Risk of malignant lymphomas in patients with inflammatory bowel disease: a population-based cohort study

Objective To estimate the risk of non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL) in patients with inflammatory bowel disease (IBD). Design We undertook a two-country population cohort study with all patients diagnosed with IBD in Norway and Sweden from 1987 and 1993 through 2015 and 2016, respectively, and analysed the risk of NHL and HL. In Sweden, we also analysed prescriptions of thiopurines and anti-tumour necrosis factor (TNF)-α therapy from 2005. We calculated standardised incidence ratios (SIRs) with 95% CIs using the general populations as reference. Results Among 131 492 patients with IBD with a medium follow-up of 9.6 years, we identified 369 cases of NHL and 44 cases of HL. The SIR of NHL was 1.3 (95% CI 1.1 to 1.5) in ulcerative colitis and 1.4 (95% CI 1.2 to 1.7) in Crohn’s disease. We found no compelling heterogeneity in analyses stratified by patient characteristics. We found a similar pattern and magnitude of excess risks for HL. At 10 years, cumulative incidence was 0.26% (95% CI 0.23% to 0.30%) and 0.06% (95% CI 0.04% to 0.08%) for NHL and HL, respectively. Higher excess risks were found among patients with NHL with concomitant primary sclerosing cholangitis (SIR 3.4; 95% CI 2.1 to 5.2) and in those prescribed thiopurines alone (SIR 2.8; 95% CI 1.4 to 5.7) or with anti-TNF-α agents (SIR 5.7; 95% CI 2.7 to 11.9). Conclusion Patients with IBD have a statistically significant increased risk of malignant lymphomas compared with the general population, but the absolute risk remains low.


Table of Contents
Yes 17,1 (10,3 to 28,3) 15/12,8 1,2 (0,7 to 1,9) 53,3 (40,5 to 70,2) 51/24,0 2,1 (1,6 to 2,8) IR, incidence rate, per 100 000 person-years; CI, confidence interval; O, observed number of cases; E, expected number of cases; SIR, standardized incidence ratio.# All patients were at risk from one year after IBD diagnosis; a Patients diagnosed before 2002 could represent a mix of prevalent and incident patients with IBD, as outpatient data were gradually included in hospital databases and the Swedish national patient register; b Definitions and diagnostic codes were used according to the Montreal classifications using ICD9 and ICD10 in Norwegian data and using ICD-10 in Swedish data, representing maximum disease involvement during followup, see Table S2 for details; c Patients with primary sclerosing cholangitis contributed person-time to the non-PSC group until the date of PSC diagnosis; d Bowel surgeries included colectomy, small bowel resection, rectal resection, and colon resection during followup.See Table S3 for definitions.
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)   3,5 (1,8 to 7,0) IR, incidence rate, per 100 000 person-years; CI, confidence interval; O, observed number of cases; E, expected number of cases; SIR, standardized incidence ratio.# All patients were at risk from one year after IBD diagnosis; a Patients diagnosed before 2002 could represent a mix of prevalent and incident patients with IBD, as outpatient data were gradually included in hospital databases and the Swedish national patient register; b Definitions and diagnostic codes were used according to the Montreal classifications using ICD9 and ICD10 in Norwegian data and using ICD-10 in Swedish data, representing maximum disease involvement during followup, see Table S2 for details; c Patients with primary sclerosing cholangitis contributed person-time to the non-PSC group until the date of PSC diagnosis; d Bowel surgeries included colectomy, small bowel resection, rectal resection, and colon resection during followup.See Table S3 for definitions.
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)

Fig. S2 .
Fig. S2.Design diagram of analyses on pharmacotherapy in the Swedish cohort.Diagram inspired by the work of Schneeweiss et al., 1 made using template available at https://presc.sdu.dk/repeat-diagrams/

Fig. S1. Overview of cohort members included in analysis.
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance placed on this supplemental material which has been supplied by the author(s) BMJ Open Gastro doi: 10.1136/bmjgast-2022-001037 :e001037.10 2024; BMJ Open Gastro , et al.Yu J

Table S1 . ICD codes used to define patients with inflammatory bowel disease (IBD) from national patient registry and hospital databases.
Unclassified, 1st code IBD-U, 2nd code IBD-U, or any combination of codes for UC, CD, and IBD-U.ICD-9 was implemented in Sweden in 1987, and in Norway in 1986.ICD-10 was implemented inSweden 1997,  and in Norway in 1999.

Table S2 . Definitions and diagnostic codes used to define ulcerative colitis (UC) and Crohn's disease (CD) according to the Montreal classification.
Norway in 1999.All codes were captured in the Swedish National Patient Register and Norwegian hospital databases.BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)

Table S5B .
ICD-O-2 and SNOMED codes for leukemia and lymphomas in Sweden.