Yarur AJ¹, Bruss A², Naik S³, Beniwal-Patel P⁴, Fox C⁴, Jain A³, Berens B², Patel A⁴, Ungaro R⁵, Bahur B³, Dubinsky M⁵, Stein DJ⁴. Dig Dis Sci. 2019 Mar 5. doi: 10.1007/s10620-019-05570-1. [Epub ahead of print]

Author information

1 Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Hub for Collaborative Medicine, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA. ayarur@mcw.edu.

2 Clinical Translational Science Institute, Medical College of Wisconsin, Milwaukee, WI, USA.

3 Prometheus Laboratories Inc, San Diego, CA, USA.

4 Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Hub for Collaborative Medicine, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.

5 Icahn School of Medicine, Mount Sinai Hospital, New York, NY, USA.

Abstract

BACKGROUND: The aim of this study was to assess the relationship of serum vedolizumab concentrations (SVC) during induction and endoscopic remission in patients with inflammatory bowel diseases (IBD) after 52 weeks of therapy with vedolizumab. We also sought to assess the incidence of antibody to vedolizumab (ATV) formation, the effect of ATV on drug pharmacokinetics and efficacy, and identify variables associated with SVC through the first 30 weeks of treatment.

METHODS: This is a prospective cohort study of patients with active IBD initiating standard therapy with vedolizumab. Collected variables included demographics, clinical disease activity, biomarkers, pre-infusion SVC, and ATV measured at weeks 2, 6, 14, 22, and 30. Primary outcome was steroid-free endoscopic remission at week 52.

RESULTS: Fifty-five patients were included. Patients that achieved steroid-free endoscopic remission by week 52 had higher SVC at weeks 2, 6, 14, 22, and 30, but only achieved statistical significance at weeks 2 and 6. Only 3 out of the 55 study subjects (5.5%) had detectable ATV through the follow-up. Overall, there were a positive correlation between SVC and serum albumin and a negative correlation with C-reactive protein, fecal calprotectin, and body mass. Vedolizumab concentrations ≥ 23.2 mcg/ml at week 2 were associated with endoscopic remission at week 52 (OR 8.8 [95% CI 2.6-29.7], p < 0.001).

CONCLUSIONS: Vedolizumab concentrations during induction were associated with endoscopic remission at week 52. Interventional studies looking into improved efficacy with higher drug exposure are warranted.