Prediction of treatment failure during infliximab induction therapy in inflammatory bowel disease patients based on pharmacokinetic and pharmacodynamic modeling

Kimura, Koji; Yoshida, Atsushi; Katagiri, Fumihiko; Takayanagi, Risa; Yamada, Yasuhiko

doi:10.1016/j.ejps.2020.105317

Cited by 6 publications

(7 citation statements)

References 54 publications

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“…In addition, UC is often under-represented in the IBD populations used for modelling activities. Out of the 22 selected articles reporting on an IBD population, only eight included more than 30% of UC patients [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. This does not reflect real life populations, as the prevalence of UC in the IBD population is quite similar or even higher than CD [ 2 ].…”

Section: Resultsmentioning

confidence: 99%

Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmacokinetic Models: Results from a Comprehensive Review

et al. 2022

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Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis α monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome. Thus, this review aims to compile and analyse published population PK models of IFX in UC and ASUC patients, and to assess the current knowledge on disease activity impact on IFX PK. For this, a semi-systematic literature search was conducted, from which 26 publications including a population PK model analysis of UC patients receiving IFX therapy were selected. Amongst those, only four developed a model specifically for UC patients, and only three populations included severe UC patients. Investigations of disease activity impact on PK were reported in only 4 of the 14 models selected. In addition, the lack of reported model codes and assessment of predictive performance make the use of published models in a clinical setting challenging. Thus, more comprehensive investigation of PK in UC and ASUC is needed as well as more adequate reports on developed models and their evaluation in order to apply them in a clinical setting.

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Section: Resultsmentioning

confidence: 99%

Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmacokinetic Models: Results from a Comprehensive Review

et al. 2022

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“…In conclusion, his study showed that the presented PK/PD model is capable of predicting sequential changes of therapeutic effect of UST for IBD, and the implications for e cacy of the different dosage regimens could be evaluated by simulation with various dosage regimens. These ndings are useful for model-informed precision dosing of individual IBD patients by predicting the serum UST concentration and therapeutic effect in individual patients [30].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic-pharmacodynamic modelling and simulation of ustekinumab for inflammatory bowel disease

Kimura

Yoshida

2022

Preprint

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Ustekinumab (UST) therapy is effective for induction and maintenance therapy for inflammatory bowel disease (IBD). Although there are differences in dosage regimen among countries and indications, and the differences have implications for efficacy, the implications have yet to be analysed by a model-informed approach. The aim of this study is to evaluate the implications for efficacy of the different dosage regimens of UST for IBD using our pharmacokinetic-pharmacodynamic (PK/PD) model. We constructed a PK/PD model based on an indirect response model with an effect compartment and simulated the sequential changes of therapeutic effect following various dosage regimens. Sequential changes in the therapeutic effect obtained with our model were in good agreement with the observed values following repeated administration of UST for IBD patients. The simulation indicated the importance of an initial intravenous administration of UST for IBD patients. Furthermore, the dose interval of maintenance therapy at every 8 weeks was marginally more effective than at every 12 weeks, though there was almost no difference in the fluctuation range, and a stable therapeutic effect was obtained by both dosage regimens. The results showed that the presented PK/PD model is capable of predicting sequential changes in the therapeutic effect of UST for IBD, and the implications for efficacy of the different dosage regimens could be evaluated by simulation with various dosage regimens.

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“…Furthermore, in each patient, using actual CDAI and partial Mayo score, individual PK parameters, population PD parameters, and the PK/PD model in Fig. 1, individual PD parameters were calculated using NONMEM and PDx-POP (versions 7.3.0 and 5.2.2, respectively; ICON Clinical Research LLC, North Wales, Pennsylvania, USA), using the MCMC Bayesian analysis method with an MU model that was previously reported [22]. The individual K anti-TNFα 0 / K else ratio was shown in Supplementary Table 1, Supplemental Digital Content 1, http://links.lww.com/EJGH/A755.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In previous studies, we constructed a PK and pharmacodynamic (PK/PD) model of anti-TNFα for IBD, which considered PD factors, including the cytokine profile [21][22][23]. We also reported that the PK/PD parameters of IFX in each patient were able to be calculated using the PK/ PD model and the Markov chain Monte Carlo (MCMC) Bayesian analysis method in the induction phase [22]. The aim of this study is to reveal useful predictors of the response to anti-TNFα treatment from baseline to 2 months after initial administration of anti-TNFα for Background It is necessary to find reliable and appropriate predictors of primary response to anti-TNFα therapy (infliximab and adalimumab) in inflammatory bowel disease (IBD) so as to avoid treatment failure and select optimal treatment.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Predictor of primary response to antitumor necrosis factor-α therapy for inflammatory bowel disease: a single-center observational study

Yoshida¹,

Kimura

Morizane³

et al. 2022

European Journal of Gastroenterology &Amp; Hepatology

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K else and the improvement of disease activity index was shown in Crohn's disease patients (univariate: estimated value 2.4; P = 0.003; and multivariate: 1.8; P = 0.012) and ulcerative colitis patients (univariate: 0.12; P = 0.011), and no other factors were significant. Conclusion This is the first study to present a useful predictor of primary response to anti-TNFα of individual IBD patients at second administration. The K anti-TNFα 0 /K else ratio may help to select the optimal therapeutic drug and avoid the improper continuous administration of anti-TNFα in the induction phase.

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Prediction of treatment failure during infliximab induction therapy in inflammatory bowel disease patients based on pharmacokinetic and pharmacodynamic modeling

Cited by 6 publications

References 54 publications

Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmacokinetic Models: Results from a Comprehensive Review

Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmacokinetic Models: Results from a Comprehensive Review

Pharmacokinetic-pharmacodynamic modelling and simulation of ustekinumab for inflammatory bowel disease

Predictor of primary response to antitumor necrosis factor-α therapy for inflammatory bowel disease: a single-center observational study

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