TY  - CHAP
A1  - Steenholdt, Casper
A1  - Edlund, Helena
A1  - Ainsworth, Mark A.
A1  - Brynskov, Jorn
A1  - Thomsen, Ole Ostergaard
A1  - Huisinga, Wilhelm
A1  - Kloft, Charlotte
T1  - Relationship between measures of infliximab exposure and clinical outcome of infliximab intensification at therapeutic failure in Crohn's  disease
T2  - JOURNAL OF CROHNS & COLITIS
Y1  - 2015
SN  - 1873-9946
SN  - 1876-4479
VL  - 9
SP  - S330
EP  - S330
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Edlund, Helena
A1  - Grisic, Ana-Marija
A1  - Steenholdt, Casper
A1  - Ainsworth, Mark Andrew
A1  - Brynskov, Torn
A1  - Huisinga, Wilhelm
A1  - Kloft, Charlotte
T1  - Absence of Relationship Between Crohn's Disease Activity Index or C-Reactive Protein and Infliximab Exposure Calls for Objective Crohn's Disease Activity Measures for the Evaluation of Treatment Effects at Treatment Failure
JF  - Therapeutic drug monitoring : official journal of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology
N2  - Background: Circulating infliximab (IFX) concentrations correlate with clinical outcomes, forming the basis of the IFX concentration monitoring in patients with Crohn's disease. This study aims to investigate and refine the exposure-response relationship by linking the disease activity markers "Crohn's disease activity index" (CDAI) and C-reactive protein (CRP) to IFX exposure. In addition, we aim to explore the correlations between different disease markers and exposure metrics.

Methods: Data from 47 Crohn's disease patients of a randomized controlled trial were analyzed post hoc. All patients had secondary treatment failure at inclusion and had received intensified IFX of 5 mg/kg every 4 weeks for up to 20 weeks. Graphical analyses were performed to explore exposure-response relationships. Metrics of exposure included area under the concentration-time curve (AUC) and trough concentrations (Cmin). Disease activity was measured by CDAI and CRP values, their change from baseline/last visit, and response/remission outcomes at week 12.

Results: Although trends toward lower Cmin and lower AUC in nonresponders were observed, neither CDAI nor CRP showed consistent trends of lower disease activity with higher IFX exposure across the 30 evaluated relationships. As can be expected, Cmin and AUC were strongly correlated with each other. Contrarily, the disease activity markers were only weakly correlated with each other.

Conclusions: No significant relationship between disease activity, as evaluated by CDAI or CRP, and IFX exposure was identified. AUC did not add benefit compared with Cmin. These findings support the continued use of Cmin and call for stringent objective disease activity (bio-)markers (eg, endoscopy) to form the basis of personalized IFX therapy for Crohn's disease patients with IFX treatment failure.
Y1  - 2019
U6  - https://doi.org/10.1097/FTD.0000000000000590
SN  - 0163-4356
SN  - 1536-3694
VL  - 41
IS  - 2
SP  - 235
EP  - 242
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  -