Subcutaneous Interval Lengthening of Vedolizumab for Economic Research
NCT Number: NCT06584162
Acronym: SILVER
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Inflammatory Bowel Diseases
Interventions: DRUG: Vedolizumab Injection
Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2023-02-09
Completion Date: 2026-02-01
Locations: Amsterdam UMC, Amsterdam, Netherlands

Summary:
Rationale: Subcutaneous vedolizumab is an effective maintenance therapy for patients with inflammatory bowel disease. Patients using subcutaneous vedolizumab (every 2 weeks) have higher vedolizumab serum trough concentrations than those who are treated with intravenous vedolizumab (every 4-8 weeks). Since biologic therapies such as vedolizumab are expensive, lengthening of the injection interval (de-escalation) is of interest to reduce health care costs. However, maintaining remission while extending vedolizumab injection intervals has not been evaluated yet but represents a critical component of both medical and societal costs. Studies have suggested that higher vedolizumab serum concentrations are associated with superior clinical outcomes. Our strategy is to administer subcutaneous vedolizumab with prolonged intervals using therapeutic drug monitoring, i.e. dose based on vedolizumab concentrations, to reduce medical and societal costs while preserving remission.

Objectives: To evaluate whether subcutaneous vedolizumab therapeutic drug monitoring (TDM)-guided de-escalation will be cost-effective, compared to normal dosing regimen in patients with inflammatory bowel disease in remission. The secondary objective is to investigate the efficacy of TDM-guided de-escalation subcutaneous vedolizumab dosing compared to standard dosing.

Study design: This is a single-centre, randomized controlled, open-label pilot study.

Study population: 40 patients with inflammatory bowel disease (Crohn's disease or ulcerative colitis) in steroid-free clinical and biochemical remission with subcutaneous vedolizumab maintenance therapy of 108 mg every other week for at least 6 months.

Intervention: Patients will be randomized (1:1) to the 'TDM-guided subcutaneous vedolizumab de-escalation' strategy versus 'standard care' (e.g. continuing standard subcutaneous vedolizumab dosing regimen of 108 mg every other week).

Main study parameters/endpoints: Primary endpoint: cost-effectiveness of the TDM-guided de-escalation group compared to the standard dosing group over 48 weeks. Secondary endpoints include: proportion of patients with sustained clinical remission (based on Harvey-Bradshaw Index or Simple Clinical Colitis Activity Index), proportion of patients with (sustained) biochemical remission (based on c-reactive protein and fecal calprotectin), pharmacokinetic differences (vedolizumab levels and immunogenicity), safety and quality of life (measured by SIBDQ and EQ-5D-5L).

Primary Outcome Measures: Cost-effectiveness, Medical and societal expenses will be measured troughout the study. The primary outcome is at the end of the study at Week 48. Cost-effectiveness will be measured by using a cost-questionnaire developed with the health economics department, including health-related, work-related and societal costs., 48 weeks
Secondary Outcome Measures: Difference in Quality of Life, Quality of life will be measured by EQ-5D-5L questionnaire, multipe times between baseline and 48 weeks|Biochemical parameters, CRP, multipe times between baseline and 48 weeks|Biochemical parameters, Fecal calprotectin, multipe times between baseline and 48 weeks|Pharmacokinetic aspects, Vedolizumab concentrations, multipe times between baseline and 48 weeks|Pharmacokinetic aspects, Anti-drug antibodies, multipe times between baseline and 48 weeks|Difference in Quality of Life, Quality of life will be measured by SIBDQ, multipe times between baseline and 48 weeks|Clinical outcomes, Clinical outcomes will be measured troughout the study. For ulcerative colitis patients: Simple Clinical Colitis Activity Index., multipe times between baseline and 48 weeks|Clinical outcomes, Clinical outcomes will be measured troughout the study. For Crohn\&#39;s disease patients: Harvey-Bradshaw Index., multipe times between baseline and 48 weeks