From the Journals

Do biologics protect against cancer progression in IBD?



Treatment with a biologic agent was associated with a lower risk of advanced inflammatory bowel disease (IBD)–associated cancer in patients with ulcerative colitis (UC) but not Crohn’s disease (CD) in an observational study conducted in Japan.

IBD-associated intestinal cancer is thought to be caused by chronic inflammation of the intestinal mucosa, and controlling inflammation is thought to be effective in reducing cancer risk.

It’s generally considered that biologics do not change the risk of cancer, and whether they lower the risk remains unclear, write Ryo Seishima, MD, PhD, with Keio University in Tokyo, and colleagues. However, few studies have focused on cancer progression, namely, the risk of advanced-stage cancer.

To investigate, researchers reviewed the medical records of 828 patients with UC and 214 with CD who were diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020.

Therapeutic agents taken within 1 year before neoplasia diagnosis were classified into three types: biologics (infliximab, vedolizumab, golimumab, and adalimumab), 5-aminosalicylic acid (5-ASA), and immunomodulators.

The primary endpoint was the pathologic cancer stage at the time of diagnosis. Early-stage cancer was defined as either dysplasia or pathologic stage 0/I cancer, and advanced-stage cancer was defined as pathologic stage II/III/IV cancer.

Advanced-stage cancer was found in 297 patients (35.9%) with UC and 159 patients (74.3%) with CD.

The researchers say the higher percentage of advanced cancer in patients with CD rather than in patients with UC may suggest that regular surveillance was not effective for patients with CD or that physicians were less adherent to surveillance intervals. This question merits further study, they suggest.

None of the drug types were significantly associated with cancer stage in the CD cohort, they report.

Benefits seen in UC

In the UC cohort, advanced-stage cancer (vs. early-stage) was significantly associated with less use of biologics (2% vs. 7.7%; P < .001), 5-ASA (75.4% vs. 87.6%; P < .001), and immunomodulators (11.8% vs. 22.4%; P < .001). Steroid use was also significantly lower in the advanced-stage cancer group (26.3% vs. 33.3%; P = .035).

In multivariate analysis that was adjusted for age, diagnosis year, regular surveillance, and histologic type in UC, biologics (odds ratio, 0.11; P < .001) and 5-ASA (OR, 0.63; P = .041) were significantly associated with a lower risk of advanced-stage cancer.

The study was published online in The American Journal of Gastroenterology.

“These results indicate that biologics and 5-ASA are drugs that are potentially associated with a lower risk of advanced cancer in patients with UC but not with CD,” Dr. Seishima and colleagues say.

They also suggest that the mechanism of cancer progression in UC and CD may differ and needs to be investigated further.

Reassuring data with caveats

The study is “interesting and reassuring, but there are a lot of limitations with the study design,” said Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who was not involved in the research.

Dr. Ashwin N. Ananthakrishnan, associate professor of medicine at Massachusetts General Hospital in Boston

Dr. Ashwin N. Ananthakrishnan

“By focusing only on those who have been diagnosed with cancer, one cannot actually conclude what the risk of cancer is and if these medications reduce the risk of colon cancer, which is a far more important and interesting question,” he said.

Patients undergoing treatment with biologics likely receive closer follow-up, so in these patients, cancers are less likely to be diagnosed at an advanced stage, said Dr. Ananthakrishnan. For that reason, the study can’t clearly establish the degree to which the effect was from medication or surveillance, he added.

As for whether biologics affect the overall risk of cancer development, the study doesn’t change “current thinking that biologics are safe in this setting,” he added.

Erin Forster, MD, MPH, with the Medical University of South Carolina, Charleston, also weighed in on medication safety.

“Prior research has shown that the risk of uncontrolled inflammation outweighs the risk of our current medications,” Dr. Forster, who was not involved in the research, said in an interview.

The study had no specific funding. Dr. Seishima, Dr. Ananthakrishnan, and Dr. Forster have disclosed no relevant financial relationships.

A version of this article first appeared on

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