Reduced Risk of Inflammatory Bowel Disease-associated Colorectal Neoplasia with Use of Thiopurines: a Systematic Review and Meta-analysis

Zhu, Zhehui; Mei, Zubing; Guo, Yao; Wang, Guanghui; Wu, Tingyu; Cui, Ximao; Huang, Zhenyu; Zhu, Yue; Wen, Dongpeng; Song, Jinglve; He, Haiqi; Xu, Weimin; Cui, Long; Liu, Chenying

doi:10.1093/ecco-jcc/jjy006

Cited by 47 publications

(44 citation statements)

References 83 publications

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“…Although the focus of this study was on the incidence and prevalence of inflammatory bowel disease and the risk of mortality and colorectal cancer in these populations, a significant limitation is in identification of inflammatory bowel disease phenotype. It has previously been shown that disease severity, extent and comorbid primary sclerosing cholangitis are significant factors in the risk of colorectal cancer in inflammatory bowel disease 6,50 . This study has considered all Crohn's disease and all ulcerative colitis as single diseases and the paucity of data in THIN regarding inflammatory bowel disease phenotypic subtypes would not permit a more in‐depth analysis of how these factors affect colorectal cancer and mortality risk.…”

Section: Discussionmentioning

confidence: 99%

Changing patterns in the epidemiology and outcomes of inflammatory bowel disease in the United Kingdom: 2000‐2018

King

Reulen

Thomas

et al. 2020

Aliment Pharmacol Ther

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Background: Data regarding incidence, prevalence and long-term outcomes of inflammatory bowel diseases in the UK are limited or outdated. Aims:To investigate incidence and prevalence of Crohn's disease and ulcerative colitis and risk of colorectal cancer and all-cause mortality in these diseases.Methods: Inflammatory bowel disease cases between 2000 and 2018 were identified from a national primary care database. Inflammatory bowel disease prevalence was forecast until 2025. The association between inflammatory bowel disease and colorectal cancer and all-cause mortality was investigated using age/sex-matched retrospective cohort studies. Hazard ratios were adjusted for age, sex, deprivation, comorbidity, smoking status and body mass index.Results: Ulcerative colitis prevalence increased from 390 to 570 per 100 000 population from 2000 to 2017. Prevalence of Crohn's disease increased from 220 to 400 per 100 000. In 2017 male Crohn's disease prevalence was 0.35% (95% confidence interval 0.34-0.36); female prevalence was 0.44% (0.43-0.45). Prevalence of inflammatory bowel disease is predicted to be 1.1% by 2025. Incidence of ulcerative colitis and Crohn's disease was 23.2 (22.8-23.6) and 14.3 (14.0-14.7) per 100 000 person-years respectively. Subjects with ulcerative colitis were more likely to develop colorectal cancer than controls (adjusted Hazard Ratio 1.40 [1.23-1.59]). Colorectal cancer rates remained stable in inflammatory bowel diseases over time. Ulcerative colitis and Crohn's disease were associated with increased risk of all-cause mortality (1.17 [1.14-1.21] and 1.42 [1.36-1.48] respectively). Conclusions: The UK prevalence of inflammatory bowel disease is greater than previous reports suggest and we predict an 11% increase in prevalence by the year 2025. Mortality risk in inflammatory bowel disease and colorectal cancer risk in ulcerative colitis are increased compared to matched controls. | 923 KING et al. Studies reporting increased mortality riskStudies reporting decrease/equivalent mortality risk Crohn's Disease Ulcerative Colitis Crohn's Disease Ulcerative ColitisAbbreviations: HR, hazard ratio; SMR, standardised mortality ratio.

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Section: Discussionmentioning

confidence: 99%

Changing patterns in the epidemiology and outcomes of inflammatory bowel disease in the United Kingdom: 2000‐2018

King

Reulen

Thomas

et al. 2020

Aliment Pharmacol Ther

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“…A 2018 meta-analysis by Zhu et al reinforced the antineoplastic activity of thiopurine-based immunomodulators, with an odds ratio of 0.51 for HGD and 0.55 for CRC. 15 Rates of immunomodulator and biologic use in CD were higher, although nearly half (47% (n = 8, CI 26-69%) only received a biologic for 6 months or less prior to the neoplasia diagnosis. While there are few long-term data regarding CRC risk reduction with anti-TNF agents, a 2011 Dutch case-control study of 173 cases of IBD-associated CRC found a significant reduction in CRC risk with the use of infliximab, with an odds ratio of 0.09.…”

Section: Discussionmentioning

confidence: 92%

“…[1][2][3][4] The incidence, although variably reported, is believed to be as high as 18% in ulcerative colitis (UC) and 8.3% in Crohn's disease (CD) after a disease duration of 30 years. 5,6 The median age of onset of CRC in IBD is as young as 43 years, up to [15][16][17][18][19][20] years earlier than that of sporadic CRC. 5 The prognosis is poor, with an overall 5-year survival of 33-55% for UC-associated and 18-46% for CD-associated CRC.…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal neoplasia in patients with inflammatory bowel disease: Opportunities to enhance preventative strategies

et al. 2019

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Background and AimsGastrointestinal (GI) adenocarcinoma, especially colorectal cancer (CRC), is a devastating complication of inflammatory bowel disease (IBD). We sought to examine the role of chronic inflammation and other possible predictors of the development of CRC, as well as assess as yet unexamined factors such as psychological comorbidity and engagement in care.MethodsThis study included all patients involved in a tertiary hospital IBD service diagnosed with CRC between 2007 and 2017. Reports from histological specimens were assessed, and all those with adenocarcinoma, high‐grade dysplasia (HGD), or multifocal low‐grade dysplasia (LGD) originating within IBD‐affected mucosa were included in the study.ResultsA total of 32 patients were included in the study (17 with adenocarcinoma and 15 with HGD/multifocal LGD). The majority had a duration of disease >20 years. Eleven patients (34%, CI 20–52%) had previous disease‐related surgery, and 16 (50%, CI 34–66%) had multiple previous disease‐related admissions. Thirteen patients (62%, CI 41–79%) had >50% of CRP results higher than 8 mg/L. Psychiatric comorbidities were common, with 19 patients (59%, CI 42–74%) having a psychiatric comorbidity or poor engagement in treatment.ConclusionIn this cohort, we have highlighted poor engagement, hesitation to up‐titrate therapy when indicated, and psychological comorbidities as likely contributors to poor disease control and development of GI adenocarcinoma. Based on our data, these easily identifiable clinical care factors should not be overlooked when addressing IBD‐related GI malignancy prevention. Additional research is required to assess a direct causal relationship, but this study would support the incorporation of psychology services into IBD clinics.

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“…The first benefit of 5‐ASA appears to relate to control of colonic inflammation, and therefore as expected is not specific to 5‐ASA. A recent systematic review and meta‐analysis of 27 studies involving 95 937 patients with IBD demonstrated that thiopurine use was associated with a reduced risk of both high‐grade dysplasia and CRC, particularly among those with a longer disease duration, 65 although the risk reduction appeared limited to those with UC in a separate meta‐analysis 66 . The second potential benefit relates to the postulated direct chemopreventive effects of 5‐ASA, with studies suggesting a range of relevant biological mechanisms including cell checkpoint activation, 67 improvement of DNA replication fidelity, 68 scavenging of reactive oxygen and nitrogen species 69 and interference with Wnt/beta‐catenin signalling 70 .…”

Section: The Role Of 5‐asa In Crc Prevention—a Key Consideration?mentioning

confidence: 99%

Review article: withdrawal of 5‐aminosalicylates in inflammatory bowel disease

Chapman

Gomes

Louis

et al. 2020

Aliment Pharmacol Ther

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Summary Background 5‐aminosalicylates (5‐ASA) are widely used in inflammatory bowel disease (IBD), but emerging evidence suggests that they may be safely withdrawn in significant subsets of patients. This is important to address: 5‐ASA therapy accounts for up to 25% of total healthcare costs in ulcerative colitis (UC), while almost a third of patients with Crohn's disease (CD) receive long‐term 5‐ASA despite no clear evidence of benefit. Further, rationalising medication burden may improve overall adherence and outcome. Aims To summarise the rationale for 5‐ASA withdrawal, review the current evidence in both UC and CD and consider the data surrounding colorectal cancer (CRC) prevention, guiding an evidence‐based withdrawal strategy. Methods PubMed was searched to identify relevant studies. Only papers published in English were reviewed, with priority given to randomised clinical trials and meta‐analyses. Results For patients with UC, consideration of 5‐ASA withdrawal should be made on a case‐by‐case basis, but it appears safest for those in deep remission without any of the following risk factors: younger age (<40 years), remission for less than 2 years, a history of multiple flares, extensive disease. 5‐ASA withdrawal should also be considered in patients with UC escalated to biologic therapy who have achieved remission and in all patients with CD. Although 5‐ASA therapy may have chemopreventive benefits for CRC, the cost‐benefit ratio appears significant, and this indication is not justified by evidence in those who have achieved remission and are continuing therapy with other agents, or in those in sustained remission without a history of extensive disease. Conclusions Although the majority of patients with IBD receive 5‐ASA during their disease course, safe withdrawal appears possible in many, with important implications for both health economics and patient experience. A number of unanswered questions, however, remain.

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Reduced Risk of Inflammatory Bowel Disease-associated Colorectal Neoplasia with Use of Thiopurines: a Systematic Review and Meta-analysis

Abstract: This study demonstrated that thiopurine use was associated with a reduced risk of colorectal neoplasia, advanced neoplasia and CRC in IBD patients, especially those with long disease duration [> 8 years].

Cited by 47 publications

References 83 publications

Changing patterns in the epidemiology and outcomes of inflammatory bowel disease in the United Kingdom: 2000‐2018

Changing patterns in the epidemiology and outcomes of inflammatory bowel disease in the United Kingdom: 2000‐2018

Gastrointestinal neoplasia in patients with inflammatory bowel disease: Opportunities to enhance preventative strategies

Review article: withdrawal of 5‐aminosalicylates in inflammatory bowel disease

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