No Increased Mortality Hazard Among High-Dose Topical and Oral Isotretinoin Users: Revisiting the VATTC

Topical and oral retinoids are widely used in dermatology for acne and photoaging. Concern regarding a possible increase in all-cause mortality emerged after the VA Topical Tretinoin Chemoprevention Trial reported excess deaths among older patients receiving high-potency topical tretinoin. Subsequent analyses reinforced this signal, leading to caution in prescribing high-strength topical retinoids despite limited confirmatory data in younger acne populations.

A retrospective cohort study was conducted using the TriNetX Research Network. Two propensity score matched analyses compared acne patients treated with oral isotretinoin or topical tretinoin 0.1% with acne patients without retinoid exposure. Cohorts were matched 1 to 1 using demographic and clinical covariates. The primary outcome was all-cause mortality. Risk-based and time-to-event analyses were performed.

After matching, 13,891 isotretinoin users and 8,070 topical tretinoin users were analyzed alongside matched controls. Oral isotretinoin was associated with a lower absolute mortality risk compared with controls, although no significant difference was observed in time-to-event analysis. Topical tretinoin showed no difference in mortality risk or survival. Subgroup analyses stratified by age and sex demonstrated no increased mortality risk.

Neither oral isotretinoin nor high-potency topical tretinoin was associated with increased all-cause mortality in acne patients. These findings provide reassurance for clinicians prescribing retinoids in routine dermatologic care.