This multinational, randomized, double-blind trial, (ClinicalTrials.gov identifier NCT02149121) was designed to demonstrate equivalence in pharmacokinetics and efficacy between CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA). Adults with active RA were treated with CT-P10, United States-sourced RTX (US-RTX; Rituxan®), or European Union-sourced RTX (EU-RTX; MabThera®) at weeks 0 and 2. The co-primary pharmacokinetic endpoints were area under the serum concentration–time curve (AUC) from time zero to last measurable concentration (AUC0–last), AUC from time zero to infinity (AUC0–∞), and maximum concentration (Cmax) after two infusions. The primary efficacy endpoint was change from baseline to week 24 in Disease Activity Score using 28 joints-C-reactive protein (DAS28-CRP). Pharmacodynamics, immunogenicity, and safety were also assessed. 372 patients were randomly assigned to CT-P10 (n = 161) or RTX (n = 211 [US-RTX, n = 151; EU-RTX, n = 60]). For the co-primary pharmacokinetic endpoints, 90% confidence intervals (CI) for ratios of geometric means (CT-P10/US-RTX, CT-P10/EU-RTX or EU-RTX/US-RTX) all fell within the equivalence margin of 80–125%. Adjusted least squares (LS) mean (standard error) change from baseline in DAS28-CRP at week 24 was −2.13 (0.175) for CT-P10 and −2.09 (0.176) for RTX. The 95% CI (−0.29, 0.21) of the estimated treatment difference between CT-P10 and RTX (−0.04) was entirely within the efficacy equivalence margin of ±0.5. Pharmacodynamics, immunogenicity, and safety profiles were similar for CT-P10 and RTX. The pharmacokinetics of CT-P10, US-RTX, and EU-RTX were equivalent. CT-P10 and RTX were also equivalent in terms of efficacy and displayed similar pharmacodynamic, immunogenicity, and safety profiles up to week 24.

Objective:Therapeutic drug monitoring (TDM) enables individualization in the treatment to optimize clinical benefit and minimize drugs' side effects. Critically ill septic patients represent a challenge for antimicrobial treatment because of pathophysiological impact of sepsis on pharmacokinetics of drugs. The aim of this study was to assess the appropriateness of gentamicin and amikacin dosing in critically and noncritically ill patients, as well as to estimate the need for its regular therapeutic monitoring.Subjects and Methods:It was a prospective study which included 31 patients on gentamicin and 16 patients on amikacin from four different units who met the inclusion criteria. Trough concentrations of drugs were measured in serum just before third or fourth dose of antibiotic, whereas peak concentrations were measured in serum 1 h after the completion of drug administration (steady state). Relevant data on patients' clinical course of disease, comorbidities, and concomitant medication were collected from medical charts in order to identify their possible influence on drugs' concentrations.Results:Peak concentrations of amikacin were in reference range in 81.8% critically ill and in 80% of noncritically ill patients (P = 0.931). Peak concentrations of gentamicin were in reference range in 88.9% critically ill and in 77.3% of noncritically ill patients (P = 0.457).Conclusion:Serum concentrations of aminoglycosides (amikacin and gentamicin) were in reference range in most of the patients in our study, suggesting that dosing of these drugs in the University Hospital Clinical Center, Banja Luka, was adequate. In patients without kidney or liver disease, regular TDM of aminoglycosides is not necessary.