Original articleAlimentary tractLevels of Drug and Antidrug Antibodies Are Associated With Outcome of Interventions After Loss of Response to Infliximab or Adalimumab
Section snippets
Patients
This was a multicenter retrospective cohort study. All inflammatory bowel disease (IBD) patients with serum samples analyzed for adalimumab or infliximab drug and ADA TLs at the time of suspected LOR between October 2009 and February 2013 were identified. Tests for primary nonresponse, infusion reactions, or tests that were not obtained at trough were excluded. This study was centrally approved by the Institutional Review Board of the Sheba Medical Center and by the ethics committees of the
Results
Of 303 patients with available sera tested for drug/ADA levels, 247 patients were eligible for inclusion (199 Crohn's disease, 42 ulcerative colitis, and 6 IBD-unclassified patients). The clinical characteristics of the study population are shown in Table 1. Overall, 180 of 247 patients had a single serum sample analyzed for drug/ADA TLs because of a clinically suspected LOR event, 47 patients had 2 suspected LOR events for which serum analysis was performed, 16 patients had 3 events, and 2
Discussion
Despite the proven efficacy of anti-TNF agents in IBD, LOR remains a common clinical problem, posing both evaluation and management dilemmas pertaining to the decision regarding the most appropriate intervention. Several TDM algorithms using drug/ADA levels have been proposed for the management of LOR.11, 12, 13, 14, 20 In a recent trial, patients with suspected LOR who were treated by a TDM-based strategy fared clinically similar but at significantly reduced costs compared with empiric
References (28)
- et al.
Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn's disease
Clin Gastroenterol Hepatol
(2004) - et al.
Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn's disease
Gastroenterology
(2009) - et al.
Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn's disease
Clin Gastroenterol Hepatol
(2006) - 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.
Therapeutic drug monitoring of tumor necrosis factor antagonists in inflammatory bowel disease
Clin Gastroenterol Hepatol
(2012) - et al.
Association between pharmacokinetics of adalimumab and mucosal healing in patients with inflammatory bowel diseases
Clin Gastroenterol Hepatol
(2014) - et al.
Review article: loss of response to anti-TNF treatments in Crohn's disease
Aliment Pharmacol Ther
(2011) - et al.
Loss of response and need for adalimumab dose intensification in Crohn's disease: a systematic review
Am J Gastroenterol
(2011) - et al.
Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review
Am J Gastroenterol
(2009) - et al.
Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease
Am J Gastroenterol
(2008)
Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease
N Engl J Med
The immunogenic part of infliximab is the F(ab')2, but measuring antibodies to the intact infliximab molecule is more clinically useful
Gut
Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis
Gut
Therapeutic drug monitoring of biologics for inflammatory bowel disease
Inflamm Bowel Dis
Cited by (261)
Successful ligelizumab treatment of severe refractory solar urticaria
2023, Journal of Allergy and Clinical Immunology: In PracticeControversies in the management of anti-TNF therapy in patients with Crohn's disease: a Delphi consensus
2024, BMJ Open GastroenterologyAnti-drug antibodies against anti-TNF in patients with inflammatory bowel disease: an evaluation of possible strategies
2024, Scandinavian Journal of Gastroenterology
Conflicts of interest These authors disclose the following: Shomron Ben-Horin, Yehuda Chowers, and Rami Eliakim have received consulting fees from Abbott, Janssen, and Schering-Plough; Shomron Ben-Horin and Yehuda Chowers have received an unrestricted educational grant from Janssen; Arie Levine has received unrestricted educational grants or speaker fees from Jannsen, Nestle, Abbot, and MSD; and Iris Dotan has received consultancy fees from Abbott, Janssen, and Schering-Plough, and has received research grants from Abbott and Schering-Plough. The remaining authors disclose no conflicts.
Funding Supported in part by the Talpiot medical leadership grant from the Sheba Medical Center (S.B.-H.), by the Legacy Heritage Foundation from the Rambam Health Care Center (Y.C.), and by the Leona M. and Harry B. Helmsley Charitable Trust (I.D., R.E., S.B.-H., and Y.C.).
- b
Authors share co-senior authorship.