Vulvar Fractionated CO2-Laser Therapy With and Without Concomitant Topical Clobetasol Propionate 0.05% Ointment for Treatment of Vulvar Lichen Sclerosus (VULVIE): A Randomized Controlled Trial

INTRODUCTION: Lichen sclerosus (LS) is a chronic, debilitating vulvar skin condition. Patients with LS often endure physical discomfort, isolation, and loss of intimate relationships before obtaining ultrapotent topical corticosteroid (TCS) treatment. Fractionated CO2 laser (FxCO2-laser) has shown promising results in improving LS by increasing collagen, elastin, and vascularity. It may also increase topical drug permeation, potentially augmenting the effect of TCS. OBJECTIVE: To compare change in condition-specific quality of life (QOL) in women with LS treated with FxCO2-laser and clobetasol propionate 0.05% (TCS) versus FxCO2-laser alone. METHODS: This randomized, single-blind, placebo-controlled trial was conducted at nine SGS CoRPS investigator sites across the US from 3/2022 to 3/2025. English- or Spanish-speaking adults with clinically diagnosed LS electing FxCO2-laser treatment were recruited. Women with prior vaginal mesh prolapse surgery, laser/topical immunomodulator/systemic therapy for LS, vulvar/vaginal malignancy, pelvic radiation, poor wound healing/keloids, and those currently lactating/pregnant, undergoing treatment for malignancy, with an active genital infection, or with an unevaluated suspicious vulvar lesion were excluded. Women on TCS underwent a 2-week washout prior to trial initiation and baseline assessments. Participants underwent three FxCO2-laser treatments 4–6 weeks apart and completed assessments at baseline and approximately 1 month after the third (final) FxCO2-laser treatment. Participants were instructed to apply 0.25–0.5 g of study ointment to the affected tissues nightly for 4 weeks starting after the first FxCO2-laser treatment and then continue applying twice a week until study completion. The primary outcome was the Skindex-29 questionnaire total score, which ranges from 0 (no effect) to 100 (effect experienced all the time) and contains the three domain scores (symptoms, emotions, and functioning), which were also used to measure LS-related QOL. Participants were randomized 1:1 to either TCS (FxCO2-laser+TCS) or control (FxCO2-laser alone) treatment in random permutated blocks stratified by site and prior LS therapy utilizing REDCap for allocation concealment. Estimated sample size was 184 participants to detect a 20% difference in the total Skindex-29 score change of ≥16 between arms. RESULTS: In total, 201 participants were randomized (103 TCS; 98 control). There were no significant differences in baseline characteristics (Table 1). Most participants had been treated with TCS previously with about half of all participants having experienced LS symptoms for over 5 years. Nearly one third of participants met our definition for condition-specific QOL improvement with a total Skindex-29 score decrease of ≥16, with no significant difference between arms (28% control vs 31% TCS, p=0.67). Compared to controls, the TCS arm showed a significantly greater improvement in total Skindex-29 scores (change of −8.1±15.5 control vs −13.0±15.9 TCS, p=0.04) and symptom domain score (change of −10.1±19.8 control vs −19.0±18.5 TCS, p<0.01; Table 2). CONCLUSIONS: FxCO2-laser treatment improved condition-specific QOL in patients with LS, regardless of concomitant TCS therapy. Although there was no difference in our primary outcome, participants undergoing concomitant TCS showed significantly greater improvement in overall QOL and in LS-specific symptoms. These data provide compelling evidence that FxCO2-laser may augment TCS absorption. Further research is needed to determine optimal treatment strategies for women with LS.Table 1Table 2