Oteseconazole for acute and recurrent vulvovaginal candidiasis: A systematic review, meta-analysis, and trial sequential analysis of randomized trials.

ObjectivesVulvovaginal candidiasis and its recurrent vulvovaginal candidiasis form place a significant burden on women worldwide. However, treatment options remain limited. Oteseconazole, a first-in-class tetrazole CYP51 inhibitor that received Food and Drug Administration approval for recurrent vulvovaginal candidiasis in 2022, has not yet had its comparative efficacy against fluconazole in acute vulvovaginal candidiasis systematically synthesized. In addition, the full scope of evidence for its maintenance use has not been formally synthesized. Using a dual-Population-Intervention-Comparator-Outcome (PICO) framework, this systematic review and meta-analysis aimed to: (a) evaluate whether oteseconazole provides superior efficacy to fluconazole in acute vulvovaginal candidiasis; (b) comprehensively synthesize maintenance efficacy and safety outcomes in recurrent vulvovaginal candidiasis; and (c) assess the certainty and sufficiency of the available evidence using Grading of Recommendations Assessment, Development, and Evaluation and trial sequential analysis.MethodsThis systematic review and meta-analysis was prospectively registered with PROSPERO (registration number: CRD420261331936). A systematic search of PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov was conducted without date or language restrictions. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Meta-analyses were performed using random-effects models with restricted maximum likelihood estimation and Hartung-Knapp-Sidik-Jonkman correction.ResultsA total of five unique randomized controlled trials (six PICO-level inclusions) were included, enrolling 596 participants across PICO 1 and 1090 across PICO 2. In acute vulvovaginal candidiasis (PICO 1, two trials, n = 361), oteseconazole was associated with a significantly higher therapeutic cure rate (composite clinical and mycological cure) at day 28 than fluconazole (risk ratio = 1.39, 95% confidence interval: 1.13 to 1.71; p = 0.002). Significant improvements were also observed in clinical cure at day 28 (risk ratio = 1.28, 95% confidence interval: 1.09 to 1.51; p = 0.003) and mycological cure at both day 14 (risk ratio = 1.24, 95% confidence interval: 1.09 to 1.41; p = 0.001) and day 28 (risk ratio = 1.38, 95% confidence interval: 1.20 to 1.58; p < 0.001). In recurrent vulvovaginal candidiasis prevention (PICO 2, four trials, n = 959), oteseconazole significantly reduced culture-confirmed recurrence at weeks 48-50 (risk ratio = 0.13, 95% confidence interval: 0.09 to 0.19) and week 24 (risk ratio = 0.10, 95% confidence interval: 0.07 to 0.15) and substantially prolonged the time to first recurrence (hazard ratio = 0.09, 95% confidence interval: 0.05 to 0.14), all with zero heterogeneity. Furthermore, trial sequential analysis confirmed that the cumulative evidence surpassed the required information size for both recurrence time points. Safety outcomes were comparable between groups in both settings.ConclusionsIn patients with recurrent vulvovaginal candidiasis, oteseconazole demonstrated favorable outcomes by significantly reducing recurrent infections while maintaining a comparable safety profile, supporting its use as a maintenance regimen. However, the evidence supporting its role in acute vulvovaginal candidiasis remains limited.