The alpha4beta7 integrin monoclonal antibody Vedolizumab ( Entyvio ) is hypothesised to be gut selective. Effects of Vedolizumab on immune responses to parenterally or enterally administered antigens were investigated.
In a randomised, double-blind, placebo-controlled, phase I trial, healthy participants received a single intravenous dose of Vedolizumab 750 mg ( n=64 ) or placebo ( n=63 ).
After 4 days, participants began intramuscular hepatitis B vaccine ( HBV; days 4, 32, 60 ) and oral cholera vaccine ( OCV; days 4, 18 ) regimens.
The study was designed to demonstrate a 15% non-inferiority margin for the between-group difference in the primary end point: percentage of participants with HBV seroconversion at day 74 ( serum hepatitis B surface antigen [ HBs ] antibody titre greater than or equal to 10 IU/L ).
OCV seroconversion at day 74 ( greater than 4-fold increase in serum cholera toxin [ CT ] antibodies ) was a secondary end point.
A total of 56 ( 90.3% ) placebo-treated and 54 ( 88.5% ) Vedolizumab-treated participants responded to HBV.
Geometric mean anti-HBs titres were similar for placebo ( 114.4 IU/L ) and Vedolizumab ( 129.6 IU/L ) at day 74.
A total of 60 ( 96.8% ) placebo-treated and 52 ( 82.5% ) Vedolizumab-treated participants responded to OCV at day 74.
Geometric mean anti-CT IgG levels were higher for placebo than for Vedolizumab at day 74 ( 9210.08 vs 3007.8 ELISA Units ( EU )/mL ) and day 32 ( 11629.3 vs 1575.4 EU/mL ).
Anti-CT IgA results were similar.
Adverse events were consistent with previous experience. One serious adverse event ( spontaneous abortion ) was reported for placebo.
In conclusion, Vedolizumab did not alter the response to parenterally administered antigens but reduced the response to oral antigens, demonstrating its gut-selective mechanism of action. ( Xagena )
Wyant T et al, Gut. 2014; Epub ahead of print