Vedolizumab affects antibody responses to immunisation selectively in the gastrointestinal tract: randomised controlled trial results.
OBJECTIVE
The α4β7 integrin monoclonal antibody vedolizumab is hypothesised to be gut selective. Effects of vedolizumab on immune responses to parenterally or enterally administered antigens were investigated.


METHODS
In this 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 ≥10 IU/L). OCV seroconversion at day 74 (>4-fold increase in serum cholera toxin (CT) antibodies) was a secondary end point.


RESULTS
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.


CONCLUSIONS
Vedolizumab did not alter the response to parenterally administered antigens but reduced the response to oral antigens, demonstrating its gut-selective mechanism of action.


BACKGROUND
NCT Number: 01981616; EudraCT Number: 2011-001874-24.
Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, USA.
Tim
T
Wyant
Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, USA.
Tim
T
Leach
Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, USA.
Serap
S
Sankoh
Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, USA.
Yuemei
Y
Wang
University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Jonathan
J
Paolino
Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Marcela F
MF
Pasetti
Department of Medicine and Department of Epidemiology and Biostatistics, Robarts Clinical Trials, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
Brian G
BG
Feagan
Takeda Pharmaceuticals International, Inc, Deerfield, Illinois, USA.
Asit
A
Parikh
D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000917:Antibody Formation / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology; D006801:Humans; D007114:Immunization; D008297:Male; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; D017325:Hepatitis B Vaccines; C543529:vedolizumab
Antibody Targeted Therapy; Gut Immunology; Inflammatory Bowel Disease