MILESTONE-CD -A Prospective Multiomic Inception Real -Life Study To Evaluate Predictors of Disease Outcomes & respoNse to Biologic Treatment in Crohn's Disease
MILESTONE-CD -A Prospective Multiomic Inception Real -Life Study To Evaluate Predictors of Disease Outcomes & respoNse to Biologic Treatment in Crohn's Disease
Crohn's' disease (CD) is a lifelong-chronic inflammatory condition of the digestive tract. CD frequently manifests during the 2nd or 3rd decade; prolonged disease duration frequently results in major structural complications such as strictures and fistulae, leading to surgery for control of complications in at least 30% of the patients. The course of disease is extremely diverse, ranging from a very mild disease to a devastating and incapacitating course. The burden of inflammatory bowel disease is growing each disease, reaching 400 billion USD for lifetime in US. In Israel, there are currently over 50000 IBD patients, with one of the highest incidences in the word, multiple treatment modalities and medications are available for Crohn's disease, however the efficacy is limited and the costs- very high. Furthermore, long-term exposure to some of the therapeutic agents poses an increased risk of infections and cancer.
Some of the major challenges in IBD include prediction of disease course (some patients will require early and aggressive treatment while others may just need observation and follow-up), and treatment personalization (right drug for the right patient at the right time). Unfortunately, individualized predictors of disease course and response to treatment are currently very limited. Some clues can be derived from imaging and endoscopy data, transcriptomics, genomic and microbiome, however those are still very premature and impractical. Moreover, large-scale studies with sophisticated predictive models that incorporate multilayered and multilayered clinical and omic data are severely lacking.
Goal:
Create comprehensive patient-multiomic profile (PRO-Visualosome-microbiome-transcriptome-pharmacokineticome) to develop algorithm-based personalized IBD therapy
Design Prospective observational cohort study.
Study aim To detect predictors of response to biologics using a layered multiomic approach
Cohort size Up to 140 patients in 2 years
Study duration -Patients will be followed up to 2 years (possible extension) or until treatment discontinuation or intestinal surgery
Study procedures All study procedures will be performed for the purpose of the study
Baseline
Disease activity using Harvey Bradshaw score at all timepoints and visits
First follow-up visit (12-14 weeks)
Every 3 months
- Home calprotectin (Calprosmart) +microbiome
Every 6 months
Upon failure (need to switch medication -defined by treating physician) or end of study
Clinic visit
Calprotectin *Home +ELISA)
Microbiome
Serum for transriptomics, metabolomics
Blood/serum for serum and cellular markers, drug levels, CRP
Repeat Pillcam CD (if not done within 6 months)
Repeat IUS +thermal imaging (if not done within 6 months)
MRE
Inclusion Criteria:
Exclusion Criteria: