VDZ dosing for early non-responders

January 2, 2024

Issue 01

Clinical Question

Does dose optimization increase late vedolizumab response rates?

Editor’s Bottom Line

For patients with ulcerative colitis and primary non-response to vedolizumab, dose intensification does not appear to be any more effective than continuing with the standard dose.

Reference

Jairath V, Yarur A, Osterman MT, et, et al. ENTERPRET: a randomized controlled trial of vedolizumab dose optimization in patients with ulcerative colitis who have early nonresponse Clin Gastroenterol Hepatol. Epub ahead of print Nov 9, 2023;2023;165(4):963–75.e5; https://www.cghjournal.org/article/pdf

Synopsis

In this multicenter, phase 4 trial, 278 patients with moderate-to-severe ulcerative colitis received a standard induction regimen of vedolizumab in an open-label fashion, with 47.5% achieving clinical response at five weeks.

Researchers randomized 108 of the patients who did not experience response and had high drug clearance of vedolizumab, defined as a week five serum concentration 50 μg/mL, to receive either ongoing standard treatment or dose-optimized treatment.

Those randomized to standard treatment continued to receive 300 mg vedolizumab every eight weeks. Patients in the dose-optimized group received either 600 mg at week six followed by 300 mg every four weeks if their week five drug level was 30–50 μg/mL, or 600 mg at week six followed by 600 mg every four weeks if their week five vedolizumab concentration was <30 μg/mL.

The mean duration of disease in the standard and dose-optimized groups were 7.4 and 8.6 years, respectively. Additionally, 55% and 49% of the two groups, respectively, had pancolitis, 47.2% and 61.8%, respectively, had severe disease (defined as a complete Mayo score of 9–12) and 32% and 34.5%, respectively, had failed to respond to prior anti-tumor necrosis factor (TNF) treatment.

Pharmacokinetic findings showed that 16 weeks after randomization, those receiving dose-optimized vedolizumab had mean serum drug concentrations of 38.8–42.1 μg/mL, compared to 6.4 μg/mL in the standard dosing group.

Thirty weeks after the initial vedolizumab dose, 32.1% and 30.9% of patients randomized to either standard and dose-optimized treatment, respectively, experienced clinical response.

Nearly 19% of those in the standard vedolizumab treatment group experienced endoscopic improvement at week 30, compared to 14.5% in the dose-optimized group. Additionally, 9.4% of standard vedolizumab recipients achieved clinical remission at week 30, compared to 9.1% of those who received dose-optimized vedolizumab.

There were no significant differences in clinical or endoscopic outcomes between the two dose-optimized groups.

Similar numbers of patients in the study arms developed antibodies to vedolizumab and treatment safety was similar across arms and similar to the previously-reported safety profile of vedolizumab.

Details

Study Design: Controlled, open label
Funding: Takeda Pharmaceuticals
Allocation: Randomized
Setting: Multicenter
Level of Evidence: 1b