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Increasing Risk of Lymphoma Over Time in Crohn's Disease but Not in Ulcerative Colitis : A Scandinavian Cohort Study

Olén, Ola ; Smedby, Karin E. ; Erichsen, Rune ; Pedersen, Lars ; Halfvarson, Jonas ; Hallqvist-Everhov, Åsa ; Bryder, Nicklas ; Askling, Johan ; Ekbom, Anders and Sachs, Michael C. , et al. (2023) In Clinical Gastroenterology and Hepatology 21(12). p.3132-3142
Abstract

Background & Aims: Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD. Methods: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation. Results: From 1969 to 2019, 258 patients with Crohn's disease... (More)

Background & Aims: Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD. Methods: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation. Results: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16–1.50) and UC (HR, 1.09; 95% CI, 1.00–1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02–0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naïve to such drugs. Conclusions: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.

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Olsson, Malin ; Bengtsson, Jonas ; Andersson, Marie ; Björk, Jan and LU
author collaboration
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Crohn's Disease, Elderly IBD, Epidemiology, IBD, IBD Unclassified, IBDU, Inflammatory Bowel Disease, Lymphoid Neoplasm, Lymphoma, Pediatric IBD, Population-Based, Ulcerative Colitis
in
Clinical Gastroenterology and Hepatology
volume
21
issue
12
pages
3132 - 3142
publisher
Elsevier
external identifiers
  • pmid:37061104
  • scopus:85163864612
ISSN
1542-3565
DOI
10.1016/j.cgh.2023.04.001
language
English
LU publication?
no
id
791e098d-b05e-4cce-be17-d350b0861a8b
date added to LUP
2023-08-03 14:44:21
date last changed
2024-04-20 00:06:24
@article{791e098d-b05e-4cce-be17-d350b0861a8b,
  abstract     = {{<p>Background &amp; Aims: Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD. Methods: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation. Results: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16–1.50) and UC (HR, 1.09; 95% CI, 1.00–1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02–0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naïve to such drugs. Conclusions: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.</p>}},
  author       = {{Olén, Ola and Smedby, Karin E. and Erichsen, Rune and Pedersen, Lars and Halfvarson, Jonas and Hallqvist-Everhov, Åsa and Bryder, Nicklas and Askling, Johan and Ekbom, Anders and Sachs, Michael C. and Sørensen, Henrik Toft and Ludvigsson, Jonas F.}},
  issn         = {{1542-3565}},
  keywords     = {{Crohn's Disease; Elderly IBD; Epidemiology; IBD; IBD Unclassified; IBDU; Inflammatory Bowel Disease; Lymphoid Neoplasm; Lymphoma; Pediatric IBD; Population-Based; Ulcerative Colitis}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{3132--3142}},
  publisher    = {{Elsevier}},
  series       = {{Clinical Gastroenterology and Hepatology}},
  title        = {{Increasing Risk of Lymphoma Over Time in Crohn's Disease but Not in Ulcerative Colitis : A Scandinavian Cohort Study}},
  url          = {{http://dx.doi.org/10.1016/j.cgh.2023.04.001}},
  doi          = {{10.1016/j.cgh.2023.04.001}},
  volume       = {{21}},
  year         = {{2023}},
}