PROactive and Early Infliximab Monitoring and OPTimization in Inflammatory Bowel Disease
72 patients around the world
Available in Chile
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis
(UC), are chronic diseases that entail important morbidity and frequently require
high-cost medications such as biologic therapies. Monoclonal antibodies against tumoral
necrosis factor (anti-TNF) are effective and can modify the progressive course of IBD. In
Chile, given the high cost of anti-TNF therapy, this medication is provided by a national
program with universal coverage. Unfortunately, a significant proportion of IBD patients
never respond (primary non-response, PNR) or experience loss of response (secondary loss
of response, SLR) to anti-TNF within the first year of therapy and current evidence
support that the complex pharmacokinetics of anti-TNF is involved in both scenarios.
Additionally, low trough levels (TL) are associated with the development of antidrug
antibodies (ADA) which reduce anti-TNF efficacy and can cause anaphylactic reactions.
This is particularly relevant for intravenous infliximab (IFX) which is usually indicated
in IBD patients with acute severe disease not responding to iv corticosteroids.
Therefore, IFX is frequently dose escalated in patients based on clinical parameters that
are thought to be related to drug clearance with conflicting evidence supporting this
strategy. Several studies have demonstrated that IFX TL between 7-20 mcg/ml at week 14 of
treatment is a strong and independent predictor of therapy response. Furthermore, IFX
dashboard-guided dose optimization based on clinical and pharmacokinetic (PK) parameters
using adaptive Bayesian modeling have demonstrated to be more precise that empirical
adjustments based on the clinician intuition alone. Therefore, we will evaluate whether
early therapeutic drug monitoring (TDM) and dose adjustment based on a Bayesian model
(iDOSE) in CD and UC patients initiating IFX, increases the proportion of patients with
therapeutic levels (7-20 mcg/ml), reducing immunogenicity and consequently increasing the
rate of disease remission. We will perform a multicentric randomized clinical trial (RCT)
of Chilean adult IBD inpatients starting IFX due to moderate-to-severe disease refractory
to corticosteroids. Patients will be randomized 1:1 to:
1.
- Dashboard-guided dosing arm. Patients will undergo proactive TDM during
induction (TL at IFN 2 and 3) with dose adjustment based on iDOSE.
2.
- Standard dosing arm. Patients will receive dose adjustment based solely on
clinical parameters.
Both groups will be followed-up after induction with clinical visits, TL and ADA at week
14 (INF 4), 26 and 52. Researchers expect that a higher proportion of patients in the
dashboard-guided dosing arm will achieve therapeutic TL of IFX (7-20 mcg/ml) at week 14
of treatment (Primary outome). Secondary outcomes will include clinical and laboratory
parameters related to therapy response at week 52 of treatment, proportion of patients
experiencing PNR and SLR, patients developing ADA, as well as, adverse events,
hospitalization and surgery
Pontificia Universidad Catolica de Chile
1Research sites
72Patients around the world
This study is for people with
Crohn's disease
Ulcerative colitis
Requirements for the patient
To 75 Years
All Gender
Medical requirements
Adult inpatients with Crohn's disease, ulcerative colitis or inflammatory bowel disease-unclassified.
Moderate-to-severe flare who fail to iv steroids and require infliximab as per standard of care by treating gastroenterologist.
Participant younger than 18 years.
Non-controlled infectious diseases.
Permanent ileostomy or Ileal pouch-anal anastomosis.
Pregnancy.
Patients do not consent to participate in study.
Patients unable to comply with protocol.
Sites
Hospital Clínico Pontificia Universidad Católica de Chile - Santiago, Región Metropolitana