Crohn's Disease, Inflammatory Bowel Disease, Ulcerative Colitis
Conditions
Keywords
VDZ: Vedolizumab, UC: Ulcerative colitis, CD: Crohn's disease, TDM: Therapeutic drug monitoring
Brief summary
Vedolizumab (VDZ) is a humanized immunoglobulin G1 monoclonal antibody acting against α4β7 integrin which modulates lymphocyte trafficking in the gut. Results from the adult GEMINI-1 and GEMINI-2 trials demonstrated clinical efficacy in induction and maintenance of remission in both ulcerative colitis (UC) and Crohn's disease (CD), respectively. Recent real life cohorts in adults support the effectiveness of VDZ in inducing and maintaining remission, both in CD and UC. In pediatrics, there are very limited data on the use of VDZ besides two retrospective case series. Data on immunogenicity and therapeutic drug monitoring (TDM) of VDZ is conflicting in adults and practically non-existent in children. The investigators aim to prospectively explore the real life short and longer term outcomes of VDZ in pediatric IBD (including growth) and to develop a prediction model for treatment success based on VDZ trough levels and other clinical and laboratory variables.
Detailed description
This is a multi-center prospective cohort study in which the investigators are aim to enroll 140 children under the age of 18 years, diagnosed with CD, inflammatory bowel disease unclassified (IBDU) or UC (approximately 70 in UC/IBDU and 70 in the CD group) who commenced on Vedolizumab for any reason at the discretion of the treating physician. Patients will be followed up to 3 years at 8 different time points: week 0, week 2, week 6, week 14, week 30, week 54 (1 year), week 108 (2 years) and week 162 (3 years). Blood work will be collected at each visit during the time of venous access insertion for the drug infusion for serum and stool sample will be collected at visits 0, 14, 30, and 54. In addition, at week 0 and 14 whole blood will be collected into a PaxGene tube for gene expression analysis.
Interventions
DRUGVedolizumab
Sponsors
Shaare Zedek Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Children under the age of 18 years. 2. IBD Diagnosis 3. Initiating Vedolizumab therapy
Exclusion criteria
1\. Starting Vedolizumab to prevent post operative recurrence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission at week 14 | weeks 14 | As defined by all three criteria: i. Steroids and Exclusive enteral nutrition (EEN) (defined as \>50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) \<12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) \<10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing) |
| Complete remission at week 30 | weeks 30 | As defined by all three criteria: i. Steroids and Exclusive enteral nutrition (EEN) (defined as \>50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) \<12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) \<10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing) |
| Complete remission at week 54 | weeks 54 | As defined by all three criteria: i. Steroids and Exclusive enteral nutrition (EEN) (defined as \>50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) \<12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) \<10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing) |
| Complete remission at week 108 | weeks 108 | As defined by all three criteria: i. Steroids and Exclusive enteral nutrition (EEN) (defined as \>50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) \<12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) \<10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing) |
| Complete remission at week 162 | weeks 162 | As defined by all three criteria: i. Steroids and Exclusive enteral nutrition (EEN) (defined as \>50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) \<12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) \<10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Steroid dependency (defined as cumulative use of >4 months in a year with at least one need to increase dose while weaning) | week 30, week 54, week 108, week 162 | — |
| Adverse events | week 30, week 54, week 108, week 162 | — |
| Measures of mucosal inflammation as available as part of clinical care using endoscopy, imaging or capsule endoscopy. | week 30, week 54, week 108, week 162 | — |
| Steroid and EEN free clinical remission (without the need for normal CRP) using PCDAI or PUCAI score and concomitant medication list. | week 30, week 54, week 108, week 162 | — |
| Longitudinal Physician Global Assessment (PGA) | week 30, week 54, week 108, week 162 | PGA will be measured using Visual analogue scale (VAS) |
| Height velocity as compared with the year prior to commencing VDZ | week 30, week 54, week 108, week 162 | — |
| Need for surgical interventions (including resections, colectomy, and dilatations) | week 30, week 54, week 108, week 162 | — |
| Time to induction of remission | week 30, week 54, week 108, week 162 | — |
| Steroid and EEN free clinical response (without the need for normal CRP) using PCDAI or PUCAI score and concomitant medication list. | week 30, week 54, week 108, week 162 | — |
| Fecal calprotectin levels | week 30, week 54, week 108, week 162 | Levels of calprotectin will be measured in the lab using calprotectin kit. |
| serum CRP levels | week 30, week 54, week 108, week 162 | CRP levels will be measured in the lab |
| Rate of loss of response including drug levels | week 30, week 54, week 108, week 162 | — |
Countries
Denmark, Ireland, Israel, Slovenia, United Kingdom, United States
Outcome results
None listed