The risk of lymphoma and immunomodulators in patients with inflammatory bowel diseases: Results from a population-based cohort in Eastern Europe

Abstract

Background and aims: Prior studies suggest a small but significantly increased risk of lymphoma in adults with inflammatory bowel disease (IBD), especially in patients treated with thiopurines. No data was available from Eastern Europe. The aim of this study was to analyze the incidence of lymphomas as related to drug exposure, in a population-based Veszprem province database, which included incident cases diagnosed between January 1, 1977 and December 31, 2008. Methods: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 36.5 years; CD: 506, age at diagnosis: 28.5.5 years). Both in-and outpatient records were collected and comprehensively reviewed. The rate of lymphoma was calculated as patient-years of exposure per medication class, of medications utilized in IBD. A v a i l a b l e o n l i n e a t w w w . s c i e n c e d i r e c t . c o mJournal of Crohn's and Colitis (2013) 7, 385-391 Downloaded from https://academic.oup.com/ecco-jcc/article-abstract/7/5/385/377770 by guest on 07 June 2019Results: Of the 1420 patients, we identified three patients who developed lymphoma (one CLL, two low-grade B-cell NHL including one rectal case), during 19,293 patient-years of follow-up (median follow-up: 13 years). All three patients were male. None had received azathioprine or biologicals. The absolute incidence rate of lymphoma was 1.55 per 10,000 patient-years, with 3 cases observed vs. 2.18 expected, with a standardized incidence ratio (SIR) of 1.37 (95% confidence interval . No cases have been exposed to either azathioprine or biologicals. Conclusions: The overall risk of lymphoma in IBD was not increased; only three cases were seen in this population-based incident cohort over a 30-year period. An association with thiopurine exposure was not found.

Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti–Tumor Necrosis Factor Therapy for Crohn’s Disease: A Meta-analysis of Placebo-controlled Trials

“…adalimumab and certolizumab) and more recent data 20,21 suggests that there may be legitimate safety concerns related to immunomodulator use to consider before using combination therapy. 22 Subjects in SONIC were naive to both IM and anti-TNF therapy and most had a short disease duration.…”

EBV-associated colonic B-cell lymphoma following treatment with infliximab for IBD: a new problem?

“…Most population-based studies indicate a risk similar to that of the general population, with one recent study giving an absolute incidence rate of 1.55/10 000 patient-years and a standardised incidence ratio (SIR) of 1.37 (95% CI 0.44 to 4.26) 1. Furthermore, the severity of the disease is not thought to confer an increased risk, unlike in rheumatoid arthritis patients where chronic active inflammation is associated with a higher incidence of lymphoma 5…”

Recent Advances Using Immunomodulators for Inflammatory Bowel Disease

“…90 Recent population cohort studies have assessed the risk of lymphoma in patients with IBD. 88,[91][92][93][94][95][96] A nationwide Dutch study did not suggest any overall significantly increased risk for lymphoma in IBD patients, 96 whereas 3 French studies and a large nested, controlled study using the United Kingdom General Practice Research Database demonstrated an increased risk of developing lymphoproliferative disorders among patients treated with thiopurines for IBD. [92][93][94][95] Whether this association is causal or it is the inflammation that thiopurines are used to diminish that actually causes the lymphoproliferative disorders has not yet been determined, but the available data add further weight to the argument that the benefits of thiopurines used in IBD greatly outweigh their risks.…”

“…Recent population cohort studies have assessed the risk of lymphoma in patients with IBD . A nationwide Dutch study did not suggest any overall significantly increased risk for lymphoma in IBD patients, whereas 3 French studies and a large nested, controlled study using the United Kingdom General Practice Research Database demonstrated an increased risk of developing lymphoproliferative disorders among patients treated with thiopurines for IBD .…”