MODIFI: Model-informed Dose De-escalation of Infliximab in Patients With Inflammatory Bowel Diseases
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Interventional arm 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
Infliximab (Inflectra® [Pfizer]), dosage determined using model-informed precision dosing, intravenously administered
|
| Active Comparator: Historical control arm 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
Infliximab, dosage following a dose de-escalation algorithm at the physician's discretion, intravenously administered
|
Outcome Measures
Primary Outcome Measures
- Steroid-free, combined clinical and biological remission [During one year after start of infliximab dose de-escalation]
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.
Secondary Outcome Measures
- Steroid-free, combined clinical and biological remission [At one year after start of infliximab dose de-escalation]
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.
Other Outcome Measures
- Steroid-free clinical remission [At and during one year after start of infliximab dose de-escalation]
The proportion of patients maintaining steroid-free clinical remission at and during one year after infliximab dose de-escalation based on a standard dosing algorithm versus a model-informed dosing algorithm. Clinical 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]). Steroid-free indicates the absence of any dose of any oral or rectal steroid use.
- Steroid-free biological remission [At and during one year after start of infliximab dose de-escalation]
The proportion of patients maintaining steroid-free biological remission at and during one year after infliximab dose de-escalation based on a standard dosing algorithm versus a model-informed dosing algorithm. Biological remission is defined as 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.
- Infliximab trough concentration target attainment and area under the concentration-time curve [At and during one year after start of infliximab dose de-escalation]
Exposure: Trough concentration (target attainment; 5 mg/L) and area under the concentration-time curve.
- Total infliximab dose and number of infusions [At and during one year after start of infliximab dose de-escalation]
Dosage: total infliximab dose (# mg) and number of infusions.
- Direct costs calculated based on cost of infliximab and cost related to the day hospital needed for the infusion [At one year after start of infliximab dose de-escalation]
Direct costs calculated based on cost of infliximab and cost related to the day hospital needed for the infusion (in euro).
- Indirect costs based on questionnaire [At one year after start of infliximab dose de-escalation]
Indirect costs based on questionnaire: iMTA Productivity Cost Questionnaire (iMTA PCQ)
- Health-related quality of life based on QoL questionnaire [At one year after start of infliximab dose de-escalation]
Health-related quality of life based on QoL questionnaire: Inflammatory Bowel Disease Questionnaire (IBDQ-32)
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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The subject is aged 18 to 80 years inclusive.
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The subject has a good understanding of the Dutch language.
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The subject is diagnosed with moderately to severely active ulcerative colitis or Crohn's disease, confirmed by clinical, endoscopic, histological, and/or imaging criteria.
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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.
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Adequate contraception in female subjects of reproductive age (oral contraception, intra-uterine device, sterilisation or barrier method).
Exclusion Criteria:
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The subject is aged <18 years or >80 years.
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The subject receives infliximab prophylactically (e.g. in the immediate postoperative setting).
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The subject has an ostomy or an ileal anal pouch anastomosis.
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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.
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The subject is participating in another interventional clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UZ Leuven | Leuven | Vlaanderen | Belgium | 3000 |
Sponsors and Collaborators
- Universitaire Ziekenhuizen Leuven
- KU Leuven
Investigators
- Principal Investigator: Marc Ferrante, MD, PhD, UZ Leuven
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- S64521