Cancer Incidence in Patients with Ulcerative Colitis Naïve to or Treated with Thiopurine and Targeted Therapies- a cohort study 2007 to 2022 with comparison to the general population.

in Journal of Crohn's & colitis by Åsa H Everhov, Johan Askling, Jonas Söderling, Jonas Halfvarson, Julia Eriksson, , Karin E Smedby, Jonas F Ludvigsson, Henrik Toft Sørensen, Ola Olén

TLDR

  • The study found that patients with ulcerative colitis receiving modern-day treatments have an increased risk of developing cancer, with rates highest in those ≥60 years old.

Abstract

Cancer incidence data including absolute risk differences are needed for clinical risk communication to patients receiving modern-day treatments for ulcerative colitis (UC). We linked nationwide Swedish health registers and assessed incident cancers in patients with UC in 2007-2022. We computed age-stratified incidence rates (IRs), IR differences and hazard ratios (HRs) in a naïve cohort with no immunomodulatory treatment, and in cohorts treated with thiopurine or targeted therapies. General population comparator subjects were matched (by age, sex, calendar year, and area of residence) to each treatment cohort. We used a once-exposed - always exposed design. We identified 63,925 patients with UC in partly overlapping cohorts and 593,072 comparators with a total follow-up time of 5,800,089 years (median 8.1 years).The IRs were elevated compared to the general population in naïve patients: 2.7 extra cancer cases per 1000 person years (HR:1.12, 95%CI:1.09-1.16), in thiopurine-treated patients: 3.4 extra cases (HR:1.48;1.37-1.61), TNFi-treated: 2.7 extra cases (HR:1.41;1.24-1.62), Thiopurine+TNFi-treated: 2.42 extra cases (HR:1.44;1.19-1.75), vedolizumab-treated: 2.88 extra cases (HR:1.27;0.90-1.79). The IR differences were not significantly increased in patients treated with ustekinumab 0.57 (HR:0.87;0,39-1.93) and tofacitinib -0.69 (HR:0.84;0.25-2.77). Across all treatment groups, the IR differences compared to the general population were highest in patients ≥60 years. The differences were driven by colorectal cancer, hepatobiliary cancer, lymphoma, and basal cell skin carcinoma. Elevated cancer incidence was observed in patients with UC amounting to around 3 extra cases of cancer per 1000 years. Cancer risks varied more among groups defined by age than by treatment.

Overview

  • The study aimed to investigate the incidence of cancer in patients with ulcerative colitis (UC) receiving modern-day treatments and to provide absolute risk differences for clinical risk communication.
  • The researchers linked nationwide Swedish health registers and assessed incident cancers in patients with UC from 2007-2022, including age-stratified incidence rates, incidence rate differences, and hazard ratios.
  • The study included 63,925 patients with UC and 593,072 general population comparator subjects, with a total follow-up time of 5,800,089 years (median 8.1 years).

Comparative Analysis & Findings

  • The incidence rates were elevated compared to the general population in patients with UC, with a hazard ratio (HR) of 1.12 in naïve patients, 1.48 in thiopurine-treated patients, 1.41 in TNFi-treated patients, 1.44 in patients treated with both thiopurine and TNFi, and 1.27 in patients treated with vedolizumab.
  • The incidence rate differences were not significantly increased in patients treated with ustekinumab (HR:0.87) and tofacitinib (HR:0.84).
  • Across all treatment groups, the incidence rate differences compared to the general population were highest in patients ≥60 years, driven by colorectal cancer, hepatobiliary cancer, lymphoma, and basal cell skin carcinoma.

Implications and Future Directions

  • The study's findings highlight the importance of discussing cancer risks with patients with UC receiving modern-day treatments, particularly those ≥60 years old.
  • Future studies could investigate the mechanisms underlying the observed cancer risks and explore potential biomarkers for identifying patients at high risk.
  • The study's results also underscore the need for regular cancer surveillance in patients with UC and the importance of incorporating this into clinical practice.
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