Drug Therapies and the Risk of Malignancy in Crohn's Disease: Results From the TREAT™ Registry

OBJECTIVES: We assessed potential associations between malignancy and antitumor necrosis factor therapy in patients with Crohn's disease (CD), as this relationship is currently poorly defined. METHODS: Utilizing data from the Crohn's Therapy, Resource, Evaluation, and Assessment Tool (TREAT T) Registry, a prospective cohort study examining long-term outcomes of CD treatments in community and academic settings, influences of baseline patient/disease characteristics and medications were assessed by survival analysis and multivariate models. Standardized incidence ratios and exact 95% confidence intervals were determined as the ratio of events observed (TREAT) vs. expected (general population of USA). RESULTS: As of 23 February 2010, 6,273 CD patients (infliximab during registry = 3,420 (during or within 1 year before registry = 3,764); other-treatments-only: 2,509), were enrolled and, on average, had been followed for 5.2/7.6 years, respectively, for all/currently active patients. Crude cancer incidences were similar between infliximab-and other-treatments-only-exposed patients. Multivariate Cox regression analysis demonstrated that baseline age (hazard ratio (HR) = 1.59/10 years; P < 0.001), disease duration (HR = 1.64/10 years; P = 0.012), and smoking (HR = 1.38; P = 0.045) but neither immunosuppressive therapy alone (HR = 1.43; P = 0.11), infliximab therapy alone (HR = 0.59; P = 0.16), nor their combination (HR = 1.22, P = 0.34) were independently associated with the risk of malignancy. When compared with the general population, no significant increase in incidence was observed in any malignancy category. In an exposure-based analysis, use of immunosuppressants alone (odds ratio = 4.19) or in combination with infliximab (3.33) seemed to be associated with a numerically, but not significantly, greater risk of malignancy than did treatment with infliximab alone (1.96) relative to treatment with neither. CONCLUSIONS: In the TREAT Registry, age, disease duration, and smoking were independently associated with increased risk of malignancy. Although results for immunosuppressant use were equivocal, no significant association between malignancy and infliximab was observed.