Inflammatory bowel disease, cancer and medication: Cancer risk in the Dutch population‐based IBDSL cohort

Abstract

The management of inflammatory bowel disease (IBD) has changed since the mid-1990s (e.g., use of thiopurines/anti-TNFα agents, improved surveillance programs), possibly affecting cancer risk. To establish current cancer risk in IBD, updates are warranted from cohorts covering this time span, and detailed enough to study associations with phenotype and medication. We studied intestinal-, extra-intestinal- and overall cancer risk in the Dutch population-based IBDSL cohort. In total, 1,157 Crohn's disease (CD) and 1,644 ulcerative colitis (UC) patients were diagnosed between 1991 and 2011, and followed until 2013. Standardized incidence ratios (SIRs) were calculated for CD and UC separately, as well as for gender-, phenotype-, disease duration-, diagnosis era- and medication groups. We found an increased risk for colorectal cancer in CD patients with colon involvement (SIR 2.97; 95% CI 1.08-6.46), but not in the total CD or UC population. In addition, CD patients were at increased risk for hematologic- (2.41; 1.04-4.76), overall skin- (1.55; 1.06-2.19), skin squamous cell- (SCC; 3.83; 1.83-7.04) and overall cancer (1.28; 1.01-1.60), whereas UC patients had no increased risk for extra-intestinal- and overall cancer. Finally, in a medication analysis on CD and UC together, long-term immunosuppression exposure (>12 months) was associated with an increased risk for hematologic cancer, non-Hodgkin lymphoma, SCC and overall cancer, and this increase was mainly attributed to thiopurines. IBD patients with long-term immunosuppression exposure can be considered as having a higher cancer risk, and our data support the advice in recent IBD guidelines to consider skin cancer screening in these patients.

The aetiology of B‐cell lymphoid malignancies with a focus on chronic inflammation and infections

“…with tumour necrosis factor antagonists, often given for autoimmune conditions, may cause an increase in lymphoma incidence [55], although it cannot be entirely excluded either. In contrast, in Chron's disease, evidence is accumulating of a link between thiopurine medication and NHL risk [48].…”

“…Disorders most consistently associated with increased risks include Sjogren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, autoimmune thyroiditis, coeliac disease and dermatitis herpetiformis [45,46]. Also, chronic inflammatory conditions such as Crohn's disease [47,48] and psoriasis [49] have often but not always been linked to increased lymphoma risks. An array of other immune-mediated disorders such as haemolytic anaemia, myositis and idiopathic trombocyopenic purpura have also been linked with lymphoma risk [45], although risks have been observed to peak around the time of diagnosis of the lymphoma, implying that these disorders may primarily occur as paramalignant autoimmune phenomena.…”

Risk of skin cancers in thiopurines‐treated and thiopurines‐untreated patients with inflammatory bowel disease: A systematic review and meta‐analysis

“…Effect of thiopurines on the risk of nonmelanoma skin cancer. Eleven studies (two nested case-controls 26,27 and nine cohorts 7,8,18,[20][21][22][23][24]28 ) evaluated the association between thiopurines use and NMSC risk. Meta-analysis of nine cohort studies showed that thiopurines use increases the risk of NMSC (random effects: RR = 2.15, 95% CI 1.40-3.30, P < 0.001, Q = 21.43, P for heterogeneity 0.006, I 2 = 62.7%).…”

“…Effect of thiopurines on the risk of melanoma skin cancer. Four studies (two nested case-controls 26,27 and two cohorts 18,28 ) reported the risk of MSC in IBD patients after exposure to thiopurines. The association of thiopurines use with MSC was not statistically significant in either cohort studies (fixed effects: RR = 1.30, 95% CI 0.57-2.99, P = 0.531, Q = 1.18, P for Figure 2 Forest plots evaluating skin cancer risk in thiopurines-exposed versus thiopurines-unexposed groups.…”

Vedolizumab use is not associated with increased malignancy incidence: GEMINI LTS study results and post‐marketing data

“…Notably, infliximab carries a “black box” warning regarding malignancies . Furthermore, a population‐based cohort study found that long‐term (>12 months) immunosuppression was associated with increased risk of haematologic cancer, non‐Hodgkin lymphoma, squamous cell skin cancer and overall cancer, primarily attributable to thiopurine use . In contrast, a registry‐based cohort study found no significant increase in cancer risk for patients with IBD receiving anti‐TNFα therapy vs no anti‐TNFα therapy over a median follow‐up of 3.7 years …”