Mortality Associated With Development of Squamous Cell Cancer in Patients With Inflammatory Bowel Diseases Receiving Treatment With Thiopurines.

Background & Aims: Treatment with thiopurines is associated with an increased risk of squamous cell carcinoma of the skin (SCC) in patients with inflammatory bowel diseases (IBD). We studied outcomes of patients with IBD who developed SCC while receiving thiopurine therapy.

Methods: We conducted a retrospective cohort study of 54,919 patients with IBD followed in the nationwide Veterans Affairs Healthcare System from January 1, 2000, through May 23, 2018. From this cohort, we created a sub-cohort of patients with an incident diagnosis of SCC, confirmed by review of patients' medical records; we identified those who had received treatment with thiopurines (exposed group) vs those treated with mesalamine and no prior exposure to thiopurines or tumor necrosis factor antagonists (unexposed group). The primary outcome was death associated with SCC (SCC mortality). We collected data on baseline demographic features, exposure to ultraviolet light, Charlson comorbidity index, smoking status, and environmental exposures. Follow up began at the time of incident SCC diagnosis and ended at death or last recorded date in the health system. Cause-specific hazard models were used to estimate the adjusted and unadjusted hazard ratio (HRs), with 95% CIs, for SCC mortality.

Results: We identified 467 patients with incident SCC and included 449 patients (161 exposed and 288 unexposed) in our final analysis. Eleven patients from complications of SCC (8 in the exposed group and 3 in the unexposed group). The estimated 5- and 10-year cumulative mortality values were 2.9% and 2.9% in the exposed group and 0.4% and 0.9% in the unexposed group, respectively. The unadjusted and adjusted cause-specific HRs for SCC mortality associated with exposure were 7.0 (95% CI, 1.8-28.0; P = .006) and 8.0 (95% CI, 2.0-32.8; P = .004), respectively.

Conclusions: Although the cause-specific mortality is relatively low, patients with IBD exposed to thiopurines who develop SCC have an increased risk of SCC-associated death compared to patients exposed to only mesalamine.