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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
142
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Atlantic Children's Health-Goryeb Children's Hospital
Morristown, New Jersey, United States
Cohen Children's Medical Center of NY, Northwell
New York, New York, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Hvidovre University Hospital
Copenhagen, Denmark
Our Lady's Children's Hospital Crumlin
Dublin, Ireland
Rambam Medical Cener
Haifa, Israel
Wolfson Medical Center
Holon, Israel
Shaare Zedek Medical Center
Jerusalem, Israel
Schneider Medical Center
Petah Tikva, Israel
...and 5 more locations
Complete remission at week 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)
Time frame: weeks 14
Complete remission at week 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)
Time frame: weeks 30
Complete remission at week 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)
Time frame: weeks 54
Complete remission at week 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)
Time frame: weeks 108
Complete remission at week 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)
Time frame: weeks 162
Steroid and EEN free clinical remission (without the need for normal CRP) using PCDAI or PUCAI score and concomitant medication list.
Time frame: 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.
Time frame: week 30, week 54, week 108, week 162
Fecal calprotectin levels
Levels of calprotectin will be measured in the lab using calprotectin kit.
Time frame: week 30, week 54, week 108, week 162
serum CRP levels
CRP levels will be measured in the lab
Time frame: week 30, week 54, week 108, week 162
Rate of loss of response including drug levels
Time frame: week 30, week 54, week 108, week 162
Steroid dependency (defined as cumulative use of >4 months in a year with at least one need to increase dose while weaning)
Time frame: week 30, week 54, week 108, week 162
Adverse events
Time frame: 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.
Time frame: week 30, week 54, week 108, week 162
Time to induction of remission
Time frame: week 30, week 54, week 108, week 162
Longitudinal Physician Global Assessment (PGA)
PGA will be measured using Visual analogue scale (VAS)
Time frame: week 30, week 54, week 108, week 162
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Height velocity as compared with the year prior to commencing VDZ
Time frame: week 30, week 54, week 108, week 162
Need for surgical interventions (including resections, colectomy, and dilatations)
Time frame: week 30, week 54, week 108, week 162