@inproceedings{DemarisGrišićHuisingaetal.2020,
  author    = {D{\´e}maris, Alise and Grišić, Ana-Marija and Huisinga, Wilhelm and Walter, Reinisch and Kloft, Charlotte},
  title     = {Evaluation of dosing strategies of anti-TNF alpha monoclonal antibodies using pharmacokinetic modelling and simulation},
  series = {Journal of Crohn's and Colitis},
  volume    = {14},
  booktitle = {Journal of Crohn's and Colitis},
  number    = {Supp. 1},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {1873-9946},
  doi       = {10.1093/ecco-jcc/jjz203.201},
  pages     = {S171 -- S172},
  year      = {2020},
  abstract  = {Background: Anti-TNFα monoclonal antibodies (mAbs) are a well-established treatment for patients with Crohn's disease (CD). However, subtherapeutic concentrations of mAbs have been related to a loss of response during the first year of therapy1. Therefore, an appropriate dosing strategy is crucial to prevent the underexposure of mAbs for those patients. The aim of our study was to assess the impact of different dosing strategies (fixed dose or body size descriptor adapted) on drug exposure and the target concentration attainment for two different anti-TNFα mAbs: infliximab (IFX, body weight (BW)-based dosing) and certolizumab pegol (CZP, fixed dosing). For this purpose, a comprehensive pharmacokinetic (PK) simulation study was performed. Methods: A virtual population of 1000 clinically representative CD patients was generated based on the distribution of CD patient characteristics from an in-house clinical database (n = 116). Seven dosing regimens were investigated: fixed dose and per BW, lean BW (LBW), body surface area, height, body mass index and fat-free mass. The individual body size-adjusted doses were calculated from patient generated body size descriptor values. Then, using published PK models for IFX and CZP in CD patients2,3, for each patient, 1000 concentration-time profiles were simulated to consider the typical profile of a specific patient as well as the range of possible individual profiles due to unexplained PK variability across patients. For each dosing strategy, the variability in maximum and minimum mAb concentrations (Cmax and Cmin, respectively), area under the concentration-time curve (AUC) and the per cent of patients reaching target concentration were assessed during maintenance therapy. Results: For IFX and CZP, Cmin showed the highest variability between patients (CV ≈110\% and CV ≈80\%, respectively) with a similar extent across all dosing strategies. For IFX, the per cent of patients reaching the target (Cmin = 5 µg/ml) was similar across all dosing strategies (~15\%). For CZP, the per cent of patients reaching the target average concentration of 17 µg/ml ranged substantially (52-71\%), being the highest for LBW-adjusted dosing. Conclusion: By using a PK simulation approach, different dosing regimen of IFX and CZP revealed the highest variability for Cmin, the most commonly used PK parameter guiding treatment decisions, independent upon dosing regimen. Our results demonstrate similar target attainment with fixed dosing of IFX compared with currently recommended BW-based dosing. For CZP, the current fixed dosing strategy leads to comparable percentage of patients reaching target as the best performing body size-adjusted dosing (66\% vs. 71\%, respectively).},
  language  = {en}
}
@article{SchomoellerSchugardtKotschetal.2021,
  author    = {Schom{\"o}ller, Anne and Schugardt, Monique and Kotsch, Peggy and Mayer, Frank},
  title     = {The effect of body composition on cycling power during an incremental test in young athletes},
  series = {Journal of strength and conditioning research : the research journal of the NSCA / National Strength \& Conditioning Association},
  volume    = {35},
  journal   = {Journal of strength and conditioning research : the research journal of the NSCA / National Strength \& Conditioning Association},
  number    = {11},
  publisher = {Lippincott Williams \& Wilkins},
  address   = {Philadelphia},
  issn      = {1064-8011},
  doi       = {10.1519/JSC.0000000000003271},
  pages     = {3225 -- 3231},
  year      = {2021},
  abstract  = {Schomoller, A, Schugardt, M, Kotsch, P, and Mayer, F. The effect of body composition on cycling power during an incremental test in young athletes. J Strength Cond Res 35(11): 3225-3231, 2021-As body composition (BC) is a modifiable factor influencing sports performance, it is of interest for athletes and coaches to optimize BC to fulfill the specific physical demands of one sport discipline. The purpose of this study is to test the impact of body fat (BF) and fat-free mass (FFM) on aerobic performance in young athletes. Body composition parameters were evaluated among gender and age groups of young athletes undergoing their mandatory health examination. The maximal power (in Watts per kilogram body mass) of a stepwise incremental ergometer test was compared between 6 BC types: high BF, high FFM, high BF and high FFM, normal BC values, low BF, and low FFM. With increasing age (11-13 vs. 14-16 years) BF decreased and FFM increased in both genders. Both BC parameters, as well as body mass, correlated moderately with performance output (r = 0.36-0.6). Subjects with high BF or high FFM or both had significantly lower ergometer test results compared with those with low BF and FFM in all age and gender groups (p < 0.05). The finding that high levels of BF and FFM are detrimental for cycle power output is important to consider in disciplines that demand high levels of aerobic and anaerobic performance.},
  language  = {en}
}