Ultra-proactive Therapeutic Drug Monitoring in Inflammatory Bowel Disease

Study Overview
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Brief Summary
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This is a comparative pragmatic trial in patients with UC and CD on maintenance treatment with IFX. All IBD patients from cohort A with maintenance IFX treatment at a referral IBD clinic are prospectively included between June and August 2018. An ultra-proactive IFX TDM algorithm is applied as follows. All patients have an ELISA TL measurement at baseline, of which the result determined the follow-up pathway: (A) TL between 3-7μg/mL: continuation at same dose and interval; (B) TL >7μg/mL: interval prolongation allowed; (C) TL <3μg/mL: interval shortening with minimum 2 weeks, with the next IFX TL measured using a POCT. (i) If the POCT showed an IFX TL <3μg/mL, dose was optimized ad hoc using a linear dosing formula (Dosen = (TL target * Dose n-1) / TL measured), followed by a new POCT test at next visit with the same interval. (ii) If the POCT showed an IFX TL ≥3µg/mL, no additional dose was given and routine TL testing with ELISA was retaken at next visit. At every visit this algorithm was reapplied to all patients. The patients from cohort A will be compared with the patients from cohort B. The patients in cohort B receive maintenance IFX treatment at a referral IBD clinic during the same period. Dose adjustment are done based on standard of care reactive TDM of IFX and clinical symptoms. Data will be collected retrospectively to avoid treatment optimization bias.

Official Title
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Ultra-proactive Therapeutic Drug Monitoring of Infliximab Based on Point-of-care-testing in Inflammatory Bowel Disease: a Pragmatic Trial

Conditions
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Crohn Disease, Ulcerative Colitis

Intervention / Treatment
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* Biological: infliximab therapeutic drug monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: all adult IBD patients treated for at least 14 weeks with infliximab were included Exclusion Criteria: induction treatment with infliximab (<14 weeks) treatment with other biological for IBD
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: pragmatic cluster trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ultra proactive arm<br> | Biological: infliximab therapeutic drug monitoring<br>* dose optimization of infliximab based on a predefined dosing algorithm<br>|
| Active Comparator: reactive arm<br> | Biological: infliximab therapeutic drug monitoring<br>* dose optimization of infliximab based on a predefined dosing algorithm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients with infliximab failure | number of patients with infliximab failure after one year (infliximab failure = infliximab discontinuation, IBD related surgery, IBD related hospitalization, add-on IBD treatment, and allergic reaction to infliximab) | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of TL measurements per patient per year |  | one year | 
| percentage of interval changes (shortening, prolongation, bidirectional) |  | one year | 
| number of patients with infliximab discontinuation | number of patients with discontinuation of infliximab | one year | 
| percentage of patients with sustained clinical remission | number of patients with physician global assessment <1 and all visits | one year | 
| number of patients with mucosal remission | number of patients with mucosal remission after one year. (Mucosal remission = simple endoscopic score for CD <3, Rutgeertscore <i2 for, Mayo endoscopic subscore <1 and faecal calprotectin <250 µg/ml. Endoscopy and/or faecal calprotectin between 6 and 12 months after inclusion. If endoscopy and faecal calprotectin at the same moment, then endoscopy was dominant) | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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therapeutic drug monitoring, inflammatory bowel disease, point of care testing, infliximab