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May 22, 2024/Digestive/Research

Study Finds No Connection Between OSMs and Increased Cancer Rates in IBD Patients

Reassuring results, but patient education is still important

Patient taking medication

New data shows that oral small molecules (OSMs) do not increase the risk of cancer among patients with inflammatory bowel disease (IBD). Results from this Cleveland Clinic-led study, “Oral Small Molecules Are Not Associated with Increased Cancer Rates in IBD Patients,” were recently presented by first author Thabet Qapaja, MD, during the Digestive Disease Week Conference.


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While further studies and longer follow up periods are needed to validate the findings, senior author Miguel Regueiro, MD, and colleagues suggest that their research supports the safety of these drugs in this patient population.

Study details

OSMs have proven effective for the treatment of IBD; however, some studies suggest that certain OSMs are associated with an increased risk of cancer. Dr. Regueiro and his team initiated this study to clarify the cancer risk associated with oral small molecules—both JAK inhibitors and sphingosine 1-phosphate (S1P) receptor modulators.

Using TriNetX, a multi-institutional database, Dr. Regueiro and colleagues assessed cancer risk in adult patients (n = 5,089) treated with oral small molecules — Tofacitinib, Upadacitinib or Ozanimod. These patients were compared to adult IBD patients not receiving OSMs between 2018-2023 (n = 5,089).

“Etrasimod is an oral, once-daily, selective S1P receptor modulator that was recently approved for adults with moderately to severely active ulcerative colitis,” explains Dr. Regueiro. “However, we did not include it in this analysis due to limited clinical data.”

The researchers compared the cancer risk among IBD patients who received oral small molecules to those treated with biologics (Infliximab, Adalimumab, Golimumab, Certolizumab, Vedolizumab, Natalizumab or Ustekinumab). A subgroup analysis of older IBD patients (age > 50) who received JAK inhibitors (Tofacitinib or Upadacitinib) was also conducted.


Dr. Regueiro and team performed 1:1 propensity score matching for age, race, sex, smoking, alcohol use, IBD-related medications, family history of cancer and other comorbidities. During their analysis they assessed the composite of all malignancies at various time intervals following the prescription of an oral small molecule.

When compared to all IBD patients who did not receive OSM treatment, the study authors observed no significant differences in the composite outcome of all cancers at one year (aOR 1.06, 95% CI 0.74–1.51), two years (aOR 1.07, 95% CI 0.82–1.41), three years (aOR 1.10, 95% CI 0.86–1.40), and four years (aOR 1.00, 95% CI 0.80–1.24) following OSM prescription.

The subgroup analysis of older IBD patients who underwent JAK inhibitor treatment showed no increased risk of cancers at one year (aOR 1.01, 95% CI 0.65,1.58), two years (aOR 1.03, 95% CI 0.73,1.43), three years (aOR 1.04, 95% CI 0.77,1.41) and four years (aOR 1.00, 95% CI 0.75,1.32) following JAK inhibitor prescription versus their counterparts who had not received JAK inhibitors.

Additionally, compared to IBD patients on biologics, Dr. Regueiro and colleagues found no significant differences in the composite outcome of all cancers at one year (aOR 0.89, 95% CI 0.63–1.24), two years (aOR 0.99, 95% CI 0.77–1.29), three years (aOR 0.92, 95% CI 0.73–1.16), and four years (aOR 0.89, 95% CI 0.72–1.11) following OSM prescription.

Key takeaways

These findings suggest that the use of oral small molecules does not increase the risk of cancer in patients with inflammatory bowel disease. While Dr. Regueiro acknowledges that database studies like this one do have some limitations, he believes clinicians can take comfort in this data when prescribing these agents.

“We are seeing a good safety signal and shouldn’t limit the use of these effective therapies because of the concern of cancer,” he recommends. “It’s not to say there are no side effects with OSMs, and educating patients on any potential concerns is always important. However, it is reassuring that we are not seeing increased risk of malignancy similar to what was observed in prior rheumatoid arthritis studies.”

This study also opens the door for further research, according to Dr. Regueiro, who notes that the Cleveland Clinic continues to follow and collect data on patients with IBD. “Big picture next steps include taking a closer look at IBD and how inflammation in the body correlates with cancer,” he says. “We are also very interested in precision medicine and how we can personalize care and improve outcomes for patients with inflammatory bowel disease.”


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