Biologic concentration testing in inflammatory bowel disease

Abstract

Anti-TNF medications have revolutionized the care of patients with inflammatory bowel disease. However, despite an initial robust effect, loss of response is common and long-term results are disappointing. Much of this lack of durability may be due to inadequate dose optimization, and recent studies suggest a correlation between serum drug concentrations and clinical outcomes. Currently, in clinical practice, measurement of drug concentrations and antibodies to drug are typically performed only when a patient presents with active inflammatory bowel disease symptoms or during a potential immune-mediated reaction to anti-TNF ("reactive" setting). However, proactive monitoring of anti-TNF concentrations with titration to a therapeutic window (i.e., therapeutic concentration monitoring) represents a new strategy with many potential clinical benefits including prevention of immunogenicity, less need for IFX rescue therapy, and greater durability of IFX treatment. This review will cover the salient features of anti-TNF pharmacokinetics and pharmacodynamics and provide a rational approach for the use of anti-TNF concentration testing in both the reactive and proactive settings.

FIGURE 1

Clinical algorithm for using reactive IFX concentration and antibody status to guide therapy decisions. *Exact upper and lower limit are unknown. The authors suggest a therapeutic concentration to be 5 to 10 µg/mL, whereas a low concentration is <5 µg/mL. IMM: Immunomodulator.

FIGURE 2

A, Probability of continuing on IFX among patients who had proactive TCM of IFX through trough concentration monitoring versus control group of patients treated with standard of care (HR, 0.3; 95% CI, 0.1–0.6; log rank test; P = 0.0006). B, Probability of continuing IFX based on trough concentration. Log rank test for IFX trough ≥5 µg/mL (at any point in therapy) versus never achieving an IFX trough <5 mg/mL, P < 0.0001 (HR: 0.03; 95% CI, 0.001–0.1). Log rank test for IFX trough ≥5 µg/mL versus no trough testing, P < 0.0001 (HR: 0.2; 95% CI. 0.07–0.4). Log rank test for IFX trough <5 µg/mL (at any point in therapy) versus no trough testing, P = 0.6 (HR: 1.3; 95% CI, 0.5–3.3). Adapted from Vaughn et al. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.”

FIGURE 3

Clinical algorithm for using proactive TCM of IFX trough concentrations for dosing and management of IFX. *High, low, and therapeutic concentrations are not exactly known. The authors suggest that > 10 µg/mL is high, whereas less than 5 µg/mL is low.