Vedolizumab Use Is Not Associated With Increased Malignancy Incidence

GEMINI LTS Study Results and Post-marketing Data

Timothy Card; Ryan Ungaro; Fatima Bhayat; Aimee Blake; Gary Hantsbarger; Simon Travis


Aliment Pharmacol Ther. 2019;51(1):149-157. 

In This Article

Abstract and Introduction


Background: Vedolizumab is a gut-selective antibody to α4β7 integrin approved to treat moderate-to-severe Crohn's disease and ulcerative colitis in adults. Inflammatory bowel disease (IBD) and immunosuppressant use are associated with increased risk of malignancy.

Aim: To analyse the incidence of malignancy with vedolizumab treatment in the GEMINI long-term safety (LTS) study and post-marketing (PM) setting.

Methods: Malignancy data from the LTS study (May 2009 to May 2018), and data from the vedolizumab Global Safety Database (20 May 2014 to 19 May 2018), were identified using Medical Dictionary for Regulatory Activities coding. The number of patients experiencing malignancies in the LTS study (excluding malignancies within 1 year following vedolizumab initiation) was indirectly standardised against the number expected, using age- and sex-specific rates in patients with IBD from Optum's Clinformatics™ Data Mart (CDM) database.

Results: Among 1785 patients with ≥1 year of follow-up post-vedolizumab initiation in the LTS study (total 5670 patient-years), observed numbers of malignancies were similar to those expected compared with CDM data (31 vs 29; ratio of observed to expected events = 1.08; P = 0.71; 95% confidence intervals [CI] 0.73, 1.53). The most common malignancies were renal and bladder (6). PM, 293 patients reported 299 malignancies (including malignancies within 1 year following vedolizumab initiation), in approximately 208 050 patient-years of vedolizumab exposure. Lower gastrointestinal malignancies were most common (59).

Conclusions: The number of malignancies in the LTS study was similar to that expected from an IBD population with no statistically significant differences, although few confounders could be corrected for. Limitations of PM safety reporting require consideration; however, the number of malignancies with vedolizumab appeared low.


In patients with Crohn's disease (CD), it has been estimated that the risk of colorectal, upper gastrointestinal (GI) and small bowel cancers is increased 1.9–2.5-fold, 2.9-fold and 27.1-fold, respectively, vs the background population.[1,2] In patients with ulcerative colitis (UC), the risk of colorectal and hepatobiliary cancers is estimated to be 2.4-fold and 2.6-fold higher, respectively, than the general population.[2,3] No unequivocal excess risk of extra-intestinal cancer has been established in patients with CD or UC; however, one study found increased risk at specific anatomical sites, including lungs, urinary bladder and skin, in patients with CD, and increased risk of leukaemia in patients with UC, but no significant increase overall.[2] A further study found increased lymphoma rates in men with CD vs healthy controls.[4] However, estimates were not adjusted for relevant risk factors, such as smoking or previous treatment exposure, in either study.

In addition to the impact of underlying disease, it is important to consider the possibility of increased risk of malignancy associated with treatments intended to reduce GI tract inflammation in CD or UC. Immunomodulators, including thiopurines and biologics (such as infliximab and other anti-tumour necrosis factor alpha [TNFα] antibodies), are commonly used to treat moderate-to-severe active disease.[5] Many treatments have been associated with increased malignancy risk in patients with inflammatory bowel disease (IBD), notably thiopurines; for example, one meta-analysis found a 4.9-fold increase in the incidence of lymphoma.[6] Notably, infliximab carries a "black box" warning regarding malignancies.[7] Furthermore, a population-based cohort study found that long-term (>12 months) immunosuppression was associated with increased risk of haematologic cancer, non-Hodgkin lymphoma, squamous cell skin cancer and overall cancer, primarily attributable to thiopurine use.[8] In contrast, a registry-based cohort study found no significant increase in cancer risk for patients with IBD receiving anti-TNFα therapy vs no anti-TNFα therapy over a median follow-up of 3.7 years.[9]

Vedolizumab is a gut-selective antibody to α4β7 integrin approved to treat moderate-to-severe active CD or UC in adults.[10–12] Integrated safety data from six vedolizumab trials have shown a low incidence of malignancy,[13] although trial follow-up periods and patient numbers were insufficient to evaluate this fully. Since first approval, additional safety data reflecting longer-term use of vedolizumab have been collected in an open-label extension study (GEMINI long-term safety [LTS] study; NCT00790933)[14,15] and the vedolizumab Global Safety Database (GSDB), through individual case safety reports from post-marketing (PM) sources. Given the importance of understanding malignancy risk associated with IBD treatments, this analysis aims to provide further evidence on whether there is an increased incidence of malignancy in patients with CD or UC receiving vedolizumab.