Original articleAlimentary tractPharmacokinetic Features and Presence of Antidrug Antibodies Associate With Response to Infliximab Induction Therapy in Patients With Moderate to Severe Ulcerative Colitis
Section snippets
Methods
This prospective cohort study was performed at 2 centers in Amsterdam, The Netherlands (an academic referral center, the Academic Medical Center, and a regional teaching hospital, Onze Lieve Vrouwe Gasthuis), between 2012 and 2014. Consecutive anti-TNF–naive adults with moderate-to-severe UC (endoscopic Mayo score, 2 or 3) were included after providing informed consent. Infliximab was administered intravenously at a dose of 5 mg/kg, either during admission or at the outpatient infusion clinic.
Results
Twenty consecutive UC patients were included. All but 1 patient suffered from severe Mayo 3 colitis at baseline endoscopy and one third of patients were hospitalized at initiation of IFX therapy (Table 1). Eleven patients were on concomitant steroids (40 mg, 7 intravenous and 4 oral).
Discussion
In this intensive pharmacokinetic study we observed that antidrug antibodies already appear during induction treatment, impair IFX drug concentrations, and predict nonresponse in patients with moderate-severe UC. Furthermore, high baseline CRP levels had a strong negative impact on serum IFX concentrations in UC patients receiving conventional IFX induction therapy. In addition to baseline CRP, low serum albumin levels and extensive colitis correlated with lower serum IFX concentrations and a
References (27)
- et al.
Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn's disease
Clin Gastroenterol Hepatol
(2006) - et al.
Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial
Lancet
(2012) - et al.
Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis
Gastroenterology
(2014) - et al.
Development and validation of a homogeneous mobility shift assay for the measurement of infliximab and antibodies-to-infliximab levels in patient serum
J Immunol Methods
(2012) - et al.
Immune complex size and complement regulate cytokine production by peripheral blood mononuclear cells
Clin Immunol
(1999) - et al.
Infliximab for induction and maintenance therapy for ulcerative colitis
N Engl J Med
(2005) - et al.
Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease
N Engl J Med
(2003) - et al.
Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis
Gut
(2010) - et al.
Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis
Eur J Clin Pharmacol
(2009) - Kevans D, Murthy S, Iacono A, et al. Sa2031 accelerated clearance of serum infliximab during induction therapy for...
Loss of infliximab into feces is associated with lack of response to therapy in patients with severe ulcerative colitis
Gastroenterology
An accelerated infliximab induction regimen reduces the need for early colectomy in patients with acute severe ulcerative colitis
Clin Gastroenterol Hepatol
A simple clinical colitis activity index
Gut
Cited by (161)
Medical treatment of ulcerative colitis
2022, Seminars in Colon and Rectal SurgeryCitation Excerpt :Patients receiving azathioprine in addition to infliximab also had lower levels of serum anti-drug antibodies than those receiving infliximab alone. The presence of anti-drug antibodies leads to increased anti-TNF antagonist clearance which is associated with diminished therapeutic response.9 Thioguanine nucleotides (TGN) are active metabolites of azathioprine and 6-mercaptopurine.7
Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives
2022, The Lancet Gastroenterology and HepatologyCitation Excerpt :Furthermore, preliminary data suggest that proactive TDM might be associated with better therapeutic outcomes than empiric dose optimisation and reactive TDM.5–13 In addition, numerous exposure–outcome relationship data both in IBD (table 1)14–53 and other IMIDs including rheumatoid arthritis and psoriasis (appendix pp 1–3), from retrospective and prospective studies and post-hoc analyses of randomised controlled trials (RCTs), show that high drug concentrations are associated with improved therapeutic outcomes.14–91 Conversely, lower drug concentrations, with or without ADAs, are associated with treatment failure and drug discontinuation.2,3
Performance of a New Rapid Point-of-Care Test for Infliximab Levels in Patients with Inflammatory Bowel Disease: A Comparison to ELISA
2024, Digestive Diseases and SciencesA review article of inflammatory bowel disease treatment and pharmacogenomics
2023, Beni-Suef University Journal of Basic and Applied Sciences
Conflicts of interest These authors disclose the following: Johannan Brandse has received lecture fees from MSD and Takeda; Ron Mathôt has received consulting fees from Merck Sharp & Dohme and research grants from Bayer, UCB Pharma, and Hoffmann La Roche; Desiree van der Kleij is the Head of the Biologicals Laboratory of Sanquin Diagnostic Services, which performs assays for biological levels and antidrug antibodies for many pharmaceutical industries and hospitals; Theo Rispens has received honoraria for lectures from Pfizer and AbbVie; Jeroen Jansen has served as a speaker for Merck Sharp & Dohme and Abbvie and has served as a consultant for Ferring Pharmaceuticals, Schering Plough, AbbVie, and Pfizer; Mark Löwenberg has served as speaker and/or principal investigator for AbbVie, Covidien, Dr. Falk, Ferring Pharmaceuticals, Merck Sharp & Dohme, Receptos, Takeda, and Tramedico, and has received research grants from AbbVie, Merck Sharp & Dohme, and Achmea Healthcare; Cyriel Ponsioen has served as a speaker for Schering Plough, Falk Pharma, Tramedico, Abbott, Inc, and Glaxo Smith Kline, has served as a consultant for Schering Plough, Falk Pharma, Tramedico, Abbott, Inc, and Glaxo Smith Kline, and has received research funding from Schering Plough, Falk Pharma, Tramedico, Abbott, Inc, and Glaxo Smith Kline; Sharat Singh worked for Prometheus Laboratories; Gijs van den Brink has received consulting fees from Abbott Laboratories, and lecture fees from Abbott Laboratories, Merck Sharp & Dohme, and Ferring Pharmaceuticals, and has received research grants from Abbott Laboratories, Crucell, and Ferring Pharmaceuticals; and Geert D’Haens has served as a speaker for AbbVie, Ferring, Jansen Biologics, Merck Sharp Dome, Mundipharma, Norgine, Shire, Takeda, Tillotts, UCB, and Vifor, and has served as an advisor for AbbVie, Ablynx, Actogenix, Amakem, Amgen, AM Pharma, AstraZeneca, Avaxia, Bristol Meiers Squibb, Boerhinger Ingelheim, Celgene, Celltrion, Cosmo, Covidien, Elan, Ferring, Dr Falk Pharma, Centocor/Jansen Biologics, Engene, Ferring, Galapagos, Gilead, Glaxo Smith Kline, Hospira, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Novonordisk, Otsuka, Pfizer, Protein Design Laboratories, Prometheus Laboratories/Nestle, Receptos, Robarts Clinical Trials, Salix, Sandoz, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, UCB, Versant, and Vifor. The remaining authors disclose no conflicts.
Funding This investigator-initiated study was self-funded. Antidrug antibody assessment was supported by Prometheus Laboratories.