Real-world multicentre observational study including population pharmacokinetic modelling to evaluate the exposure-response relationship of vedolizumab in inflammatory bowel disease: ERELATE Study.

Abstract

ERELATE was a phase 4, multinational, retrospective, observational study. To evaluate the relationship between intravenous vedolizumab exposure and treatment outcomes over 52 weeks in adults with ulcerative colitis (UC) or Crohn's disease (CD). Real-world data from patients with UC or CD treated with intravenous vedolizumab in nine centres in six countries were collected retrospectively. Treatment outcomes were collected at Weeks 14, 26 and 52. An established population pharmacokinetic model (incorporating observed vedolizumab concentrations based on a Bayesian approach) was used to predict individual vedolizumab exposure. Vedolizumab exposure-response relationship was evaluated overall, by indication and based on baseline characteristics. The study population (n= 695; UC, n= 304; CD, n= 391) had a median age of 39 years; 47.9% were male and 86.9% had prior tumour necrosis factor antagonist exposure. By Week 14, clinical, endoscopic, deep (clinical plus endoscopic) and biologic remission was achieved by 47.3%, 59.6%, 30.7% and 19.0% of patients respectively. Higher vedolizumab trough concentration early in treatment was consistently associated with clinical remission at later time points. Clinical remission at Week 14 and Week 52 was associated with Week 6 trough concentrations of ≥31.0 and ≥32.0μg/ml respectively. Importantly, multivariable analysis identified baseline clearance as the only exposure measure predictive of clinical and deep remission at Week 52. In this real-world study, a positive exposure-response relationship was observed for vedolizumab. Vedolizumab concentration during induction may be an important predictor of short- and long-term outcomes, and similarly, vedolizumab baseline clearance may be an important predictor of remission.