Adjunctive Panthenol-Enriched Balm during Oral Isotretinoin: Hydration and Barrier Outcomes

INTRODUCTION: Oral isotretinoin is highly effective for moderate-to-severe acne but frequently causes mucocutaneous adverse effects due to epidermal barrier disruption. This study assessed facial hydration, transepidermal water loss (TEWL), selected clinical outcomes, and tolerability when a panthenol-enriched balm was used adjunctively during oral isotretinoin therapy. METHODS: In this randomized, single-center, investigator-blinded, parallel-group study, 70 Chinese patients were assigned 1:1 to a panthenol-enriched balm (Panthenol group) or its vehicle (Vehicle group) during a fixed 56-day oral isotretinoin regimen. TEWL was the registered primary outcome, measured at five facial sites through day 56, and stratum corneum hydration (SCH) was a secondary hydration outcome. The planned sample size was recalculated from the protocol assumptions (between-group difference = 4, common standard deviation [SD] = 4.8, two-sided α = 0.05, power = 90%), giving 32 participants per group. Longitudinal TEWL and SCH were analyzed with reviewer-driven post hoc baseline-adjusted mixed models for repeated measures (MMRM), ordinal outcomes with cumulative-logit models, and day-56 clinical outcomes with baseline-adjusted models, with Holm adjustment within each five-member family. RESULTS: A total of 70 patients were randomized (35 patients per group); 67 contributed to at least one postbaseline observation, and 65 completed day 56 (Panthenol, n = 33; Vehicle, n = 32). None of the five day-56 site-specific TEWL change-from-baseline comparisons were statistically significant after Holm adjustment. A site-specific difference observed in a reviewer-driven post hoc longitudinal analysis was considered exploratory and hypothesis-generating. SCH was higher with the balm at all five sites at day 28 after Holm adjustment (differences, 9.28-11.75 a.u.). At day 56, point estimates remained positive at all five sites, but none were statistically significant after Holm adjustment. Investigator's Global Assessment (IGA) scores improved over time in both groups (P < 0.001), with no evidence of different trajectories (treatment-by-visit, P = 0.884). CONCLUSIONS: Adjunctive use of the panthenol-enriched balm was associated with higher stratum corneum hydration, most evident at day 28. No confirmatory treatment effect was demonstrated for the registered TEWL outcome across facial sites. Further studies with a single prespecified TEWL estimand are warranted. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2400094437 (registered 23 December 2024; first participant enrolled 15 February 2025).