Safety and Predictors of Clinically Significant Adverse Effects of Isotretinoin in Acne Vulgaris: A Retrospective Cohort Study from Saudi Arabia.

PURPOSE: Isotretinoin remains the most effective treatment for moderate-to-severe acne vulgaris; however, its use is frequently associated with mucocutaneous and metabolic adverse effects that may necessitate active clinical intervention. Data evaluating predictors of clinically significant toxicity in Saudi populations remain limited. PATIENTS AND METHODS: A retrospective cohort study was conducted at a tertiary academic hospital in Saudi Arabia. Electronic medical records of patients with acne vulgaris treated with isotretinoin between January 2020 and December 2024 were reviewed. Demographic variables, acne severity, isotretinoin dosing characteristics, laboratory findings, adverse effects, management strategies, and treatment outcomes were extracted. Multivariable regression analysis was performed to identify predictors of adverse effects requiring clinical intervention. RESULTS: A total of 444 patients were included. Most participants were aged 21-30 years (60.4%), and females represented 50.9% of the cohort. Clinical intervention was required in 70.7% of patients, including supportive care, treatment reduction and dose discontinuation to manage isotretinoin-related adverse effects. Mucocutaneous adverse effects, particularly cheilitis and xerosis, were the most frequently documented complications. Laboratory abnormalities were observed less frequently, although elevated LDL levels were identified in 9.9% of patients, followed by elevated total cholesterol (7.2%) and triglycerides (4.5%). Elevated liver enzymes were relatively uncommon (AST 4.1%, ALT 3.2%). Higher cumulative dose, dose escalation during therapy, and higher maximum dose significantly increased the likelihood of requiring clinical intervention. Female sex and higher body weight were associated with lower odds of intervention. Major improvement was achieved in 37.4%, complete clearance in 28.8%, giving a combined rate of 66.2% while recurrence after discontinuation occurred in 19.4%. CONCLUSION: Isotretinoin, proved efficacious clinically in the management of acne vulgaris, however was identified to be associated with high number of adverse effects which require active management. Multivariable regression identified that the increasing dose and cumulative dose were the most influential determinants of the drug therapy. Particularly, lipid abnormalities (elevated LDL) were clinically relevant for the included cohort of patients. The outcomes therefore emphasize the need for a personalised approach to dosing along with continuous monitoring to achieve the optimal results.