P485 Dosing infliximab in Crohn's disease
- 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 BWBackground: 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.…
Verfasserangaben: | Ana-Marija GrisicORCiDGND, Wilhelm HuisingaORCiDGND, W. Reinisch, Charlotte KloftORCiDGND |
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DOI: | https://doi.org/10.1093/ecco-jcc/jjx002.609 |
ISSN: | 1873-9946 |
ISSN: | 1876-4479 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/28172668 |
Titel des übergeordneten Werks (Englisch): | Journal of Crohn's and Colitis |
Untertitel (Englisch): | is adjustment for body size justified? |
Verlag: | Oxford Univ. Press |
Verlagsort: | Oxford |
Publikationstyp: | Sonstiges |
Sprache: | Englisch |
Datum der Erstveröffentlichung: | 26.01.2017 |
Erscheinungsjahr: | 2017 |
Datum der Freischaltung: | 27.06.2022 |
Band: | 11 |
Ausgabe: | 1 |
Seitenanzahl: | 2 |
Erste Seite: | S325 |
Letzte Seite: | S326 |
Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Mathematik |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 53 Physik / 530 Physik |
Peer Review: | Referiert |