Subcutaneous Interval Lengthening of Vedolizumab for Economic Research

Official title

Subcutaneous Vedolizumab Drug De-escalation Using Therapeutic Drug Monitoring in Inflammatory Bowel Disease: a Randomized Controlled Pilot Study

Overview

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).

Interventions

• Drug Vedolizumab Injection
  Based on therapeutic drug monitoring, patients could be de-escalated based on a pharmacokinetic model: Dosing interval Trough Target 20 mg/L Adjust dosing interval to: 2 weeks \< 33 mg/L 2 weeks 2 weeks 33 - 46 mg/L 3 weeks 2 weeks ≥ 46 mg/L 4 weeks 3 weeks \< 20 mg/L 2 weeks 3 weeks 20 - 29 mg/L 3 weeks 3 weeks ≥ 29 mg/L 4 weeks 4 weeks \< 13 mg/L 2 weeks 4 weeks 13 - 20 mg/L 3 weeks Version number: 6.1, 24-06-2024 22 of 44 4 weeks ≥ 20 mg/L 4 week

Primary outcome measures

• Cost-effectiveness [Time frame: 48 weeks]

Secondary outcome measures (8)

• Difference in Quality of Life [Time frame: multipe times between baseline and 48 weeks]
• Biochemical parameters [Time frame: multipe times between baseline and 48 weeks]
• Biochemical parameters [Time frame: multipe times between baseline and 48 weeks]
• Pharmacokinetic aspects [Time frame: multipe times between baseline and 48 weeks]
• Pharmacokinetic aspects [Time frame: multipe times between baseline and 48 weeks]
• Difference in Quality of Life [Time frame: multipe times between baseline and 48 weeks]
• Clinical outcomes [Time frame: multipe times between baseline and 48 weeks]
• Clinical outcomes [Time frame: multipe times between baseline and 48 weeks]

Eligibility criteria

Inclusion criteria

• Diagnosis of Crohn's disease or ulcerative colitis
• Clinical and biochemical remission: absence of active inflammatory intestinal symptoms, fecal calprotectin <250 ug/g and CRP <5 mg/g, HBI <5 or SCCAI <4
• Steroid free remission for at least 6 months whilst being treated with subcutaneous vedolizumab at a stable dose of 108mg every other week.

Exclusion criteria

• Absence of written informed consent;
• Presence of anti-drug antibodies against vedolizumab, these levels will be determined in case the vedolizumab concentration is below 1 ug/ml;
• Concomitant oral glucocorticosteroid usage;
• Imminent need for IBD-related surgery as judged by the treating clinician;
• Actively draining peri-anal fistula;
• Patients with short bowel syndrome, an ostomy or a symptomatic stricture;
• Active participation in another interventional trial;
• Pregnancy or lactation;
• Other significant medical conditions that might interfere with this study (such as current/recent malignancy, immunodeficiency syndromes and psychiatric illness);
• Impossibility to measure outcomes, e.g. planned relocation, language issues, short life expectancy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 1 center

• Amsterdam UMC — Amsterdam

Identifiers

NCT: NCT06584162 · NL80854.018.22

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗