Introduction:
Oral small molecules (OSM) have demonstrated effectiveness in treating IBD. Certain studies have associated certain OSM with an increased cancer risk. We aimed to assess the cancer risk in IBD patients treated with OSM.

Methods:
We utilized the TriNetX multi-institutional database to assess cancer risk in adult IBD patients treated with OSM (Tofacitinib, Upadacitinib, or Ozanimod). These individuals were compared to all adult IBD patients not receiving OSM. Additionally, we compared the cancer risk in IBD patients who received OSM to those on biologics (Infliximab, Adalimumab, Golimumab, Certolizumab, Vedolizumab, Natalizumab, or Ustekinumab). Subgroup analysis was conducted of older IBD patients (age> 50) who received JAKi (Tofacitinib or Upadacitinib). We performed 1:1 propensity score matching for age, race, sex, smoking, alcohol use, IBD-related medications, family history of cancer, PSC, HBV, HCV, HPV, and other comorbidities. We assessed the composite of all malignancies at various time intervals following OSM prescription. Patients with outcomes prior to prescription were excluded from the study.

Results:
When compared to all IBD patients not on OSM, there were no significant differences in the composite outcome of all cancers at 1 year (aOR 1.06, 95% CI 0.74–1.51), 2 years (aOR 1.07, 95% CI 0.82–1.41), 3 years (aOR 1.10, 95% CI 0.86–1.40), and 4 years (aOR 1.00, 95% CI 0.80–1.24) following OSM prescription. In a subgroup analysis of older IBD patients who received JAKi, there was no increased risk of cancers at 1 year (aOR 1.01, 95% CI 0.65,1.58), 2 years (aOR 1.03, 95% CI 0.73,1.43), 3 years (aOR 1.04, 95% CI 0.77,1.41), and 4 years (aOR 1.00, 95% CI 0.75,1.32) following JAKi prescription, compared to older IBD patient not on JAKi. When compared to all IBD patients on biologics, no significant differences were observed in the composite outcome of all cancers at 1 year (aOR 0.89, 95% CI 0.63–1.24), 2 years (aOR 0.99, 95% CI 0.77–1.29), 3 years (aOR 0.92, 95% CI 0.73–1.16), and 4 years (aOR 0.89, 95% CI 0.72–1.11) following OSM prescription.

Conclusion:
OSM do not increase the risk of malignancies. Importantly, there was not an increase in malignancies in older IBD patients treated with OSM. While further studies and longer follow up periods are needed to validate these findings, our results provide reassurance regarding the safety of OSM in IBD.

Faris Hammad

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