INTRODUCTION
Acne vulgaris is one of the most common chronic dermatologic conditions globally and often significantly affects quality of life. For moderate to severe and treatment-resistant acne, oral isotretinoin remains one of the most effective therapies.1,2 Although isotretinoin is often used short-term, there is increasing interest in prolonged or repeated low-dose therapy and off-label applications for chronic dermatoses. These evolving use patterns have renewed concerns about the drug's long-term safety. A major concern that has been raised in the past was a potential association between isotretinoin use and inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis.3,6 Initial reports were based on case series or claims-based cohort studies, which lacked long-term follow-up, robust adjustment for confounders such as antibiotic exposure, or clinical detail.5,6 More recent studies have questioned the validity of this association and even proposed a potential protective effect of isotretinoin.7,10 However, findings remain inconsistent, and definitive conclusions are lacking. To address this question with greater clarity, we used the TriNetX network to conduct a large retrospective cohort study of acne patients with and without isotretinoin exposure. Our study differs from prior analyses in several ways. First, it utilizes real-world clinical data from multiple health systems and includes not only diagnostic codes, but laboratory values such as fecal calprotectin and low-density lipoprotein (LDL) levels. Unlike earlier studies based solely on administrative claims, our analysis included real-world laboratory data allowing for a more clinically meaningful assessment of intestinal inflammation and metabolic effects.
Second, we evaluated outcomes at 6-12 months, 5 years, and 10 years post-treatment, enabling a more comprehensive view of long-term risk. Finally, we used propensity score matching that controlled for relevant clinical covariates, including prior systemic antibiotic exposure which is a potential confounder that may have biased previous results.
Second, we evaluated outcomes at 6-12 months, 5 years, and 10 years post-treatment, enabling a more comprehensive view of long-term risk. Finally, we used propensity score matching that controlled for relevant clinical covariates, including prior systemic antibiotic exposure which is a potential confounder that may have biased previous results.
