Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease.

BACKGROUND: Vedolizumab specifically recognises the α4β7 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut-specific immunosuppression.

AIM: To review the safety of vedolizumab and summarise post-marketing data to assess if any safety concerns that differ from registration trials have emerged.

METHOD: A systematic bibliographic search identified six registration trials and nine cohort studies.

RESULTS: Integrated data from registration trials included 2830 vedolizumab-exposed patients (4811 person-years exposure [PYs]) and 513 placebo patients. This reported lower exposure-adjusted incidence rates of infection (63.5/100 PYs; 95% CI: 59.6-67.3) and serious adverse events (20.0/100 PYs; 95% CI: 18.5-21.5) compared to placebo (82.9/100 PYs; 95% CI: 68.3-97.5) and (28.3/100 PYs 95% CI: 20.6-35.9) respectively. Higher, but statistically insignificant rates of enteric infections occurred in vedolizumab-exposed patients (7.4/100 PYs; 95% CI: 6.6-8.3) compared to placebo (6.7 PYs; 95% CI: 3.2-10.1). Six post-marketing cohort studies (1049 patients, 403 PYs) demonstrated rates of infection of 8% (82/1049); enteric infection of 2% (21/1049) and adverse events of 16% (166/1049). Multivariate analysis in one cohort study suggested increased risk of surgical site infection with perioperative VDZ. Human experience in pregnancy is limited.

CONCLUSIONS: Post-marketing data confirm the excellent safety of vedolizumab observed in registration trials. The signal of post-operative complications should be interpreted with caution, but warrants further study. Although comparative studies are needed, Vedolizumab may be a safe alternative in patients who best avoid systematic immunosuppression, including those pre-disposed to infection, malignancy or the elderly.