Key messages
– Vedolizumab is effective in inducing and maintaining remission in people with Crohn's disease when compared to placebo (a dummy treatment).
– People receiving vedolizumab are probably no more likely than people receiving placebo to experience side effects, and may be no more likely to experience serious side effects, during induction or maintenance treatment.
What did we want to find out?
Crohn's disease is a chronic inflammatory condition affects the gastrointestinal tract (the gut). Vedolizumab is called a 'biological' medication that blocks an important protein called α4β7 that is involved in gut inflammation and results in gut-selective anti-inflammatory activity. We wanted to find out whether vedolizumab is effective and safe in treating Crohn's disease.
What did we do?
We searched for studies that compared vedolizumab to placebo in people with Crohn's disease. We compared and summarised their results, and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found four studies including 1126 participants that investigated vedolizumab's effect in inducing remission (where the disease is no longer active), and three studies including 894 participants that investigated its effect in maintaining remission.
Compared to placebo, vedolizumab was more effective at inducing remission (4 studies in 1126 participants) and maintaining remission (3 studies in 894 participants) in Crohn's disease. Vedolizumab is more effective than placebo for inducing a clinical response (i.e. disease entering remission; 4 studies in 1126 participants). It is probably as likely as placebo to cause overall side effects and as likely as placebo to cause serious side effects during both induction (4 studies in 1126 participants) or maintenance treatment (3 studies in 894 participants).
What are the limitations of the evidence
We are highly certain about the evidence for induction and maintenance of remission. However, there were limitations in comparing vedolizumab to placebo for serious and overall side effects due to our low confidence in the results.
How up-to-date is this evidence?
The evidence is up to date to November 2022.
High-certainty data across four induction and three maintenance trials demonstrate that vedolizumab is superior to placebo in the induction and maintenance of remission in Crohn's disease. Overall adverse events are probably similar and serious adverse events may be similar between vedolizumab and placebo during both induction and maintenance phases of treatment. Head-to-head research comparing the efficacy and safety of vedolizumab to other biological therapies is required.
Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and inflammatory bowel disease in general. This systematic review and meta-analysis summarises the current evidence of vedolizumab in the induction and maintenance of remission in Crohn's disease.
To evaluate the benefits and harms of vedolizumab versus placebo for the induction and maintenance of remission in people with Crohn's disease.
We used standard, extensive Cochrane search methods. The latest search date was 30 November 2022.
We included randomised controlled trials (RCTs) and quasi-RCTs comparing vedolizumab to placebo for the induction or maintenance of remission in people with Crohn's disease.
We used standard Cochrane methods. For induction studies, the primary outcome was 1. clinical remission, and secondary outcomes were rates of 2. clinical response, 3. adverse events, 4. serious adverse events, 5. surgery, 6. endoscopic remission and 7. endoscopic response. For maintenance studies, the primary outcome was 1. maintenance of clinical remission, and secondary outcomes were rates of 2. adverse events, 3. serious adverse events, 4. surgery, 5. endoscopic remission and 6. endoscopic response. We used GRADE to assess certainty of evidence.
We analysed induction (4 trials, 1126 participants) and maintenance (3 trials, 894 participants) studies representing people across North America, Europe, Asia and Australasia separately. One maintenance trial administered subcutaneous vedolizumab whilst the other studies used the intravenous form. The mean age ranged between 32.6 and 38.6 years.
Vedolizumab was superior to placebo for the induction of clinical remission (71 more per 1000 with clinical remission with vedolizumab; risk ratio (RR) 1.61, 95% confidence interval (CI) 1.20 to 2.17; number needed to treat for an additional beneficial outcome (NNTB) 13; 4 studies; high-certainty evidence) and superior to placebo for inducing clinical response (105 more per 1000 with clinical response with vedolizumab; RR 1.43, 95% CI 1.19 to 1.71; NNTB 8; 4 studies; high-certainty evidence). For the induction phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (9 fewer serious adverse events per 1000 with vedolizumab; RR 0.91, 95% CI 0.62 to 1.33; 4 studies; low-certainty evidence) and probably equivalent to placebo for overall adverse events (6 fewer adverse events per 1000 with vedolizumab; RR 1.01, 95% CI 0.93 to 1.11; 4 studies; moderate-certainty evidence).
Vedolizumab was superior to placebo for the maintenance of clinical remission (141 more per 1000 with maintenance of clinical remission with vedolizumab; RR 1.52, 95% CI 1.24 to 1.87; NNTB 7; 3 studies; high-certainty evidence). During the maintenance phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (3 fewer serious adverse events per 1000 with vedolizumab; RR 0.98, 95% CI 0.68 to 1.39; 3 studies; low-certainty evidence) and probably equivalent to placebo for the development of overall adverse events (0 difference in adverse events per 1000; RR 1.00, 95% CI 0.94 to 1.07; 3 studies; moderate-certainty evidence).