305ulcerative colitis [ 2 ]. After induction, vedolizumab-treated patients had greater rates
of response, remission, and mucosal healing at week 6 of the trial compared to pla-
cebo. These favorable data persisted at week 52 during the maintenance phase of the
trial. The maintenance phase included an every 4 week and every 8 week arm, both
which showed similar outcomes. There were no differences in adverse events among
the groups and no cases of PML were identified.
GEMINI II enrolled patients with moderate to severe Crohn’s disease [ 8 ]. After
induction, vedolizumab-treated patients achieved a statistical greater rate of remis-
sion at week 6, but missed the second co-primary endpoint, reduction in the Crohn’s
Disease Activity Index by 100 points. However at week 52 in the maintenance trial,
vedolizumab-treated patients had greater rates of clinical remission (primary end-
point) as well as other key outcomes (reduction in the CDAI by 100 points and
steroid-free remission). No cases of PML were identified; however, the incidence of
serious adverse events, infections, and serious infection was noted to be higher in
the vedolizumab-treated group. These were not further elaborated in the manuscript
and not seen in the ulcerative colitis clinical trial.
GEMINI III was an induction trial focusing on moderate-severe Crohn’s patients
who failed TNF therapy [ 10 ]. Patients received vedolizumab at 0, 2, and 6 weeks
and the primary outcome was measured at week 6. Although rates of remission
between the vedolizumab-treated group and placebo were similar at week 6, rates of
response were higher in the vedolizumab-treated group at this time point. The
vedolizumab-treated group achieved greater rates of remission not at week 6 but
several weeks after induction, at week 10. There were no differences in adverse
events in this induction trial and no cases of PML were identified.
Etrolizumab (Anti-α 4 β7 and αEβ7 Integrin, Monoclonal Ab, SC
Route, UC/CD)
Ertrolizumab is a monoclonal antibody with a dual anti-integrin mechanism of
action. It blocks the β7 subunit of both the α 4 β7 and αEβ7 integrins, resulting poten-
tially in a very novel mechanism of action compared to vedolizumab [ 11 ]. Besides
inhibiting gut-specific α 4 β7 lymphocytes from homing and migrating to the gut,
etrolizumab uniquely blocks the interaction between αEβ7 and E-cadherin [ 12 ]. The
E-cadherin gene has been implicated in IBD through genome-wide association stud-
ies. Cadherins are important in preserving intestinal barrier function. Thus, etroli-
zumab can have an additional beneficial effect of controlling inflammation at the
mucosal level by inhibiting αEβ7 lymphocytes from entering the epithelium [ 11 , 13 ].
The data for etrolizumab will be informed by an extensive and novel phase III
clinical trial program, for which studies are ongoing. In EUCALYPTUS, a phase II
randomized controlled trial, etrolizumab showed to be an effective induction agent
for moderate to severe UC [ 12 ]. More patients treated with etrolizumab were in
remission at week 10 compared to placebo. Adverse events occurred at a similar
frequency in the treated and placebo groups. Although no cases of PML were
17 Novel Agents in Inflammatory Bowel Disease