Inflammatory Bowel Diseases
Conditions
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.
Interventions
DRUGInfliximab
Infliximab (Inflectra® \[Pfizer\]), dosage determined using model-informed precision dosing, intravenously administered
Sponsors
KU Leuven
Universitaire Ziekenhuizen KU Leuven
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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) |
| 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). |
| 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. |
Countries
Belgium
Outcome results
None listed