The efficacy of Vedolizumab ( Entyvio ), an alpha4beta7 integrin antibody, in Crohn's disease is unknown.
In an integrated study with separate induction and maintenance trials, researchers have assessed intravenous Vedolizumab therapy ( 300 mg ) in adults with active Crohn's disease.
In the induction trial, 368 patients were randomly assigned to receive Vedolizumab or placebo at weeks 0 and 2 ( cohort 1 ), and 747 patients received open-label Vedolizumab at weeks 0 and 2 ( cohort 2 ); disease status was assessed at week 6.
In the maintenance trial, 461 patients who had had a response to Vedolizumab were randomly assigned to receive placebo or Vedolizumab every 8 or 4 weeks until week 52.
At week 6, a total of 14.5% of the patients in cohort 1 who received Vedolizumab and 6.8% who received placebo were in clinical remission ( i.e., had a score on the Crohn's Disease Activity Index [ CDAI ] of less than or equal to 150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity ) ( P=0.02 ); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response ( greater than or equal to 100-point decrease in the CDAI score ) ( P=0.23 ).
Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to Vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo ( P less than 0.001 and P=0.004 for the two Vedolizumab groups, respectively, versus placebo ).
Antibodies against Vedolizumab developed in 4.0% of the patients.
Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving Vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events ( 24.4% vs. 15.3% ), infections ( 44.1% vs. 40.2% ), and serious infections ( 5.5% vs. 3.0% ).
In conclusion, Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive Vedolizumab ( rather than switching to placebo ) were more likely to be in remission at week 52.
Adverse events were more common with Vedolizumab. ( Xagena )
Sandborn WJ et al, N Engl J Med 2013; 369:711-721