Absolute Risk of Malignancy by Treatment in Patients With Crohn's Disease Compared with the General Population: A Nationwide Population-Based Cohort Study.

INTRODUCTION

Real-world data quantifying absolute cancer risk in Crohn's disease (CD) by treatment status are lacking but are essential for patient counselling.

METHODS

We linked nationwide Swedish register data and assessed incident cancers overall and by type in patients with CD 2007-2023. We estimated age-stratified incidence rate (IR) differences compared with the general population in a once-exposed-always-exposed design. Treatment cohorts comprised new users of thiopurine, tumor necrosis factor inhibitors (TNFi), thiopurine + TNFi, vedolizumab, ustekinumab, and patients naïve to immunomodulatory drugs.

RESULTS

We followed 38,733 patients and 360,616 comparator subjects for a median 7.3 years. The IR differences for any cancer (number of excess cancers in each treatment cohort per 1,000 person-years versus the matched population) were 2.43 (95% CI: 1.92; 2.94) for the naive cohort; 3.14 (95% CI: 2.50; 3.78) for thiopurine-treated, 2.42 (95% CI: 1.63; 3.22) for TNFi-treated, 2.59 (95% CI: 1.53; 3.64) for thiopurine + TNFi, 2.61 (95% CI: -0.08; 5.30) for vedolizumab, and 1.54 (95% CI: -1.34; 4.41) for ustekinumab. The excess cancer incidence was primarily because of nonmelanoma skin cancer (squamous cell and basal cell carcinoma). After exclusion of nonmelanoma skin cancers, the excess overall cancer incidence was 1.27 to 0.96 cases/1,000 person-years in the naïve, thiopurine, and TNFi-treated groups, but not significantly increased in the other. IR differences for overall cancer increased and hazard ratios decreased with increasing patient age.

DISCUSSION: Elevated overall cancer incidence was observed across all treatment cohorts, also in treatment-naïve patients. After exclusion of nonmelanoma skin cancer, the excess cancer incidence in CD was around 1 extra case per 1,000 person-years because of lung, small bowel, hepatobiliary, and hematologic cancers.