Gastroenterology

Gastroenterology

Volume 145, Issue 5, November 2013, Pages 1007-1015.e3
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Risk of Lymphoma in Patients With Ulcerative Colitis Treated With Thiopurines: A Nationwide Retrospective Cohort Study

https://doi.org/10.1053/j.gastro.2013.07.035Get rights and content

Background & Aims

There is controversy over whether the treatment of patients with ulcerative colitis (UC) with thiopurines increases their risk of lymphoma. We evaluated the risk of lymphoma (ongoing, residual, and per year of therapy) among thiopurine-treated patients with UC.

Methods

We obtained nationwide data from the Veterans Affairs (VA) health care system from 2001 to 2011. We performed a retrospective cohort study, analyzing data on 36,891 patients from their date of diagnosis of UC in the VA health care system to a diagnosis of lymphoma or October 1, 2011 (subjects followed up for a median of 6.7 years). Thiopurine exposure was assessed using the VA pharmacy database. Patients who developed lymphoma were identified based on ICD-9 codes and confirmed by manual chart review.

Results

In total, 4734 patients with UC (13%) were treated with thiopurines for a median of 1 year. Lymphoma developed in 119 patients who had not been treated with thiopurines, 18 who were treated with thiopurines, and 5 who had discontinued treatment with thiopurines. The incidence rates of lymphoma were 0.60 per 1000 person-years among patients who had not been treated with thiopurines, 2.31 among patients who were treated with thiopurines, and 0.28 among patients who had discontinued treatment with thiopurines. The incidence rates of lymphoma during the first year, second year, third year, fourth year, and >4 years of thiopurine therapy were 0.9, 1.6, 1.6, 5, and 8.9 per 1000 person-years, respectively. The age-, sex-, and race-adjusted hazard ratios of developing lymphoma were 4.2 (95% confidence interval, 2.5–6.8; P < .0001) while being treated with thiopurines and 0.5 (95% confidence interval, 0.2–1.3; P = .17) after discontinuing treatment with thiopurines compared with patients who had not been treated with thiopurines.

Conclusions

Based on a retrospective, nationwide cohort study, patients with UC have a 4-fold increase in risk of lymphoma while being treated with thiopurines compared with patients who have not been treated with thiopurines. The risk increases gradually for successive years of therapy. Discontinuing thiopurine therapy reduces the risk of lymphoma.

Section snippets

Study Population

Nationwide data were obtained from the VA Pharmacy Benefits Management and Corporate Data Warehouse databases. Veterans who were seen and followed up in the VA health care system from October 1, 2001, to October 1, 2011, were identified using the International Classification of Diseases, Ninth Revision (ICD-9) codes for UC (556.xx). The study was approved by the institutional review board of the Southeast Louisiana Veterans Health Care System.

Study Design

We conducted a retrospective cohort study in which

Results

We identified 37,191 patients with UC followed up in the VA system during the observational period. A total of 325 patients had diagnostic codes for lymphoma in their records. Manual chart review confirmed 253 cases of lymphoma (among them, 111 prevalent cases of lymphoma were excluded). We included only cases of incident lymphoma (occurring during the follow-up period) confirmed by manual chart review in our analysis. Among the remainder of the patients with a diagnostic code for lymphoma, we

Discussion

In this nationwide cohort of patients with UC from the VA health care system, treatment with thiopurines was associated with an approximate 4-fold and 7-fold increase in the risk of lymphoma relative to patients with UC who were not treated with thiopurines and the SEER general population, respectively. These findings are consistent with the previous population-based prospective cohort study reported by Beaugerie et al in 2009.21 Additionally, we have shown that the magnitude of this risk is

Acknowledgments

The study sponsor (the Departmental of Veterans Affairs) has no role in study design analysis, and interpretation of the data and in the writing of the report. The contents of this report do not represent the views of the Department of Veterans Affairs or the US Government.

The authors acknowledge the kind support of Joel and Nancy Barnett Foundation.

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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research & Development Health Services (VA Project No. 425).

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