ENTERPRET: A Randomized Controlled Trial of Vedolizumab Dose Optimization in Patients With Ulcerative Colitis Who Have Early Nonresponse

Abstract

BACKGROUND & AIMSPatients with ulcerative colitis (UC) may experience nonresponse to biologics, possibly due to low drug exposure. This trial assessed the efficacy of dose optimization in patients with UC who have early nonresponse to vedolizumab and high drug clearance. METHODSENTERPRET was a phase 4, open-label, randomized controlled trial that included patients with moderate to severe UC who had high drug clearance at week 5 (serum concentration <50 μg/mL) and nonresponse to standard vedolizumab treatment at week 6. At week 6, eligible patients were randomized 1:1 to receive standard dosing (300 mg every 8 weeks) or dose-optimized vedolizumab (600 mg at week 6, then 300 mg every 4 weeks; or 600 mg at week 6, then 600 mg every 4 weeks [based on week 5 serum concentration]). The primary end point was endoscopic improvement at week 30. RESULTSOf 278 enrolled patients, 132 (47.5%) had a clinical response at week 6. From week 6, 108 patients received standard (n = 53) or dose-optimized vedolizumab (n = 55); among patients with nonresponse at week 6, 86.5% had high drug clearance. At week 30, 10 patients (18.9%) who received standard vedolizumab had endoscopic improvement versus 8 patients (14.5%) who received dose-optimized vedolizumab. Five patients (9.4%) who received standard vedolizumab had clinical remission at week 30 versus 5 patients (9.1%) who received dose-optimized vedolizumab; clinical response was observed in 17 (32.1%) and 17 patients (30.9%), respectively. Safety event rates were similar among treatment groups. CONCLUSIONSIn patients with early nonresponse and high drug clearance, vedolizumab dose optimization is probably not required. A proportion of patients benefited from continued treatment irrespective of the dose received. ClinicalTrials.gov Number: NCT03029143.