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The GEMINI III trial enrolled patients with moderately to severely active CD,
the majority of who (76%) had failed anti-TNF therapy [ 45 ]. The primary endpoint
was clinical remission at week 6 in the anti-TNF failure subgroup. Secondary end-
points were clinical remission at week 10 and a CDAI-100 response at week 6 and
week 10. Of 315 patients with CD and anti-TNF intolerance or failure, 15.2% on
VDZ versus 12.1% on placebo achieved clinical remission at week 6 (p = 0.433). At
week 10, more patients on VDZ achieved remission compared with placebo (26.6%
versus 12.1%; 95% CI, 1.3–3.6; p < 0.001) [ 45 ]. Taken together, these three trials
indicate that VDZ is moderately effective both for UC and CD in a group of patients
refractory to conventional therapy including anti-TNF agents. It is noteworthy that
the onset of action is relatively slow, often requiring 10 weeks or more of therapy.
Safety and Efficacy
Data on clinical efficacy and safety from prospectively followed cohorts are now
available. In a recently reported GETAID study, patients with active IBD (CD = 173
and UC = 121), with an inadequate or loss of response to conventional therapy or at
least 1 anti-TNF agent, received standard induction and maintenance doses of
vedolizumab [ 46 ]. Concomitant use of corticosteroids, thiopurines or methotrexate
was permitted. At week 14, 31% of patients with CD were in steroid-free clinical
remission, and 51% had a response. Among patients with UC, 36% were in steroid-
free clinical remission, and 50% had a response. Severe adverse events occurred in
24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation
(pulmonary tuberculosis in one patient and rectal adenocarcinoma in another). No
deaths were reported [ 46 ]. Integrated long-term safety data (May 2009–June 2013)
from the vedolizumab studies [ 42 , 43 , 45 , 47 , 48 ] have recently been published and
show promising results [ 49 ]. Of 2830 patients with 4811 PYs of vedolizumab expo-
sure (median exposure range, 1–1977 days), there was no increased risk associated
with vedolizumab exposure. Clostridial infections, sepsis and tuberculosis were
reported infrequently (≤0.6% of patients). Independent risk factors for serious
infection in UC were prior failure of a TNF-α antagonist and narcotic analgesic use,
and in CD these were younger age and corticosteroid or narcotic analgesic use.
Eighteen vedolizumab-exposed patients (<1%) were diagnosed with a malignancy
including non-melanoma skin cancer, malignant melanoma, colon cancer, breast
cancer and renal, liver and lung cancer, with nearly all patients (except one with
renal cancer) having had prior exposure to thiopurines and or anti-TNF agents [ 49 ].
Vedolizumab demonstrated a favourable safety profile over an extended period [ 49 ].
A recent systematic review did not detect any significant increase in either opportu-
nistic infections or malignancy with either non-gut-specific or gut-specific anti-
integrin antibodies compared to placebo [ 50 ]. Reassuringly, no cases of PML have
been reported.
Much of the intrinsic appeal for vedolizumab lies in its gut selectivity without
systemic immunosuppression. This was elegantly demonstrated in a randomised
J.K. Limdi and F.A. Farraye