Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study

Abstract

INTRODUCTION:The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set.METHODS:The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC.RESULTS:In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [−] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034–0.356], P < 0.001).DISCUSSION:Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

Treat-to-Target and Regular Surveillance of Inflammatory Bowel Disease Are Associated with Low Incidence and Early-Stage Detection of Malignancies: A Retrospective Cohort Study

“…We believe that, altogether, these improvements are responsible for the reduction in excess cancer. Consistent with the broader trend of diminished CRC risk, published data on cancer stage at the time of diagnosis, although indirect, point to a reduction in advanced-stage cancer diagnosis in more recent cohorts [35]. In line with this, our study found that only 2 out of 28 malignancies included in some form of surveillance were diagnosed at advanced (III-IV) stage.…”

“…The safety profile of these treatments is now well established and their risk of malignancy reassuring. Interestingly, a recent Japanese nationwide study including over a thousand IBD-associated cancers found that use of biologics was associated with earlier-stage, rather than advanced-stage, cancer in UC patients [35]. Although the limited sample size of our cohort impeded a formal analysis, it is worth noting that three out of four patients who developed a hematologic malignancy were being, or had been, treated with azathioprine, which is known to increase the risk of lymphoproliferative disorders [44][45][46].…”

Histological differentiation between sporadic and colitis‐associated intestinal cancer in a nationwide study: A propensity‐score‐matched analysis

“…The associations between treatment, surveillance colonoscopy, or disease behavior and carcinogenesis or prognosis have been evaluated using the same data set in other sub-analyses. 6,26,27 Second, the diagnoses of sporadic CRC and CAC in patients with IBD were made at individual institutions and not a central institution, and the diagnoses may not have been standardized. A second review of histological findings was not performed.…”

“…Moreover, the prevalence of primary sclerosing cholangitis, which is one of the cancer risks in those with IBD, was not included in this data set. The associations between treatment, surveillance colonoscopy, or disease behavior and carcinogenesis or prognosis have been evaluated using the same data set in other sub‐analyses 6,26,27 . Second, the diagnoses of sporadic CRC and CAC in patients with IBD were made at individual institutions and not a central institution, and the diagnoses may not have been standardized.…”

Anal Cancer in Crohn's Disease: The Need to Optimize Treatment and Improve Surveillance

“…Patients with Crohn's disease (CD) and ulcerative colitis (UC) are more likely to be diagnosed with cancer than the general population (1). Hence, we commend Seishima et al for evaluating the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer (2). Factors deemed to increase IBD-associated dysplasia have been incorporated into endoscopic guidelines to facilitate a risk-based approach to dysplasia surveillance, albeit with a focus tailored moreso toward UC than CD (3).…”