Isotretinoin and Risk of Inflammatory Bowel Disease
Isotretinoin and Risk of Inflammatory Bowel Disease
Objectives: Isotretinoin, a drug widely prescribed for severe acne, has been suspected to increase the risk of ulcerative colitis (UC), but data are conflicting. To further examine the association between isotretinoin use and risk for UC and Crohn's disease (CD), we conducted a large nationwide case–control study in France.
Methods: We used information from the National Health Insurance system for all French people covered by the general scheme between 1 January 2008 and 31 December 2010, totaling over 50 million individuals (i.e., 76% of the whole French population). All incident claims for UC and CD and all medical drug reimbursements were automatically recorded in the database. For each case, four controls were matched on age, gender, year of enrollment, and follow-up duration. The association between isotretinoin use and UC or CD claim was estimated by conditional logistic regression.
Results: We included 7,593 cases of inflammatory bowel disease (IBD; 3,187 UC, 4,397 CD, and 9 indeterminate colitis) and 30,372 controls; among them, 26 cases (0.3%) (15 UC (0.5%) and 11 CD (0.3%)) and 140 controls (0.4%) were exposed to isotretinoin. Isotretinoin exposure was not associated with an increased risk for UC (odds ratio (OR)=1.36 (95% confidence intervals (CI): 0.76, 2.45)) but was associated with a decreased risk for CD (OR=0.45 (95% CI: 0.24, 0.85)), P value for homogeneity between UC and CD=0.001. Results were similar in analyses restricted to individuals below the age of 40 years, to cases with colonoscopy or intestinal surgery, or when adjusting for other acne treatments.
Conclusions: In this population-based case–control study, isotretinoin use was not associated with increased UC risk but was associated with a decreased CD risk. This study provides reassuring data for people using isotretinoin.
Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory intestinal bowel diseases (IBD) characterized by an abnormal composition of the intestinal microbiota, a deregulated activation of intestinal cellular immunity, and an overproduction of pro-inflammatory cytokines. There appears to be no single etiology for these diseases but rather predisposing genetic and environmental factors. Prospective cohort studies have shown that drugs such as antibiotics, nonsteroidal anti-inflammatory drugs, and hormone therapy are associated with an increased risk for IBD. Isotretinoin, a vitamin A analog prescribed in severe acne, has also been suspected to increase the risk for IBD. Several cases of IBD following prescription of isotretinoin have been reported. One case–control study found a positive association between isotretinoin and UC. However, this was not confirmed in other studies and a potential confounding effect of tetracycline antibiotics used to treat acne has been suggested. This issue is important. Indeed, isotretinoin is widely prescribed to treat severe acne; physicians and patients should be informed of the increased risk of IBD, if it exists. Moreover, the discovery of a new environmental factor may add to the understanding of the etiological puzzle of IBD and may possibly lead to new therapeutic pathways. Therefore, to further evaluate the association between isotretinoin intake and IBD risk, we performed a nationwide case–control study using two large French databases of the National Health Insurance (NHI) system.
Abstract and Introduction
Abstract
Objectives: Isotretinoin, a drug widely prescribed for severe acne, has been suspected to increase the risk of ulcerative colitis (UC), but data are conflicting. To further examine the association between isotretinoin use and risk for UC and Crohn's disease (CD), we conducted a large nationwide case–control study in France.
Methods: We used information from the National Health Insurance system for all French people covered by the general scheme between 1 January 2008 and 31 December 2010, totaling over 50 million individuals (i.e., 76% of the whole French population). All incident claims for UC and CD and all medical drug reimbursements were automatically recorded in the database. For each case, four controls were matched on age, gender, year of enrollment, and follow-up duration. The association between isotretinoin use and UC or CD claim was estimated by conditional logistic regression.
Results: We included 7,593 cases of inflammatory bowel disease (IBD; 3,187 UC, 4,397 CD, and 9 indeterminate colitis) and 30,372 controls; among them, 26 cases (0.3%) (15 UC (0.5%) and 11 CD (0.3%)) and 140 controls (0.4%) were exposed to isotretinoin. Isotretinoin exposure was not associated with an increased risk for UC (odds ratio (OR)=1.36 (95% confidence intervals (CI): 0.76, 2.45)) but was associated with a decreased risk for CD (OR=0.45 (95% CI: 0.24, 0.85)), P value for homogeneity between UC and CD=0.001. Results were similar in analyses restricted to individuals below the age of 40 years, to cases with colonoscopy or intestinal surgery, or when adjusting for other acne treatments.
Conclusions: In this population-based case–control study, isotretinoin use was not associated with increased UC risk but was associated with a decreased CD risk. This study provides reassuring data for people using isotretinoin.
Introduction
Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory intestinal bowel diseases (IBD) characterized by an abnormal composition of the intestinal microbiota, a deregulated activation of intestinal cellular immunity, and an overproduction of pro-inflammatory cytokines. There appears to be no single etiology for these diseases but rather predisposing genetic and environmental factors. Prospective cohort studies have shown that drugs such as antibiotics, nonsteroidal anti-inflammatory drugs, and hormone therapy are associated with an increased risk for IBD. Isotretinoin, a vitamin A analog prescribed in severe acne, has also been suspected to increase the risk for IBD. Several cases of IBD following prescription of isotretinoin have been reported. One case–control study found a positive association between isotretinoin and UC. However, this was not confirmed in other studies and a potential confounding effect of tetracycline antibiotics used to treat acne has been suggested. This issue is important. Indeed, isotretinoin is widely prescribed to treat severe acne; physicians and patients should be informed of the increased risk of IBD, if it exists. Moreover, the discovery of a new environmental factor may add to the understanding of the etiological puzzle of IBD and may possibly lead to new therapeutic pathways. Therefore, to further evaluate the association between isotretinoin intake and IBD risk, we performed a nationwide case–control study using two large French databases of the National Health Insurance (NHI) system.