Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab
Condition: Inflammatory Bowel Disease
MeSH terms: Intestinal Diseases; Inflammatory Bowel Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      Infliximab (IFX) is highly effective in inducing and maintaining remission in patients with
      inflammatory bowel disease (IBD). However, a large proportion of patients will eventually
      lose response to IFX. Therefore, strategies to improve the outcome of maintenance treatment
      with IFX are required. Retrospective analyses suggest that adjusting IFX treatment in order
      to achieve IFX trough levels (TL) above a well-defined therapeutic threshold will improve the
      outcome of IFX treatment.
    

Detailed description: 
      Aim of this study is to investigate the efficacy of "precision dosing" IFX maintenance
      treatment in comparison with standard IFX maintenance treatment in IBD patients in clinical
      remission.

      This study will be an open, randomized, controlled trial. Inclusion criteria: Patients aged
      ≥18 years with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) based on
      endoscopy and pathology, receiving scheduled IFX therapy for ≥14 weeks, in clinical remission
      based on a Harvey Bradshaw Index (HBI) score ≤4 or a Partial Mayo (PM) score ≤2, for CD and
      UC, respectively. Exclusion criteria: Dilatation or resectional surgury in the past year and
      patients with a stoma/pouch.

      Patients in the intervention arm will receive individualized treatment with variable IFX
      dosing AND/OR intervals guided by a Bayesian pharmacokinetic model, aiming to achieve an IFX
      TL of 3 µg/ml. Patients in the control group will continue to receive the same IFX treatment
      regimen that was given prior to inclusion without dose adaptation. In the control group,
      treatment adjustments will only be made in case of signs of active disease, in accordance to
      current routine care but these patients will be considered as failures to their treatment.

      Primary endpoint: Proportion of patients with sustained clinical remission (based on HBI or
      PM). Secondary endpoints include: annual costs of IFX treatment per patient, total annual
      medical costs, side effects, (sustained) biochemical remission, adverse events, quality of
      life, IFX trough level and IFX antibodies (with an assay allowing presence of drug).

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: Participation will result in additional blood sampling, since IFX serum
      concentration will be measured every 8 weeks. All other laboratory tests can be considered as
      routine care. Patients in the intervention group with IFX TLs >3 will receive treatment
      de-escalation (interval elongation and/or dose reduction) as indicated by the Baysian model.
      Current evidence indicates that an IFX TL of 3 suffices. Patients in the intervention group
      with TLs <3 will receive treatment escalation (interval shortening and/or dose increase). We
      hypothesize that this will result in a higher chance of remaining in clinical remission.
    

Intervention name(s): PRECISION dosing Infliximab
Intervention type(s): Drug
Intervention description(s): Patients in the PRECISION dosing arm will recieve model based dosing, whereas proactive adjustments in treatment can be made by measuring the Infliximab concentration.
Intervention MeSH terms: Infliximab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Crohns Disease; Ulcerative Colitis; Infliximab; Sustained; Remission; Inflammatory bowel disease; IBD