Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease

Authors


  • Supported by unrestricted grants from Aase and Ejnar Danielsen's Foundation, Beckett Foundation, Danish Biotechnology Program, Danish Colitis-Crohn Society, Danish Medical Association Research Foundation, Frode V. Nyegaard and wife's Foundation, Health Science Research Foundation of Region of Copenhagen, Herlev Hospital Research Council, Lundbeck Foundation, and P. Carl Petersens Foundation.

  • Presented orally at UEGW in October 2011: Steenholdt C, Al-khalaf M, Bendtzen K, Thomsen OØ, Brynskov J, Ainsworth MA. Kinetics and clinical implications of anti-infliximab antibodies in patients with inflammatory bowel disease. Oral presentation OP220 UEGW (SE; 2011). Gut 2011;60(Suppl 3):A51.

Abstract

Background:

The aim of the study was to investigate variations in anti-infliximab (IFX) antibody (Ab) levels and clinical implications thereof in patients with inflammatory bowel disease (IBD).

Methods:

A retrospective, explorative, single-center study of patients with IBD who developed anti-IFX Ab and in whom anti-IFX Ab were reassessed.

Results:

IFX was administered to 316 patients; anti-IFX Ab was determined in 180 patients and detected in 83 (46%). During ongoing IFX maintenance therapy, anti-IFX Ab disappeared at later reassessment in two-thirds of patients with clinical response after median 4 (3–5) infusions. In contrast, anti-IFX Ab persisted in all patients without clinical response. Anti-IFX Ab appeared pharmacologically active, as IFX levels were high when anti-IFX Ab disappeared (median 3.7 μg/mL, interquartile range [IQR] 2.8–5.5), while undetectable or low when anti-IFX Ab persisted (median 0 μg/mL, IQR 0–0). In 56 patients, anti-IFX Ab were assessed after IFX discontinuation. The proportion of patients with anti-IFX Ab gradually declined over time, with a few patients having anti-IFX Ab up to about 4 years after initial assessment. No variables were associated with anti-IFX Ab disappearance in multivariate analysis.

Conclusions:

Discontinuation of IFX is advisable in patients with inadequate response and repeat positive anti-IFX Ab measurements. Anti-IFX Ab can persist for years after discontinuation, which could impact efficacy and safety at retreatment. Continued IFX treatment may, however, be considered in patients with clinical response and a single positive anti-IFX Ab measurement, as anti-IFX Ab disappears in two-thirds of these during continued treatment. (Inflamm Bowel Dis 2012;)

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