Increased risk of inflammatory bowel disease among patients treated with rituximab in Iceland from 2001 to 2018

Abstract

Objective

Immune-mediated diseases are on the rise after the introduction of powerful immunomodulating drugs. The objective of this study was to determine the population-based incidence rate of inflammatory bowel disease (IBD) among patients treated with the monoclonal antibody rituximab in Iceland and compare it to the baseline incidence rate of IBD in the general population.

Methods

We identified all patients treated with rituximab in Iceland from 2001 to 2018 through a central medicine database. IBD cases were indexed from medical records and ICD-10 codes and further confirmed by colonoscopy- and pathology reports. An experienced pathologist compared the pathology of IBD cases with matched controls of IBD patients.

Results

Lymphomas and related neoplasms were the most frequent indication for treatment with rituximab (n = 367) among the 651 patients included in the analysis. Following treatment, seven patients developed IBD: two cases of Crohn’s disease, three with ulcerative colitis, and two with indeterminate IBD. The incidence rate of IBD among rituximab treated patients was 202 cases per 100,000 person-years. Comparing our data to IBD incidence in Iceland, rituximab treated patients have an age-adjusted hazard ratio of 6.6 for developing IBD. The risk did not correlate with dose or treatment duration. Prior diagnosis of an autoimmune illness did not increase the risk of IBD in rituximab treated patients.

Conclusions

Patients on rituximab have a sixfold increased risk of developing IBD compared to the general population. This risk was not affected by the indication for treatment and was not associated with concurrent immune-mediated diseases.

Summary

• This population-based retrospective cohort study included all patients receiving treatment with rituximab between 2001 and 2018 in Iceland and identified a sixfold increased risk of developing IBD when compared to the general population.

Keywords:

• Immunology
• IBD-clinical
• IBD-basic
• colonic-disorders
• endoscopy-general

Acknowledgments

The authors are grateful to Ingibjörg Richter, data analyst, for her support in obtaining various forms of data and Rannveig Einarsdottir, pharmacist, for giving access to rituximab use in Iceland.

Disclosure statement

No potential conflict of interest was reported by the author(s).