Carbon Dioxide Nonablative Laser Compared with Topical Clobetasol for Lichen Sclerosus

OBJECTIVE: To compare nonablative carbon dioxide (CO 2 ) laser treatment with topical clobetasol propionate for symptom control in women with vulvar lichen sclerosus (LS). METHODS: We conducted a prospective, randomized, open-label trial that included women with symptomatic LS. Participants were randomized to three courses of CO 2 laser treatment every 3 weeks or to a 3-month regimen of tapered topical clobetasol propionate 0.05%. The primary outcome was the change in the BIP (burn-itch-pain) score (range 0–30) from baseline to 3 months. Secondary outcomes included physician-rated visual improvement and overall improvement, and disease-specific quality of life (QOL). Ninety participants per group provided 90% power to detect a 2-point between-group BIP score difference (SD 4; 2-sided α=0.05). Analyses were intention-to-treat. Prespecified multivariable linear regression adjusted for baseline symptom severity, age, body mass index (BMI), smoking status, previous corticosteroid use, and disease duration. RESULTS: Between November 2021 and March 2025, 245 women were randomized (laser: n=123; clobetasol propionate: n=122). At 3 months, symptom improvement was greater in the laser group (median ΔBIP score −8 IQR −13 to−3) than in the clobetasol propionate group (−5 IQR, −10.75 to 0; P =.007). In the multivariable analysis, laser treatment remained independently associated with greater symptom improvement (adjusted β, −2.90; 95% CI, −4.64 to −1.15; P =.001). Physician-rated visual improvement and overall improvement, and disease-specific QOL change favored laser therapy. Both treatments were generally well tolerated, with no serious treatment-related adverse events. During an exploratory postrandomization phase after the 3-month primary endpoint assessment, participants could choose to cross over to the alternative treatment. Patients who crossed over from clobetasol propionate to laser experienced additional symptom improvement from 3 to 6 months. Results were robust to sensitivity analyses for missing outcome data. CONCLUSION: Laser treatment resulted in greater symptom improvement than clobetasol propionate therapy for women with vulvar LS. Sequential treatment with clobetasol propionate followed by CO 2 laser may further improve clinical symptoms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05010421.