291trial showing reduced seroconversion following oral cholera vaccination against
cholera toxin but no attenuation of serological response to parenteral hepatitis B
vaccination following a single 750 mg dose of vedolizumab [ 51 ]. In the GEMINI
trials, enteric infections (Clostridium difficile in six patients, Campylobacter in
three and Salmonella in one) occurred after vedolizumab but not placebo [ 42 , 43 ,
45 ]. Although the real potential for gut-specific immune inhibition to predispose to
enteric infection will be borne out in the fullness of time, clinicians must remain
vigilant with patients living in or travelling to the tropics and possibly in patients
with risk factors for Clostridium difficile infection. Until recently there were no data
that existed on the transmission of infection by live vaccines in patients receiving
vedolizumab. The FDA label indicates that patients receiving the medication should
receive live vaccines only if the benefits outweigh the risks. Wichmann et al. recently
reported a case of a patient with Crohn’s ileocolitis successfully vaccinated against
measles virus while on vedolizumab [ 52 ]. This anecdotal success with a live vaccine
on gut vedolizumab therapy despite making mechanistic sense needs to be studied
further.
Practical Clinical Considerations
Vedolizumab has emerged as a viable, efficacious and indeed attractive option in the
expanding biological armamentarium for IBD therapeutics. It is crucial for clini-
cians to understand how this drug will integrate into clinical practice with inevitable
comparisons drawn with anti-TNF agents. Bayesian network meta-analyses aim to
address this through indirect comparisons with a common comparator but are lim-
ited by the heterogeneity of patient populations studied and study design [ 53 – 55 ].
In one network meta-analysis of eight RCTs, the odds ratio for inducing remission
in UC was comparable for anti-TNF agents and vedolizumab [ 55 ]. One network
meta-analysis comparing vedolizumab to other biological therapies in CD found no
significant differences [ 53 ], whereas another ranked infliximab as the most effica-
cious agent for induction (86%) and adalimumab for maintenance of remission
(48%) [ 54 ].
Although induction efficacy of vedolizumab in Crohn’s disease at 6 weeks
appears to be less compelling, clinicians must pause to consider certain caveats in
extrapolating from these results. Indeed, although clinical remission in CD was
superior to placebo, no difference in CDAI-100 response or CRP was noted follow-
ing induction [ 43 ]. It seems likely that the timing of assessment was the limiting
factor as evidenced by the GEMINI III trial, wherein vedolizumab was superior to
placebo for induction of remission at 10 weeks but not at 6 weeks, in patients who
had previously failed anti-TNF therapy [ 45 ]. For maintenance of remission at
52 weeks, vedolizumab demonstrated superiority over placebo, with a magnitude of
effect generally similar to that seen in UC [ 42 , 43 , 45 ]. Thus, although induction
data with CD from trials are less compelling, the clearly clinically meaningful effect
after 30 weeks suggests that vedolizumab is an appropriate option in well-selected
16 Anti-integrin Agents in IBD: Efficacy and Risk of Complications