Explore the vast range of titles available.

There are limited data on the role of proactive therapeutic drug monitoring (TDM) of ustekinumab (UST) in patients with inflammatory bowel disease (IBD). This study investigated the efficacy and safety of proactive TDM in IBD patients treated with subcutaneous (sc) UST. This was a retrospective single-center cohort study. Consecutive patients with IBD who received maintenance subcutaneous (sc) UST therapy and underwent TDM from January 2017 to February 2023 were eligible for inclusion. Patients were followed through May 2024 or until drug discontinuation or an IBD-related surgery. Patients underwent either at least one proactive TDM or reactive TDM only. Survival analysis was performed to evaluate drug persistence, defined as no need for drug discontinuation due to loss of response, serious adverse event (SAE) or an IBD-related surgery, and IBD-related hospitalizations. The study population consisted of 83 patients (proactive TDM, n = 46) of whom 67 (81%) had Crohn's disease. Patients who had at least one proactive TDM had higher drug persistence (Log-rank P < .001) and less IBD-related hospitalization (Log-rank P = .012) compared to patients undergoing only reactive TDM. In multivariable COX proportional hazard regression analysis, at least one proactive TDM was associated with increased drug persistence (hazard ratio [HR]: 5; 95% confidence interval [95% CI], 2-10; P < .001) and decreased IBD-related hospitalization (HR: 0.24; 95% CI, 0.07-0.83; P = .024). There was no SAE reported. This retrospective study showed that proactive TDM is associated with increased drug persistence and decreased IBD-related hospitalization in IBD patients treated with sc UST.

Abstract Background There are limited data regarding therapeutic drug monitoring (TDM) of non-anti-tumor necrosis factor therapy in inflammatory bowel disease (IBD). This study aimed to evaluate the efficacy of proactive TDM in IBD patients treated with intravenous (iv) vedolizumab (VDZ). Methods This single-center retrospective cohort study included consecutive IBD patients treated with maintenance iv VDZ therapy undergoing TDM from November 2016 to March 2023. Patients were followed through June 2023 and were divided in to 2 groups: those who had at least 1 proactive TDM vs those who underwent only reactive TDM. A survival analysis was performed to evaluate drug persistence, defined as no need for drug discontinuation due to loss of response, serious adverse event, or an IBD-related surgery. Results The study population consisted of 94 patients (proactive TDM, n = 72) with IBD (ulcerative colitis, n = 53). Patients undergoing at least 1 proactive TDM compared with patients having only reactive TDM demonstrated a higher cumulative probability of drug persistence (Log-rank P < .001). In multivariable Cox proportional hazard regression analysis, at least 1 proactive TDM was the only factor associated with drug persistence (hazard ratio, 14.3; 95% confidence interval [CI], 3.8-50; P < .001). A ROC analysis identified a VDZ concentration of 12.5 µg/mL as the optimal drug concentration threshold associated with drug persistence (area under the ROC curve: 0.691; 95% CI, 0.517-0.865; P = .049). Conclusion In this single-center retrospective study reflecting real-life clinical practice, proactive TDM was associated with increased drug persistence in patients with IBD treated with iv VDZ. Lay Summary There are limited data regarding therapeutic drug monitoring (TDM) of non-anti-tumor necrosis factor therapy in inflammatory bowel disease (IBD). We found that proactive TDM was associated with drug persistence in patients with IBD treated with vedolizumab. Moreover, a vedolizumab concentration of 12.5 µg/mL was identified as the optimal drug concentration threshold associated with drug persistence.

Therapeutic drug monitoring (TDM) is a tool used to integrate pharmacokinetic and pharmacodynamics knowledge to optimize and personalize various drug therapies. The optimization of drug dosing may improve treatment outcomes, reduce toxicity, and reduce the risk of developing drug resistance. To adequately implement TDM, accurate and precise analytical procedures are required. In clinical practice, blood is the most commonly used matrix for TDM; however, less invasive samples, such as dried blood spots or non-invasive saliva samples, are increasingly being used. The choice of sample preparation method, type of column packing, mobile phase composition, and detection method is important to ensure accurate drug measurement and to avoid interference from matrix effects and drug metabolites. Most of the reported procedures used liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) techniques due to its high selectivity and sensitivity. High-performance chromatography with ultraviolet detection (HPLC-UV) methods are also used when a simpler and more cost-effective methodology is desired for clinical monitoring. The application of high-performance chromatography with fluorescence detection (HPLC-FLD) with and without derivatization processes and high-performance chromatography with electrochemical detection (HPLC-ED) techniques for the analysis of various drugs in biological samples for TDM have been described less often. Before chromatographic analysis, samples were pretreated by various procedures—most often by protein precipitation, liquid–liquid extraction, and solid-phase extraction, rarely by microextraction by packed sorbent, dispersive liquid–liquid microextraction. The aim of this article is to review the recent literature (2010–2020) regarding the use of liquid chromatography with various detection techniques for TDM.

In patients with inflammatory bowel disease, proactive therapeutic drug monitoring of infliximab over a 2-year period was associated with higher rates of mucosal healing and lower surgical requirements compared with a conventional cohort treated without therapeutic drug monitoring.AbstractBackgroundIncreasing evidence supports the use of reactive therapeutic drug monitoring (TDM) in Crohn’s disease (CD) and ulcerative colitis (UC) following secondary loss of response. It is still unknown if proactive TDM can improve clinical outcomes.MethodsConsecutive patients completing infliximab (IFX) induction therapy were prospectively allocated into a proactive TDM protocol (pTDM). Before the fourth infusion and every 2 infusions, IFX trough levels and antidrug antibodies were measured using a drug-sensitive assay (Theradiag, Lisa Tracker). Treatment was proactively escalated aiming at an IFX trough level between 3 and 7 ug/mL (CD) and 5 and 10 ug/mL (UC). A retrospective cohort treated with IFX but without TDM served as the reference group. End points included the need for surgery, hospitalization, treatment discontinuation, and mucosal healing at 2 years of follow-up.ResultsTwo hundred five patients were included, 56 in the proactive regimen. Treatment escalation was more common in pTDM patients (76.8% vs 25.5%; P < 0.001), who also required less surgery (8.9% vs 20.8%; P = 0.032) and presented higher rates of mucosal healing (73.2% vs 38.9%; P < 0.0001). Proactive TDM significantly decreased the odds of reaching any unfavorable outcome (odds ratio, 0.358; 95% confidence interval, 0.188–0.683; P = 0.002).ConclusionsProactive TDM is associated with fewer surgeries and higher rates of mucosal healing than conventional non-TDM-based management.

Therapeutic drug monitoring (TDM) is a fundamental tool when administering drugs that have a limited dosage or high toxicity, which could endanger the lives of patients. To carry out this monitoring, one can use different biological fluids, including blood, plasma, serum, and urine, among others. The help of specialized methodologies for TDM will allow for the pharmacodynamic and pharmacokinetic analysis of drugs and help adjust the dose before or during their administration. Techniques that are more versatile and label free for the rapid quantification of drugs employ biosensors, devices that consist of one element for biological recognition coupled to a signal transducer. Among biosensors are those of the optical biosensor type, which have been used for the quantification of different molecules of clinical interest, such as antibiotics, anticonvulsants, anti-cancer drugs, and heart failure. This review presents an overview of TDM at the global level considering various aspects and clinical applications. In addition, we review the contributions of optical biosensors to TDM.

Surface-enhanced Raman spectroscopy (SERS) has been widely used in the field of therapeutic drug monitoring (TDM) because of its powerful fingerprinting capability. In this paper, we used an in situ synthesis method to anchor Ag nanoparticles (AgNPs) on the surface of MIL-101(Cr) to obtain MIL-101(Cr)@Ag. Owing to the large specific surface area and ultra-high porosity of MIL-101(Cr)@Ag, we developed a method for the determination of chlorpromazine hydrochloride (CPZ) and aminophylline (AMP) in human serum by using it as a solid-phase extraction sorbent and SERS substrate. The label-free TDM-SERS method was able to evaluate the levels of CPZ and AMP in serum samples with detection limits as low as 8.91 × 10–2 µg/mL and 3.4 × 10–2 µg/mL, respectively. In addition, influencing factors including sample solution pH, AgNO3 concentration, drug adsorption time, and the amount of sample solution were optimized. This protocol provides a new method with good selectivity, stability, reproducibility, homogeneity, and sensitivity for the determination of small-molecule drug content in serum samples. This label-free TDM-SERS method will help to achieve rapid individualized dosing regimens in clinical practice and has potential applications in the field of TDM.

[This corrects the article DOI: 10.3389/fphar.2022.828094.].

Among the most anticipated and discussed segments of the pharmaceutical market, biosimilars are finally beginning to exert a greater impact on practice. ASHP's Biosimilars & Biologics: Implementation and Monitoring in a Healthcare Setting is an authoritative, evidence-based resource that provides an in-depth perspective on all areas related to these innovative drugs.

We evaluated the activity of piperacillin in relation to increasing tazobactam concentration against ESBL-producing Enterobacterales collected from patients with bacteraemia. Increasing tazobactam concentration (4, 12 or 24 mg/L) exerted a reduction of piperacillin MICs under the clinical breakpoint in a concentration-dependent manner (0%, 60% and 90% of clinical isolates). Also, activity of piperacillin/tazobactam based at higher achievable serum concentrations (123/14 mg/L) is needed to reduce the bacterial growth in 92% of ESBL-producers. Changes in the piperacillin MIC in relation to increasing tazobactam suggest that realtime TDM could be used for driven antimicrobial therapy with piperacillin/tazobactam in BSI due to ESBL strains.

Background: Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, necessitates long-term medical therapy to manage symptoms and prevent complications. Therapeutic drug monitoring (TDM) has emerged as a strategy to optimize treatment efficacy, particularly with anti-tumour necrosis factor (anti-TNF) alpha drugs. This review explores the role of TDM for non-anti-TNF advanced therapies in IBD, focusing on vedolizumab, ustekinumab, tofacitinib, upadacitinib, risankizumab and ozanimod. Methods: The literature search, conducted through OVID (Medline) and PubMed, delves into proactive versus reactive TDM, timing of monitoring and methods for measuring drug levels and anti-drug antibodies. Results: While ustekinumab and vedolizumab exhibit exposure–response relationships, consensus on target levels and the role of TDM adjustments remains elusive. Limited data on risankizumab suggest a dose-dependent response, while for small molecule therapies (janus kinase inhibitors and ozanimod), the absence of real-world data and commercially available TDM tools pose challenges. Conclusion: At present, with the available data, there is a limited role for TDM in non-anti-TNF biologic and small-molecule therapies. This review underscores the need for further research to delineate the utility of TDM in guiding treatment decisions for these agents.