BACKGROUND: Vedolizumab is a humanized immunoglobulin G1 monoclonal antibody that exclusively targets the lymphocyte integrin &agr;4&bgr;7. This interaction prevents the binding of gut-homing T lymphocytes to mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1), thus reducing gastrointestinal inflammation. Vedolizumab is currently in development for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD). Vedolizumab pharmacokinetic (PK) data from phase 3 studies (GEMINI 1 and 2) have been previously published and show similar PK profiles in UC and CD patient populations.1,2 Here the PK/pharmacodynamic (PD) relationship and immunogenicity of vedolizumab in the GEMINI 1 and 2 studies are described. METHODS: The GEMINI 1 and 2 studies included a 6-week induction phase, during which patients received vedolizumab 300 mg or placebo intravenously at weeks 0 and 2 and were assessed at week 6. Vedolizumab-treated patients who had a clinical response at week 6 were randomly assigned to receive vedolizumab 300 mg (vedolizumab intention-to-treat [ITT] population) or placebo (placebo ITT population) every 4 weeks (Q4W) or every 8 weeks (Q8W) during the subsequent 46-week maintenance phase. Vedolizumab induction nonresponders (non-ITT population) received open-label vedolizumab Q4W, and patients randomly assigned to placebo during the induction phase continued to receive placebo until week 52. Blood samples for determination of vedolizumab concentrations, PD assessment (&agr;4&bgr;7 [receptor] saturation via MAdCAM-1-Fc binding interference assay), and anti-vedolizumab antibody assessment were collected at prespecified time points. Descriptive statistics were used to summarize vedolizumab PK and immunogenicity data. Plots of receptor saturation were generated. RESULTS: Administration of vedolizumab 300 mg Q4W or Q8W resulted in mean serum concentrations ≥10 µg/mL at all time points in both UC and CD patients (ITT and non-ITT). In a pooled analysis of UC and CD patients (ITT and non-ITT), complete receptor saturation was observed at week 6 and maintained until week 52 in both the vedolizumab Q8W and Q4W groups. Overall, 4% (56/1434) of patients tested positive for anti-vedolizumab antibodies at any time during vedolizumab treatment. Frequency of anti-vedolizumab antibody development off drug (week 66) was ∼10% (32/320) in pooled UC and CD patients (ITT and non-ITT). Among patients who had an investigator-defined infusion-related reaction, 5% (3/61) tested persistently (at ≥2 consecutive visits) positive for anti-vedolizumab antibodies. Compared with the general study population, patients who tested persistently positive for anti-vedolizumab antibodies generally had lower serum vedolizumab trough concentrations. In the ITT placebo group, use of concomitant immunomodulators was associated with a lower rate of anti-vedolizumab antibody positivity (3%, 1/32) than seen without use of concomitant immunomodulators (18%, 44/247). CONCLUSIONS: Conclusions During dosing with vedolizumab either Q8W or Q4W in patients with UC and CD, mean vedolizumab serum concentrations were maintained at ≥10 µg/mL, a level that resulted in complete receptor saturation. References 1. Sandborn WJ, et al. N Engl J Med. 2013;369(8):711-721. 2. Feagan BG, et al. N Engl J Med. 2013;369(8):699-710.