Validation of a population pharmacokinetic model of adalimumab in a cohort of patients with inflammatory bowel disease

Background: therapeutic monitoring of anti-TNF drugs and anti-drug antibody levels are useful for clinical decision-making, via the rationalization and optimization of the use of anti-TNF treatments. The objective of the present study was to validate the model of Ternant et al., in a cohort of patients with inflammatory bowel diseases (IBD). This model was originally established for patients with rheumatoid arthritis and was used in this study to optimize the adalimumab (ADA) dose and predict ADA trough levels (ATL). Methods: this study used concentration data points from 30 IBD patients who received ADA treatment between 2014 and 2015. A goodness-of-fit of the model was determined by evaluating the relationship between the observed ATL values and population model-predicted values (PRED) or individual model-predicted values (IPRED). Results: a total of 51 ADA concentration points were analyzed. The bias of the model was 2.39 (95% CI, 1.63-3.15) for PRED and 0.63 (95% CI, 0.23-1.03) for IPRED. The precision was 3.57 (95% CI, 2.90-4.13) and 1.53 (95% CI, 1.22-1.80), respectively. Conclusions: therapeutic drug monitoring involving ATL may allow the optimization of the treatment of IBD patients. The validation results of the phamacokinectic (PK) model for ADA in IBD patients are inadequate. However, additional studies will strengthen the bias and precision of the model

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Validation of a population pharmacokinetic model of adalimumab in a cohort of patients with inflammatory bowel disease.

BACKGROUND: therapeutic monitoring of anti-TNF drugs and anti-drug antibody levels are useful for clinical decision-making, via the rationalization and optimization of the use of anti-TNF treatments. The objective of the present study was to validate the model of Ternant et al., in a cohort of patients with inflammatory bowel diseases (IBD). This model was originally established for patients with rheumatoid arthritis and was used in this study to optimize the adalimumab (ADA) dose and predict ADA trough levels (ATL). METHODS: this study used concentration data points from 30 IBD patients who received ADA treatment between 2014 and 2015. A goodness-of-fit of the model was determined by evaluating the relationship between the observed ATL values and population model-predicted values (PRED) or individual model-predicted values (IPRED). RESULTS: a total of 51 ADA concentration points were analyzed. The bias of the model was 2.39 (95% CI, 1.63-3.15) for PRED and 0.63 (95% CI, 0.23-1.03) for IPRED. The precision was 3.57 (95% CI, 2.90-4.13) and 1.53 (95% CI, 1.22-1.80), respectively. CONCLUSIONS: therapeutic drug monitoring involving ATL may allow the optimization of the treatment of IBD patients. The validation results of the phamacokinectic (PK) model for ADA in IBD patients are inadequate. However, additional studies will strengthen the bias and precision of the model.

Cardioprotective effect of sevoflurane and propofol during anaesthesia and the postoperative period in coronary bypass graft surgery: a double-blind randomised study.

CONTEXT: Volatile anaesthetics may have direct cardioprotective properties due to effects similar to ischaemic preconditioning and postconditioning. Clinical results in cardiac surgery patients are controversial and may be related to the timing of administration of anaesthetics intraoperatively. OBJECTIVE: We hypothesised that the cardioprotective effect of sevoflurane in coronary bypass graft surgical patients would be greater if administration during anaesthesia continued in the ICU for at least 4 h postoperatively until weaning from mechanical ventilation. DESIGN: Double-blind, double-dummy, prospective, randomised and controlled clinical trial. SETTING: In a single centre between June 2006 and June 2007. PATIENTS: Seventy-five adult patients were assigned randomly to receive anaesthesia and postoperative sedation either with propofol (control, n = 37) or sevoflurane (n = 36). INTERVENTIONS: Myocardial biomarkers were measured before surgery, at the time of admission to the intensive care unit and at 6, 24, 48 and 72 h. The need for inotropic support, and lengths of stay in the intensive care unit and hospital were also recorded. MAIN OUTCOME MEASURES: Elevation of myocardial biomarkers was the primary endpoint. The secondary endpoints were haemodynamic events and lengths of stay in the intensive care unit and hospital. RESULTS: Necrosis biomarkers increased significantly in the postoperative period in both groups with no significant differences at any time. Inotropic support was needed in 72.7 and 54.3% of patients in the propofol and sevoflurane groups, respectively (P = 0.086). There were no significant differences in haemodynamic variables, incidence of arrhythmias, myocardial ischaemia or and lengths of stay in the ICU and hospital between the two groups. CONCLUSION: In patients undergoing coronary bypass graft surgery, continuous administration of sevoflurane as a sedative in the ICU for at least 4 h postoperatively did not yield significant improvements in the extent and time course of myocardial damage biomarkers compared to propofol.