, and evaluated the quality of included studies. We used R software for statistical analysis.

Results: In total, 41 randomized controlled trials were included in this meta-analysis. The relative risk of VVC associated with ten drugs, including placebo, fluconazole, clotrimazole, miconazole, itraconazole, ketoconazole, econazole, butoconazole, terbinafine, and terconazole, was analyzed. The following drugs appeared to show more efficacy than placebo in the treated patients: fluconazole (OR =6.45, 95% CrI 4.42-9.41), clotrimazole (OR =2.99, 95% CrI 1.61-5.55), miconazole (OR =5.96, 95% CrI 3.17-11.2), itraconazole (OR =2.29, 95% CrI 1.21-4.33), ketoconazole (OR =2.40, 95% CrI 1.55-3.71), butoconazole (OR =1.18, 95% CrI 1.06-1.31), and terconazole (OR =5.60, 95% CrI 2.78-11.3). The value of surface under the cumulative ranking curve of each drug was as follows: placebo (0.5%), fluconazole (91.5%), clotrimazole (61.8%), miconazole (33.8%), itraconazole (50.5%), ketoconazole (42.8%), econazole (46.8%), butoconazole (82.2%), terbinafine (20.9%), and terconazole (65.0%).

Conclusion: Antifungal drugs are effective in the treatment of VVC. Fluconazole appeared to be the best drug for the treatment of VVC according to our analysis.

Keywords: antifungal drugs; network meta-analysis; randomized controlled trials; vulvovaginal candidiasis.

Figure 1

Flow diagram of the study selection process.

Figure 2

Risk of bias of the included randomized controlled trials (review authors’ judgments about each risk-of-bias item for each included study). Note: +, low risk; −, high risk; ?, unclear risk.

Figure 3

Network of randomized controlled trials comparing different antifungal drugs for vulvovaginal candidiasis treatment. Note: The thickness of the connecting lines represents the number of trials between each comparator, and the size of each node corresponds to the number of subjects who received the same pharmacological agent (sample size) (A: placebo; B: fluconazole; C: clotrimazole; D: miconazole; E: itraconazole; F: ketoconazole; G: econazole; H: butoconazole; I: terbinafine; J: terconazole).

Figure 4

Surface under the cumulative ranking curve (SUCRA), expressed as percentages, ranking the therapeutic effects and safety of treatments for vulvovaginal candidiasis. Note: For efficacy and safety assessment, the pharmacological agent with the highest SUCRA value would be the most efficacious and safe treatment (A: placebo; B: fluconazole; C: clotrimazole; D: miconazole; E: itraconazole; F: ketoconazole; G: econazole; H: butoconazole; I: terbinafine; J: terconazole).

Figure 5

Comparison-adjusted funnel plot for the network meta-analysis. Notes: The red line suggests the null hypothesis that the study-specific effect sizes do not differ from the respective comparison-specific pooled effect estimates. Different colors represent different comparisons (A: placebo; B: fluconazole; C: clotrimazole; D: miconazole; E: itraconazole; F: ketoconazole; G: econazole; H: butoconazole; I: terbinafine; J: terconazole).