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patients in whom the concomitant use of bridging strategies (such as co-induction
with steroids) is possible and where surgery may not be more appropriate. Indeed,
it might also be a first-line biologic option in patients where the focus is safety, for
example, in young or elderly patients with IBD [ 56 – 58 ]. The role of vedolizumab in
treatment of perianal disease is unclear. At 52 weeks in GEMINI II, 41.2% of the
vedolizumab 8-weekly group achieved fistula closure compared with 22.7% of the
vedolizumab 4-weekly group and 11.1% of the placebo group (p = 0.03, p = 0.32
versus placebo, respectively) [ 43 ]. This borderline significance needs further inves-
tigation. Indeed, a higher incidence of perianal abscesses was reported in prelimi-
nary data from the GEMINI-LTS extension study [ 49 ].
The safety and efficacy profile for UC may be regarded as more favourable, posi-
tioning vedolizumab as a potential first-line biologic for induction and maintenance
of remission in outpatients with moderate to severe UC, who have failed or had an
inadequate response to corticosteroids or immunosuppressant therapy. It cannot be
recommended at the present time for the treatment of acute severe UC due to its
relative slow onset of action and in the absence of data for this indication. There are
no data for the perioperative safety and efficacy of vedolizumab in CD, and although
the mechanism of action of vedolizumab, preventing early stages of inflammation,
is appealing, clinical trials are needed to provide credible evidence. There are no
data in patients with extra-intestinal manifestations of IBD. Although it seems
implausible that a gut-selective agent should benefit those manifestations that do not
parallel IBD activity (such as pyoderma gangrenosum or ankylosing spondylitis),
manifestations associated with gut inflammation (e.g. erythema nodosum and
episcleritis) may benefit, and this merits further study.
More promising is the prospect of treating primary sclerosing cholangitis (PSC)
affecting 3–10% of IBD patients [ 59 , 60 ]. Hepatic inflammation in PSC is driven by
TNF-α and methylamines in the portal circulation and results in aberrant hepatic
expression of MAdCAM-1 and the chemokine CCL25 [ 60 ]. This leads to enhanced
recruitment of α 4 β7 and the CCL25 receptor CCR9. Randomised trials of VDZ in
patients with IBD–PSC are under way (clinicaltrials.gov NCT00783692 and
NCT01316939).
Although vedolizumab has not been associated with an increased risk of malig-
nancy, long-term experience is limited, and indeed patients with prior malignancy
were excluded from trials. Diminished gastrointestinal immune surveillance may
pose a theoretical concern for colorectal cancer complicating UC or small intestinal
adenocarcinoma in CD, given their increased risk relative to the general population.
Nonetheless, carcinogenesis is a likely consequence of inflammation, and it is not
implausible that control of inflammation by vedolizumab may reduce this risk [ 61 ,
62 ]. More research is needed in this area.
Vedolizumab is a pregnancy risk category B drug with limited data on safety in
pregnancy. In a series of 24 women exposed to vedolizumab during pregnancy, there
were 12 live births, five elective abortions and four spontaneous abortions [ 63 ].
With a half-life of 25 days, any strategy of withholding dosing in the third trimes-
ter could result in significant vedolizumab concentration in the foetus and pro-
longed drug clearance in the neonate potentially extending to 6–12 months, the
J.K. Limdi and F.A. Farraye