Clinical trial NCT06584162: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Inflammatory Bowel Diseases
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2024-09-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


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.

Primary outcomes:
measure: Cost-effectiveness
timeFrame: 48 weeks
Secondary outcomes:
measure: Difference in Quality of Life
timeFrame: multipe times between baseline and 48 weeks
measure: Biochemical parameters
timeFrame: multipe times between baseline and 48 weeks
measure: Biochemical parameters
timeFrame: multipe times between baseline and 48 weeks
measure: Pharmacokinetic aspects
timeFrame: multipe times between baseline and 48 weeks
measure: Pharmacokinetic aspects
timeFrame: multipe times between baseline and 48 weeks
measure: Difference in Quality of Life
timeFrame: multipe times between baseline and 48 weeks
measure: Clinical outcomes
timeFrame: multipe times between baseline and 48 weeks
measure: Clinical outcomes
timeFrame: multipe times between baseline and 48 weeks
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
Study officials:
affiliation: Amsterdam UMC
name: G.R.A.M. D'Haens, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: