BACKGROUND: Cellular adhesion molecules play an important role in the 
pathogenesis of ulcerative colitis, making selective blockade of these molecules 
a promising therapeutic strategy. Vedolizumab, a recombinant humanized IgG1 
monoclonal antibody, inhibits adhesion and migration of leukocytes into the 
gastrointestinal tract by binding the alpha4beta7 integrin. Animal studies have 
suggested that vedolizumab may be a useful therapy for ulcerative colitis. This 
updated systematic review summarizes the current evidence on the use of 
vedolizumab for induction and maintenance of remission in ulcerative colitis.
OBJECTIVES: The primary objectives were to determine the efficacy and safety of 
vedolizumab used for induction and maintenance of remission in ulcerative 
colitis.
SEARCH METHODS: A computer-assisted search for relevant studies (inception to 15 
June 2014) was performed using PubMed, MEDLINE, EMBASE and CENTRAL. References 
from published articles and conference proceedings were searched to identify 
additional citations.
SELECTION CRITERIA: Randomized controlled trials comparing vedolizumab to 
placebo or a control therapy for induction or maintenance of remission in 
ulcerative colitis were included.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and 
assessed the risk of bias for each trial. The primary outcomes were failure to 
induce clinical remission and relapse. Secondary outcomes included failure to 
induce a clinical response, failure to induce endoscopic remission, failure to 
induce an endoscopic response, quality of life, adverse events, serious adverse 
events and withdrawal due to adverse events. We calculated the relative risk 
(RR) and 95% confidence intervals (CI) for each outcome. Data were analyzed on 
an intention-to-treat basis. The overall quality of the evidence supporting the 
outcomes was evaluated using the GRADE criteria.
MAIN RESULTS: Four studies (606 patients) were included. All of the studies were 
rated as having a low risk of bias. Pooled analyses revealed that vedolizumab 
was significantly superior to placebo for induction of remission, clinical 
response, and endoscopic remission and prevention of relapse. After 4 to 6 weeks 
of therapy 77% (293/382) of vedolizumab patients failed to enter clinical 
remission compared to 92% (205/224) of placebo patients (RR 0.86, 95% CI 0.80 to 
0.91; 4 studies 606 patients). After 6 weeks of therapy 48% of vedolizumab 
patients failed to have a clinical response compared to 72% of placebo patients 
(RR 0.68, 95% CI 0.59 to 0.78; 3 studies 601 patients). After 4 to 6 weeks of 
therapy 68% of vedolizumab patients failed to enter endoscopic remission 
compared to 81% of placebo patients (RR 0.82, 95% CI 0.75 to 0.91; 3 studies, 
b583 patients). After 52 weeks of therapy, 54% of vedolizumab patients had a 
clinical relapse compared to 84% of placebo patients (RR 0.67, 95% CI 0.59 to 
0.77; 1 study, 373 patients). One small study (28 patients) found no 
statistically significant difference in endoscopic response (RR 1.00, 95% CI 
0.62 to 1.61). GRADE analyses indicated that the overall quality of the evidence 
for the primary outcomes was high for induction of remission and moderate for 
relapse (due to sparse data 246 events). There was no statistically significant 
difference between vedolizumab and placebo in terms of the risk of any adverse 
event (RR 0.99, 95% CI 0.93 to 1.07), or serious adverse events (RR 1.01, 95% CI 
0.72 to 1.42). There was a statistically significant difference in withdrawals 
due to adverse events. Six per cent of vedolizumab patients withdrew due to an 
adverse event compared to 11% of placebo patients (RR 0.55, 95% CI 0.35 to 0.87; 
2 studies, 941 patients). Adverse events commonly reported across the studies 
included: worsening ulcerative colitis, headache, nasopharyngitis, upper 
respiratory tract infection, nausea, and abdominal pain.
AUTHORS' CONCLUSIONS: Moderate to high quality data from four studies shows that 
vedolizumab is superior to placebo for induction of clinical remission and 
response and endoscopic remission in patients with moderate to severely active 
ulcerative colitis and prevention of relapse in patients with quiescent 
ulcerative colitis. Moderate quality data from one study suggests that 
vedolizumab is superior to placebo for prevention of relapse in patients with 
quiescent ulcerative colitis. Adverse events appear to be similar to placebo. 
Future trials are needed to define the optimal dose, frequency of administration 
and long-term efficacy and safety of vedolizumab used for induction and 
maintenance therapy of ulcerative colitis. Vedolizumab should be compared to 
other currently approved therapies for ulcerative colitis in these trials.