Immunosuppressives Unlikely to Raise Cancer Risk in IBD Patients With Prior Cancer

Carolyn Crist

In patients with inflammatory bowel disease (IBD) and a history of cancer, immunosuppressive therapies don't appear to increase the risk for incident cancer, according to an interim analysis of the SAPPHIRE registry.

Although immunosuppressive therapies were associated with numerically higher adjusted hazard ratios for incident cancer, the association wasn't considered statistically significant.

"Patients with IBD who have a history of cancer are typically excluded from clinical trials of new IBD drugs for fear of reactivating their cancer. Therefore, the data on how much risk for subsequent cancer is posed by taking IBD medications is limited," said lead author Steven Itzkowitz, MD, professor of medicine, oncological sciences, and medical education at the Icahn School of Medicine at Mount Sinai, New York City.

photo of Steven Itzkowitz, MD
Steven Itzkowitz, MD

"Many physicians and patients have been reluctant to administer potentially very helpful IBD medications to those who have a history of cancer," added Itzkowitz, who chairs the American Cancer Society National Colorectal Cancer Roundtable. "Understanding the risk of exposure to IBD medications in patients with a history of cancer offers providers and patients with data to make informed decisions about their IBD care."

The study was published online in Clinical Gastroenterology and Hepatology.

Analyzing the SAPPHIRE Registry

The SAPPHIRE registry is a prospective study of the safety of immunosuppression in patients with IBD with a history of cancer before enrollment. Started in 2016, the registry is affiliated with the New York Crohn's and Colitis Organization. It follows patients annually to check for the development of incident malignancy and tracks the initial cancer type and IBD medications taken.

In the interim analysis, Itzkowitz and colleagues looked at the development of incident cancer (recurrent or new). The researchers excluded patients receiving active cancer treatment (chemotherapy or radiation) or who had more than one cancer before enrollment.

Patients were categorized on the basis of medication type, such as tumor necrosis factor inhibitor (anti-TNF), antimetabolite, anti-integrin, anti-interleukin (IL)-12/23, anti-IL-23, Janus kinase inhibitor, or sphingosine 1-phosphate receptor. Those only exposed to mesalamine or steroids weren't considered to be exposed to the immunosuppressive drugs of interest.

Of the 305 patients, 47% were men, 88% White, and 61% never smokers. The median age at IBD diagnosis was 32 years, and the median age at cancer diagnosis was 52 years.

Index cancers were solid organ (46%), dermatologic (32%), gastrointestinal (13%), and hematologic (9%). Of index cancers with known stage information, 33% were stage I.

During a median follow-up of 4.8 years, 210 patients (69%) were exposed to immunosuppressive therapies and 36 (17%) of them developed incident cancers. Of the 95 patients who were not exposed to immunosuppressive therapies, 10 (11%) developed incident cancer.

Among all 46 incident cancer cases, 25 were new cancers and 21 recurrent. The 36 patients exposed to immunosuppressive therapy who developed cancer during follow-up constituted 78% of the incident cancer cases (21 new and 15 recurrent).

In an unadjusted analysis, the crude rate of incident cancer in unexposed patients was 2.58 per 100 person-years vs 4.78 per 100 person-years among patients exposed to immunosuppression (relative risk, 1.85).

However, in a proportional hazards model adjusting for sex, smoking history, age, stage at index cancer, and nonmelanoma skin cancer, no significant association was found between immunosuppression therapy exposure and incident cancer (adjusted hazard ratio, 1.41). There also wasn't a significant association found between immunosuppression and any major drug class.

"We were not surprised by the findings because they seem to confirm findings from retrospective studies," Itzkowitz said. "We are, however, gratified to see that the various agents that affect different arms of the immune system seem to be relatively safe in patients with IBD who have a history of cancer, but it must be understood that we need more follow-up and more experience with the newer medications before we can be more fully reassured."

A Step Forward

Gastroenterologists increasingly must confront the challenge of deciding about immunosuppressive agents for patients with prior cancer. As there are more immunosuppressive therapies, we are using them earlier in the course of IBD treatment, and patients are getting older, said Ashwin Ananthakrishnan, MBBS, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, Boston.

photo of Ashwin Ananthakrishnan, MBBS
Ashwin Ananthakrishnan, MBBS

Ananthakrishnan, who wasn't involved with this study, has researched the association of immunosuppressive therapies with the risk for cancer recurrence among patients with IBD. He and colleagues found that neither vedolizumab nor anti-TNF agents were associated with an increased risk for new or recurrent cancer.

"This [SAPPHIRE interim analysis] was a very important study because it was one of the first prospective studies to examine this question," he said. "Multiple studies have looked at it before but have all been retrospective, which raises the potential for bias."

Itzkowitz and colleagues highlighted many of these retrospective studies and the SAPPHIRE findings in a May 2024 American Gastroenterological Association Institute Clinical Practice Update Commentary. Although patients with prior cancers may not face an increased risk, those with active or recent cancer likely do, they wrote. While the authors noted the limited data on IBD therapies in patients with active cancer, they offered guidance on specific therapies and malignancies. In some cases, for instance, thiopurines and anti-TNF agents should be stopped during cancer treatment, and alternative therapies should be considered.

SAPPHIRE researchers plan to continue to follow the existing patients and enroll new patients, particularly as new IBD medications are introduced into clinical practice, Itzkowitz said. The research team is also considering studies that investigate patients with IBD who are undergoing active cancer treatment.

Physicians "need more data on the safety of newer agents and newer mechanisms," Ananthakrishnan said. "And we particularly need to examine outcomes in those who initiated treatment closer to cancer diagnosis."

The study received support from the Crohn's and Colitis Foundation Clinical Research Alliance and Senior Research Award, The Chemotherapy Foundation, the New York Crohn's and Colitis Organization, and the Helmsley Charitable Trust. Several authors reported grants, consultancy fees, and advisory roles for numerous pharmaceutical companies. Ananthakrishnan reported no relevant disclosures.

Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape Medical News, MDedge, and WebMD.

 

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