The aim of this study is to investigate whether intensive, personalized IFX dosing by using a pharmacokinetics driven dashboard system during the induction phase in patients with acute severe UC leads to increased treatment success (as defined by clinical and endoscopic response at week 6) as compared to the standard dosing.
Previous studies performed in the AMC demonstrated that the patients with acute severe UC receiving IFX are different from patients receiving IFX while in remission.(5) The clearance of IFX is not only determined by demographic parameters (gender, body weight), blood chemistry (CRP, albumin) and anti-drug antibodies, but also disease related variables play an important role. Among others, we have demonstrated that faecal loss of IFX in ASUC patients increases IFX clearance during the induction phase (3). Furthermore, increased expression of TNF-α, the target of IFX, influences the clearance of IFX due to target mediated drug disposition (TMDD). Active IBD with high tissue concentrations of TNF-α thereby acts as a sink for anti-TNF-α antibodies (4). The PK of IFX has been mainly characterized during maintenance therapy. Evaluation of factors that influence the clearance of IFX during induction therapy will allow further optimization an individualization of IFX therapy in ASUC patients. At present, determination of IFX concentrations in the serum with an enzyme-linked immunosorbent assay (ELISA) is time consuming; physicians often receive the results after as many as 10-20 days. To allow for proactive adjustments in dosing, faster laboratory results are required, preferably in a point-of-care setting. This test is now made available by Bühlmann Laboratories (Switzerland). The study hypothesis is that in patients with acute severe UC an intensified and personalized IFX dosing regimen using individual PK data from point of care tests as a rapid input to the dashboard system during the induction phase will lead to improved clinical outcomes when compared to standard dosing regimen.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
infliximab iv 5mg/kg
St Vincent's University Hospital
Dublin, Ireland
Academic Medical Center
Amsterdam, Netherlands
OLVG Oost
Amsterdam, Netherlands
Radboud UMC
Nijmegen, Netherlands
Increased treatment success
Defined by clinical and endoscopic reponse. Clinical response defined as a Lichtiger score of less than 10 points with a decrease of at least 3 points compared to baseline. Endoscopic response is defined as a decrease of at least 2 points in the UCEIS at week 6 endoscopy compared to baseline
Time frame: week 6
Endoscopic Remission
Mayo score 2 or less with no individual subscore less than 1
Time frame: week 6 and week 26
Endoscopic Reponse
Decrease in Mayo score of 3 or more points and a 30% or more from baseline and a decrease in rectal bleeding score of 1 or more or an absolute rectal bleeding score of 0 or 1
Time frame: week 6 and week 26
Clinical Remission
Measured by the Simple Clinical Colitis Activity Index (SCCAI score ≤ 2)
Time frame: Week 6 and week 26
Corticosteroid-free remission
Measured by the Simple Clinical Colitis Activity Index (SCCAI score ≤ 2)
Time frame: week 26
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Klinikk Baerum Sykehus
Bærums verk, Norway
Akerhus University Hospital
Lørenskog, Norway
Helse Stavanger
Stavanger, Norway