Long-term clinical experience with Vedolizumab in patients with mildto moderate Ulcerative Colitis

Background: Binding of mucosal addressin cell adhesion molecule‐1 (MAdCAM‐1) by alpha 4beta7 mediates migration of leukocytes into gastrointestinal mucosa andassociated lymphoid tissue. Vedolizumab (VDZ) (previous versions MLN0002, MLN02, LDP‐02) is an investigational gut‐selective biologic that antagonizes a4b7.We describe the long‐term clinical experience of 53 patients with mild to moderateulcerative colitis (UC) who received VDZ for up to 2.5 years. Methods: UC patients were randomized to receive VDZ (2, 6, or 10 mg/kg) orplacebo on days 1, 15, 29, and 85 in a dose‐ranging study (DRS), after which (day253) they could continue to receive VDZ 2 mg/kg q8 weeks in an open‐label, long‐term extension study (ES) for up to an additional 547 days. Partial Mayoscore (PMS) was used to assess response to therapy through the final study visit(90 days after last dose). Safety, pharmacokinetics, pharmacodynamics, and immunogenicitywere assessed at multiple time points. At ES completion, subjectswere eligible to continue to receive VDZ in an ongoing, phase 3 safety extensiontrial (experience not included). Results: 38 patients received VDZ during the DRS and all continued in the ES.An additional 15 treatment‐naive patients were enrolled in the ES. 43 patients(81%) completed the ES. Reasons for discontinuation were lack of efficacy (n=5), adverse event (n=3) and withdrawal of consent (n=2). Pretreatment mean (SD)PMS was 3.7 (1.43) for the DRS and 5.4 (1.88) for the ES. At day 491 of the ES(before patients began enrolling into phase 3 ES), the mean (SD) PMS was 0.8(1.15), and 88% of patients (n=43) were in clinical remission. Mean (SD) exposureto VDZ was 580.3 (167.2) days. During the ES, 70% of patients reported >1 adverse event (AE); 9% reported >1 serious AE. The most common AEs were nasopharyngitis(15%), headache (8%), cough (8%), arthralgia (4%) and URI (4%). Onepatient required hospitalization for a self‐limited viral gastroenteritis, but no otherserious infections were reported. One serious infusion reaction occurred in apatient who had been exposed to VDZ in a previous clinical trial. 3 patients (6%)developed human anti‐human antibody to VDZ. There were no cases of progressivemultifocal leukoencephalopathy or deaths during either study. Mean pre‐infusionserum VDZ concentrations were dose proportional and remained steady anddetectable throughout the study with nearly full inhibition of a4b7 receptors. 29patients (55%) elected to continue to receive VDZ in the phase 3 ES. Conclusions: Long‐term VDZ administration was well tolerated, with a highrate of study completion. 2.0 mg/kg q 8 wks achieved target receptor saturationand was associated with durable mean decreases in disease activity.