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Poster presentations: Clinical: Therapy and Observation 2020

P542 The effect of age on infliximab pharmacokinetics in patients with inflammatory bowel disease

W. Kantasiripitak1, B. Verstockt2,3, T. Lobatón2,3,4, D. Thomas1, A. Gils1, S. Vermeire2,3, M. Ferrante2,3, E. Dreesen1

1Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium, 2Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium, 3Department of Chronic Diseases Metabolism and Ageing, KU Leuven, Leuven, Belgium, 4Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium

Background

Data remain scarce in terms of efficacy and safety of infliximab (IFX) treatment in elderly patients with inflammatory bowel disease.1 Our aim was to employ a population pharmacokinetic (popPK) model to improve our understanding of factors impacting variability in IFX exposure in elderly patients with ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

IFX concentration–time data during induction therapy (week 2, 6 and 14) of 104 patients were obtained from a retrospective case–control study2 (n = 79) and a single centre database search (n = 25) at our institution. Patients ≥65 years old were categorised as elderly. A popPK model was developed using NONMEM 7.4. Relationships between IFX exposure and the first endoscopic remission (ER) assessment after the start of IFX therapy (absence of ulceration [CD] and Mayo endoscopic sub-score ≤0 [UC]) were evaluated.

Results

Median age was 62 years (IQR 38–68). A total of 46 of 104 patients (44%) were elderly. A one-compartment model with linear clearance showed adequate descriptive and predictive ability. The estimated popPK parameters (typical value [%RSE]) were clearance CL (0.346 l/day [4%]) and volume of distribution V (6.42 l [5%]). The elimination half-life of IFX in the elderly was not significantly different from the non-elderly (12.6 days vs. 11.4 days, p = 0.356). IFX clearance was higher with the presence of antibodies to IFX (ATI; drug-tolerant assay; 32% higher), higher fat-free mass (FFM; 1.4% per kg), lower serum albumin (4.5% per g/l), and younger age (0.6% per year). These covariates explained 10% of interindividual variability (IIV) in IFX CL. However, 33% of the variability remained unexplained. Contrary to Paul et al.3, proportions of patients with ATI were not significantly different between elderly and non-elderly (13% [6/46] vs. 14% [8/58], p = 1.000). FFM and serum albumin were significantly lower in elderly patients (p = 0.007 and p = 0.0004, respectively). Due to the large remaining IIV, IFX exposures (trough concentrations and estimated area under the PK curve) were not significantly different between elderly and non-elderly (Figure 1). A total of 19/72 patients (26%, 32/104 had no endoscopy data) achieved ER. There was no significant difference between the proportion of elderly and non-elderly with ER (p = 1.000). IFX trough concentrations at w6 were significantly higher in patients achieving ER (p = 0.016).

Conclusion

Older age is an independent predictor of lower clearance. However, the effect of age did not pronounce on infliximab exposure in our elderly patient cohort as a result of confounding effects of fat-free mass and serum albumin.

References:

LeBlanc et al. 2019. World J Gastroenterol.

Lobatón et al. 2015. Aliment Pharmacol Ther.

Paul et al. 2019. Aliment Pharmacol Ther.