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

BACKGROUNDTopical 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.

METHODSA 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.

RESULTSAfter 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.

CONCLUSIONNeither 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.

Abstract from PubMed