Original ResearchFull Report: Clinical—Alimentary TractTrough Concentrations of Infliximab Guide Dosing for Patients With Inflammatory Bowel Disease
Section snippets
Design Overview
This randomized controlled trial was conducted at the University Hospitals Leuven, an academic and tertiary referral center from August 2011 to April 2013. The protocol was approved by the Institutional Review Board (ClinicalTrialsRegister.eu number, 2011-002061-38). All patients provided written informed consent.
Setting and Participants
Eligibility criteria included age of at least 18 years and a diagnosis of moderate-to-severe CD or UC confirmed by endoscopy and histology. Patients needed to be treated with
Screening
A consecutive cohort of 275 IBD patients (186 CD and 89 UC) receiving maintenance infliximab were screened from August through October 2011. Overall median CRP was 1.8 mg/L (IQR, 0.7–4.8 mg/L) and median infliximab TC was 4.6 μg/mL (IQR, 2.4–7.3 μg/mL). Of 275 patients, the infliximab TC was >7 μg/mL in 72 patients (26.2%); between 3 and 7 μg/mL in 121 patients (44.0%); detectable but <3 μg/mL in 58 patients (21.1%); and undetectable in 24 patients (8.7%). Of the 24 patients with an
Discussion
Fewer than half of the patients treated with maintenance infliximab had optimal infliximab TCs. Dose escalation in CD patients with a suboptimal infliximab TC led to a significant increase in patients in clinical remission and a concomitant significant drop in CRP concentrations. A similar effect was not seen for UC patients, most likely because the majority had a PMS of 0 and a normal CRP at baseline. Dose reduction in CD and UC patients with a supra-optimal infliximab TC did not lead to
Acknowledgments
The authors are grateful to the patients who were willing to participate in this study and for their support in the research on IBD. The authors are indebted to the IBD nurses at the infusion unit: Ingrid De Wolf, Marie-Josee Vermeyen, Anita Vleminckx, and Ellen Weyts for their professionalism, help, and involvement. Karolien Claes for her help with serum sample collection, Sophie Tops and Miet Peeters for their help with analyzing serum drug and anti-drug antibody concentrations, and Sarah
References (29)
- et al.
Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial
Lancet
(2002) - et al.
Comparison of scheduled and episodic treatment strategies of infliximab in Crohn's disease
Gastroenterology
(2004) - et al.
Pharmacokinetic properties of infliximab in children and adults with Crohn's disease: a retrospective analysis of data from 2 phase III clinical trials
Clin Ther
(2011) - et al.
Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease
Clin Gastroenterol Hepatol
(2006) - et al.
Infliximab trough levels may predict sustained response to infliximab in patients with Crohn's disease
J Crohns Colitis
(2013) - et al.
Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: definitions, frequency and pharmacological aspects
J Crohns Colitis
(2010) - et al.
Withdrawal of immunosuppression in Crohn's disease treated with scheduled infliximab maintenance: a randomized trial
Gastroenterology
(2008) - et al.
Infliximab for induction and maintenance therapy for ulcerative colitis
N Engl J Med
(2005) - et al.
Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review
Am J Gastroenterol
(2009) - et al.
A panel to predict long-term outcome of infliximab therapy for patients with ulcerative colitis
Clin Gastroenterol Hepatol
(2015)
Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis
Eur J Clin Pharmacol
Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease
N Engl J Med
Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis
Gut
Association between serum concentration of infliximab and efficacy in adult patients with ulcerative Colitis
Gastroenterology
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This article has an accompanying continuing medical education activity on page e13. Learning Objective: Upon completion of this exam, successful learners will be able to discuss the impact of dose escalation of infliximab in Crohn's disease patients with low troughs; identify patients where dose reduction is appropriate based on symptoms, trough concentrations, and inflammatory markers; and review timing and frequency of testing for anti-infliximab antibody testing.
Conflicts of interest These authors disclose the following: Niels Vande Casteele reports consultancy fees from MSD, Janssen Biologics, UCB, and speaker’s fees from Abbvie, outside the submitted work. Marc Ferrante reports consultancy fees from Abbvie, Merck, Janssen Biologics, grants from Janssen Biologics, and speaker’s fees from Merck, Tillots, Ferring, Abbvie, outside the submitted work. Gert Van Assche reports consultancy fees from Zealand Pharma, Shire, Abbott/Abbvie, Novartis, MSD, Janssen, BMS, Ferring, Chiesi, Takeda, grants from MSD, Abbott/Abbvie, Zealand Pharma, and speaker’s fees from Janssen, Abbott/Abbvie, Ferring, Aptalis, Ferring, MSD, outside the submitted work; Vera Ballet has nothing to disclose; Griet Compernolle has nothing to disclose. Paul Rutgeerts reports consultancy fees from Amgen, Merck, UCB Pharma, Genentech, BMS, Abbvie, Janssen Biologics, Millennium, Neovacs, Actogenics, Prometheus Laboratories, Inc., grants from UCB Pharma, Abbvie, Janssen Biologics, Merck, Prometheus Laboratories, Inc., and speaker’s fees from Abbvie, Merck, outside the submitted work. Ann Gils reports grants from Pfizer, and speaker’s fees from MSD, Janssen Biologicals, Pfizer, outside the submitted work. Séverine Vermeire reports consultancy fees from Takeda, Roche/Genentech, Merck, Centocor, Abbvie, UCB, Pfizer, Ferring, grants from Centocor, Abbvie, Merck, and speaker’s fees from Merck, Abbvie, Takeda, Pfizer, Ferring, Falk, Centocor, outside the submitted work. The remaining authors disclose no conflicts.
Funding This study was funded in part by the Research Foundation–Flanders (FWO), Belgium; grant number G061712 and Niels Vande Casteele is a Postdoctoral Fellow of the Research Foundation–Flanders (FWO), Belgium; grant number 1260714N. There was no external funding source that had an involvement on any aspect pertinent to the study.
Author names in bold designate shared co-first authorship.
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Authors share co-senior authorship.