BACKGROUND & AIMS In asymptomatic inflammatory bowel disease (IBD) patients, “monitoring” involves repeated testing aimed at early recognition of disease exacerbation. We aimed to determine the usefulness of repeated fecal calprotectin (FC) measurements to predict IBD relapses by a systematic literature review. METHODS An electronic search was performed in Medline, Embase and Cochrane from inception to April 2016. Inclusion criteria were prospective studies that followed patients with IBD in remission at baseline, and had at least 2 consecutive FC measurements with a test interval of 2 weeks to 6 months. Methodological assessment was based on the second Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. RESULTS A total of 1719 papers were identified; 193 were retrieved for full text review. Six studies met eligibility for inclusion. The time interval between FC tests varied between 1 to 3 months. Asymptomatic patients with IBD who had repeated FC measurements above the study’s cut-off level had a 53–83% probability of developing disease relapse within the next 2–3 months. Patients with repeated normal FC values had a 67–94% probability to remain in remission in the next 2–3 months. The ideal FC cut-off for monitoring could not be identified due to the limited number studies meeting inclusion criteria and heterogeneity between selected studies. CONCLUSIONS Two consecutively elevated FC values are highly associated with disease relapse, indicating a consideration to proactively optimize IBD therapy plans. More prospective data are necessary to assess whether FC monitoring improves health outcomes

Objectives The pharmacokinetics of infliximab are highly variable in children with Crohn's disease (CD), and a one-size-fits-all approach to dosing is inadequate. Model-based drug dosing can help individualize dosing strategies. We evaluated the predictive performance and clinical utility of a published population pharmacokinetic model of infliximab in children with CD. Methods Within a cohort of 34 children with CD who had infliximab trough concentrations measured, the pharmacokinetics of each patient was estimated in NONMEM® using a published population pharmacokinetic model. Infliximab concentrations were then predicted based on each patient's dosing history and compared to actual measured concentrations (n=59). In addition, doses 5-10 mg/kg and dosing intervals every 4-8 weeks were simulated in each patient to examine dose-trough relationships. Results Predicted concentrations were within ±1.0 μg/ml of actual measured concentrations for 88% of measurements. The median prediction error (i.e. measure of bias) was -0.15 μg/ml (95%CI: -0.37 to -0.05 μg/ml) and absolute prediction error (i.e. measure of precision) was 0.26 μg/ml (95%CI: 0.15 to 0.40 μg/ml). At standard maintenance dosing of 5 mg/kg every 8 weeks, a trough >3 μg/ml was predicted to be achieved in 32% of patients. To achieve a trough >3 μg/ml, a dosing interval ≤ every 6 weeks was predicted to be required in 29% of patients. Conclusions A published infliximab population pharmacokinetic model demonstrated accurate predictive performance in a pediatric CD population. Individualized infliximab dosing strategies in children with CD will be critical to consistently achieve trough concentrations associated with optimal outcomes.

A health care system is needed where care is based on the best available evidence and is delivered reliably, efficiently, and less expensively (best care at lower cost). In gastroenterology, anti-tumor necrosis factor (anti-TNF) agents represent the most effective medical therapeutic option for patients with moderate-to-severe inflammatory bowel disease (IBD), but are very expensive and account for nearly a quarter of the cost of IBD care, representing a major area of present and future impact in direct health care costs. The ImproveCareNow Network, consisting of over 55 pediatric IBD centers, seeks ways to improve the value of care in IBD – curtailing unnecessary costs and promoting better health outcomes through systematic and incremental quality improvement initiatives. This report summarizes the key evidence to facilitate the cost-effective use of anti-TNF agents for patients with IBD. Our review outlines the scientific rationale for initiating cost-reducing measures in anti-TNF use and focuses on three implementable strategies and four exploratory considerations through practical clinical guidelines, as supported by existing evidence. Implementable strategies can be readily integrated into today’s daily practice, while exploratory considerations can guide research to support future implementation.

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In order to better predict the pharmacokinetics (PK) of antibodies in children, and to facilitate dose optimization of antibodies in paediatric patients, there is a need to develop systems PK models that integrate ontogeny-related changes in human physiological parameters. Methods: A population-based physiological-based PK (PBPK) model to characterize antibody PK in paediatrics has been developed, by incorporating age-related changes in body weight, organ weight, organ blood flow rate and interstitial volumes in a previously published platform model. The model was further used to perform Monte Carlo simulations to investigate clearance vs. age and dose-exposure relationships for infliximab. Results: By estimating only one parameter and associated interindividual variability, the model was able to characterize clinical PK of infliximab from two paediatric cohorts (n = 141, 4-19 years) reasonably well. Model simulations demonstrated that only 50% of children reached desired trough concentrations when receiving FDA-labelled dosing regimen for infliximab, suggesting that higher doses and/or more frequent dosing are needed to achieve target trough concentrations of this antibody. Conclusion:The paediatric PBPK model presented here can serve as a framework to characterize the PK of antibodies in paediatric patients. The model can also be applied to other protein therapeutics to advance precision medicine paradigm and optimize antibody dosing regimens in children.