TY  - GEN
A1  - Grisic, Ana-Marija
A1  - Huisinga, Wilhelm
A1  - Reinisch, W.
A1  - Kloft, Charlotte
T1  - P485 Dosing infliximab in Crohn's disease
BT  - is adjustment for body size justified?
T2  - Journal of Crohn's and Colitis
N2  - Background: Infliximab (IFX), an anti-TNF monoclonal antibody approved for the treatment of inflammatory bowel disease, is dosed per kg body weight (BW). However, the rationale for body size adjustment has not been unequivocally demonstrated [1], and first attempts to improve IFX therapy have been undertaken [2]. The aim of our study was to assess the impact of different dosing strategies (i.e. body size-adjusted and fixed dosing) on drug exposure and pharmacokinetic (PK) target attainment. For this purpose, a comprehensive simulation study was performed, using patient characteristics (n=116) from an in-house clinical database.

Methods: IFX concentration-time profiles of 1000 virtual, clinically representative patients were generated using a previously published PK model for IFX in patients with Crohn's disease [3]. For each patient 1000 profiles accounting for PK variability were considered. The IFX exposure during maintenance treatment after the following dosing strategies was compared: i) fixed dose, and per ii) BW, iii) lean BW (LBW), iv) body surface area (BSA), v) height (HT), vi) body mass index (BMI) and vii) fat-free mass (FFM)). For each dosing strategy the variability in maximum concentration Cmax, minimum concentration Cmin (= C8weeks) and area under the concentration-time curve (AUC), as well as percent of patients achieving the PK target, Cmin=3 μg/mL [4] were assessed.

Results: For all dosing strategies the variability of Cmin (CV ≈110%) was highest, compared to Cmax and AUC, and was of similar extent regardless of dosing strategy. The proportion of patients reaching the PK target (≈⅓ was approximately equal for all dosing strategies.
Y1  - 2017
U6  - https://doi.org/10.1093/ecco-jcc/jjx002.609
SN  - 1873-9946
SN  - 1876-4479
VL  - 11
IS  - 1
SP  - S325
EP  - S326
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - CHAP
A1  - Andersson, H.
A1  - Keunecke, A.
A1  - Eser, A.
A1  - Huisinga, Wilhelm
A1  - Reinisch, W.
A1  - Kloft, Charlotte
T1  - Pharmacokinetic considerations for optimising dosing regimens of  a potsdam univ infliximab in patients with Crohn's disease
T2  - JOURNAL OF CROHNS & COLITIS
Y1  - 2014
U6  - https://doi.org/10.1016/S1873-9946(14)60086-6
SN  - 1873-9946
SN  - 1876-4479
VL  - 8
SP  - S44
EP  - S44
PB  - Oxford Univ. Press
CY  - Oxford
ER  -