Model-informed Dose De-escalation of Infliximab in Patients With Inflammatory Bowel Diseases

Study Overview
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Brief Summary
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This is a monocentric, two-arm, non-randomised, non-blinded, historically controlled, interventional trial. The purpose of this trial is to investigate the effect of model-informed infliximab dose de-escalation on the infliximab exposure and therapeutic outcome as compared to standard dose de-escalation in patients with inflammatory bowel diseases.

Official Title
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Model-informed Infliximab Dose De-escalation Following Earlier Dose Escalation in Adult Patients With Inflammatory Bowel Diseases

Conditions
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Inflammatory Bowel Diseases

Intervention / Treatment
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* Drug: Infliximab
* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject or, when applicable, the subject's legally acceptable representative signs and dates a written informed consent form and any required privacy authorisation prior to the initiation of any study procedures. The subject is aged 18 to 80 years inclusive. The subject has a good understanding of the Dutch language. The subject is diagnosed with moderately to severely active ulcerative colitis or Crohn's disease, confirmed by clinical, endoscopic, histological, and/or imaging criteria. The subject was in maintenance therapy, later lost their response to treatment and subsequently gained steroid-free, clinical and biological remission following infliximab dose escalation (i.e., by increasing the dose and/or shortening the dosing interval) and had an infliximab trough concentration ≥5 mg/L. Adequate contraception in female subjects of reproductive age (oral contraception, intra-uterine device, sterilisation or barrier method). Exclusion Criteria: The subject is aged <18 years or >80 years. The subject receives infliximab prophylactically (e.g. in the immediate postoperative setting). The subject has an ostomy or an ileal anal pouch anastomosis. If female subjects, when pregnant (based on a positive serum sample) or lactating or intending to become pregnant or nurse before, during or within 15 weeks after the last dose of study drug; or intending to donate ova during such time period. The subject is participating in another interventional clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional arm<br>Model-informed precision dosing of infliximab (intravenously administered) using a Bayesian forecasting software tool. Doses and dosing intervals will be derived from the software tool, aiming to maintain adequate exposure (trough concentration target 5 mg/L). | Drug: Infliximab<br>* Infliximab (Inflectra® [Pfizer]), dosage determined using model-informed precision dosing, intravenously administered<br>|
| Active Comparator: Historical control arm<br>The treating physician adjusted the intravenously administered infliximab doses and dosing intervals without being guided by a model-informed precision dosing software tool. The primary objective was to extend the dosing interval. Therefore, dose de-escalation (interval extension with/without dose adjustment) were performed following a scheme at the treating physician's discretion. | Drug: Infliximab<br>* Infliximab, dosage following a dose de-escalation algorithm at the physician's discretion, intravenously administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steroid-free, combined clinical and biological remission | The proportion of patients maintaining steroid-free, combined clinical and biological remission during one year after infliximab dose de-escalation based on a standard dosing algorithm versus a model-informed dosing algorithm. Combined clinical and biological remission is defined based on patient-reported outcomes (rectal bleeding score = 0 + stool frequency score ≤1 [ulcerative colitis], mean daily abdominal pain score ≤1 + liquid stool frequency score ≤1.5 [Crohn's disease]) together with normal C-reactive protein (<5 mg/L) and faecal calprotectin (<250 mg/kg). Steroid-free indicates the absence of any dose of any oral or rectal steroid use. | During one year after start of infliximab dose de-escalation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steroid-free, combined clinical and biological remission | The proportion of patients maintaining steroid-free, combined clinical and biological remission at one year after infliximab dose de-escalation based on a standard dosing algorithm versus a model-informed dosing algorithm. Combined clinical and biological remission is defined based on patient-reported outcomes (rectal bleeding score = 0 + stool frequency score ≤1 [ulcerative colitis], mean daily abdominal pain score ≤1 + liquid stool frequency score ≤1.5 [Crohn's disease]) together with normal C-reactive protein (<5 mg/L) and faecal calprotectin (<250 mg/kg). Steroid-free indicates the absence of any dose of any oral or rectal steroid use. | At one year after start of infliximab dose de-escalation |