Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab (PRECISION)

Precision Dosing Versus Conventional Dosing of Infliximab Maintenance Therapy: a Randomized Controlled Multicenter Study in Patients With IBD in Clinical Remission

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.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Disease
• Intervention / Treatment: Drug: PRECISION dosing Infliximab

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1102 AZ
      • Academic Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of CD or UC based on endoscopy and pathology
• 18 years or older
• Clinical remission, based on a Harvey Bradshaw Index (HBI) score ≤4 or a Partial Mayo (PM) score ≤2, for CD and UC
• Scheduled IFX maintenance treatment, regardless of interval/dosing

Exclusion Criteria:

- Dilatation or resectional surgery because of stenotic IBD in the past year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRECISION dosing; Infliximab may vary between 1-10 mg/kg and the interval between 4 and 12 weeks.	Drug: PRECISION dosing Infliximab; Patients in the PRECISION dosing arm will recieve model based dosing, whereas proactive adjustments in treatment can be made by measuring the Infliximab concentration.
No Intervention: Conventional dosing of Infliximab; Infliximab 5 mg/kg every 8 or 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained clinical remission for the precision dosing group vs. the conventional IFX maintenance dosing group	Sustained clinical remission based on HBI (Crohn's disease) or PM score (Ulcerative Colitis)	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost of IFX treatment between the two groups	Comparing costs for treatment with IFX between the two groups	52 weeks
Proportion of patients with antibodies against IFX		52 weeks
Quality of life	With a QoL questionnaire	52 weeks
Biochemical disease activity (CRP >5mg/L and fecal calprotectin ≥50% compared to baseline, to a value of >250 ug/g)	A rise in fecal calprotectin of ≥50% compared to baseline, to a value of >250 ug/g and/or serum CRP of >5mg/L	26 weeks, 52 weeks

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Study Director: G D'Haens, Professor gastroenterology

Publications and helpful links

General Publications

• Strik AS, Lowenberg M, Mould DR, Berends SE, Ponsioen CI, van den Brande JMH, Jansen JM, Hoekman DR, Brandse JF, Duijvestein M, Gecse KB, de Vries A, Mathot RA, D'Haens GR. Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients; a randomized controlled trial. Scand J Gastroenterol. 2021 Feb;56(2):145-154. doi: 10.1080/00365521.2020.1856405. Epub 2020 Dec 8.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: April 28, 2015
• First Submitted That Met QC Criteria: May 26, 2015
• First Posted (Estimate): May 27, 2015

Study Record Updates

• Last Update Posted (Actual): August 6, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Remission; IBD; Inflammatory bowel disease; Infliximab; Crohns Disease; Sustained
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: 2014_354