Comparative effectiveness of cryotherapy, low-dose oral isotretinoin, and combination therapy for digital verruca vulgaris: a multicenter real-world cohort study.

BACKGROUND: Comparative real-world evidence on cryotherapy, low-dose oral isotretinoin, and their combination for digital verruca vulgaris remains limited. METHODS: We conducted a retrospective multicenter cohort study of 393 adults treated with cryotherapy (n = 136), isotretinoin (n = 130), or combination therapy (n = 127) from 2022 to 2025. Outcomes included complete clearance by 3, 6, and 12 months, patient-reported outcomes, 12-month follow-up visit completion, and safety. Analyses used multivariable logistic regression, generalized estimating equations, and overlap-weighted propensity score sensitivity analyses. RESULTS: Complete clearance differed across groups by 3 months (54.4% cryotherapy, 60.0% isotretinoin, 75.6% combination; p = 0.001), 6 months (64.7%, 70.8%, 85.0%; p < 0.001), and 12 months (67.6%, 75.4%, 88.2%; p < 0.001). Adjusted models favored combination therapy versus cryotherapy at all timepoints and versus isotretinoin by 6 and 12 months; overlap-weighted analyses were directionally consistent. TSQM effectiveness and global satisfaction were higher with combination therapy. Treatment-emergent adverse events were more frequent with isotretinoin-containing regimens, with no Grade 3 or higher AST/ALT elevations reported. CONCLUSION: Combination therapy was associated with higher observed clearance than either monotherapy in real-world practice. Given the non-randomized design and follow-up attrition, prospective randomized trials are needed to establish comparative effectiveness.