Maintenance pharmacological therapy of recurrent vulvovaginal candidiasis. A Bayesian network meta-analysis of randomized studies

Abstract

Objective: Several topical and oral drugs are available for maintenance therapy of recurrent vulvovaginal candidiasis (RVVC)(≥ 3 episodes of symptomatic Candida infection per year). The study aimed to assess the risk of early (24 weeks) and late (48-52 weeks) clinical and mycological recurrences associated with oral/topical pharmacological maintenance therapy of RVVC.

Methods: Search strategy: PubMed, EMBASE, Cochrane Library, OVID and clinical trials registers,from inception until January 2024.

Selection criteria: Blinded and unblinded randomized studies of pharmacological prevention of RVVC recurrences during active treatment and after discontinuation of therapy.

Data collection and analysis: Risk of bias, indirectness, imprecision, heterogeneity and incoherence of the network were evaluated by a semi-automated software.Bayesian network meta-analysis was used to evaluate effects of interventions on outcomes,league table and ranking of effects.

Results: The network included 17 studies with 2304 women for early and 2179 for late recurrences. During active treatment weekly oral oteseconazole (OR = 0.05,95 %CI = 0.02-0.12, moderate confidence),weekly oral fluconazole/itraconazole (OR = 0.12,95 %CI = 0.052-0.35,moderate confidence) and weekly topical clotrimazole (OR = 0.087,95 %CI = 0.018-0.48,moderate confidence) were associated with a significant reduction in RVVC recurrence risk compared to placebo/untreated subjects.Weekly use of fluconazole/itraconazole (OR = 0.44,95 %CI = 0.24-0.80,moderate confidence) and monthly topical treatment (OR = 0.34,95 %CI = 0.18-0.66,moderate confidence) maintained efficacy after discontinuation of therapy (48-52 weeks). Weekly oteseconazole was significantly more effective in reducing the occurrence of late clinical (OR = 0.065,95 %CI = 0.036-0.11,moderate confidence) and mycological (OR = 0.073,95 %CI = 0.044-0.12,moderate confidence) RVVC recurrences than all other types of treatment tested.

Conclusions: Weekly maintenance therapy with oral fluconazole/itraconazole,oteseconazole, or topical clotrimazole was equally effective in preventing early RVVC recurrence.After therapy discontinuation, oteseconazole outperformed all other oral or topical regimens, lowering RVVC clinical and mycological recurrence rates by more than 90%.

Keywords: Candida; Oral azoles; Recurrent vulvovaginal Candiasis; Topical treatment; Vaginal candidosis.