Pharmacokinetics and Pharmacodynamics of Systemic Corticosteroids in Autoimmune and Inflammatory Diseases: A Review of Current Evidence.

Background And Objective: Systemic corticosteroids have a long history of use in the treatment of autoimmune and inflammatory diseases. Both efficacy and safety show large interindividual variability (IIV), suggesting that corticosteroids may have the potential for individualised dosing strategies to optimise therapy. This systematic review aims to provide an overview of current evidence on the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of systemic corticosteroids in patients with autoimmune and inflammatory diseases.

Adherence to low-dose methotrexate in children with juvenile idiopathic arthritis using a sensitive methotrexate assay.

Background: Low-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis. Unfortunately, a substantial part of patients has insufficient efficacy of MTX. A potential cause of this inadequate response is suboptimal drug adherence.

Negative impact of a health insurer-mandated de-simplification from a single-tablet regimen to a two-tablet regimen.

Objectives: Antiretroviral therapy (ART) accounts for a considerable proportion of HIV care expenses. In June 2021, a Dutch healthcare insurer implemented a mandatory policy to de-simplify branded RPV/TDF/FTC (Eviplera) into a two-tablet regimen containing rilpivirine (Edurant) and generic TDF/FTC as part of cost-saving measures. The objectives of this study were to evaluate the acceptance of this policy, the trends in ART dispensation, and cost developments.

Tacrolimus Variability and Clinical Outcomes in the Early Post-lung Transplantation Period: Oral Versus Continuous Intravenous Administration.

Background And Objective: High variability in tacrolimus pharmacokinetics directly after lung transplantation (LuTx) may increase the risk for acute kidney injury (AKI) and transplant rejection. The primary objective was to compare pharmacokinetic variability in patients receiving tacrolimus orally versus intravenously early after LuTx.

Methods: Pharmacokinetic and clinical data from 522 LuTx patients transplanted between 2010 and 2020 in two university hospitals were collected to compare orally administered tacrolimus to intravenous tacrolimus early post-transplantation.

Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen.

There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir.

Ocular surface disease in moderate-to-severe atopic dermatitis patients and the effect of biological therapy.

Atopic dermatitis (AD) is a chronic inflammatory skin disease for which new targeted therapies are currently available. Due to the increased rates of ocular surface disease (OSD) reported during treatment with these new targeted treatments, more insight into the occurrence and pathomechanism of OSD in moderate-to-severe AD patients is needed. Therefore, this review's first part highlights that most patients with moderate-to-severe AD already have characteristics of OSD before starting targeted treatment.

Elexacaftor/tezacaftor/ivacaftor in liver or kidney transplanted people with cystic fibrosis using tacrolimus, a drug-drug interaction study.

Background: The use of elexacaftor/tezacaftor/ivacaftor (ETI) in people with cystic fibrosis (pwCF) after solid organ transplantation is controversial because of potential drug-drug interactions (DDI) with tacrolimus. We aimed to improve insight into the safety and clinical benefits of co-administration of ETI and tacrolimus in liver or kidney transplanted adult pwCF.

Methods: In 5 pwCF, tacrolimus concentrations were monitored during 2 weeks before and 4 weeks after starting ETI treatment.

Vancomycin flushing reaction after intraperitoneal vancomycin: A case report.

Vancomycin has been reported to cause vancomycin flushing reaction (VFR), a hypersensitivity reaction that mostly occurs after intravenous administration. The incidence of VFR in a patient receiving intraperitoneal vancomycin is rare. We report a case of a female peritoneal dialysis (PD) patient with a PD-related peritonitis who developed VFR after intraperitoneal administration of 2000 mg vancomycin.

Functional determination of emicizumab in presence of factor VIII activity.

Background: Accurate measurement of emicizumab in the presence of factor (F) VIII is required in patients with severe hemophilia A treated with emicizumab, as well as additional need for FVIII substitution or emicizumab prophylaxis in patients with acquired or moderate to mild hemophilia A. However, the presence of FVIII potentially biases the results.

Objectives: To assess the impact of plasma FVIII activity on determined emicizumab levels and evaluate different strategies for correction for or preanalytical inhibition of FVIII.

Virological and immunological correlates of HIV posttreatment control after temporal antiretroviral therapy during acute HIV infection.

Objective: People with HIV rarely control viral replication after cessation of antiretroviral therapy (ART). We present a person with HIV with extraordinary posttreatment control (PTC) for over 23 years after temporary ART during acute HIV infection (AHI) leading to a new insight in factors contributing to PTC.

Design/methods: Viral reservoir was determined by HIV qPCR, Intact Proviral DNA Assay, and quantitative viral outgrowth assay.

Continuous infusion of cefiderocol in a critically ill patient with continuous venovenous haemofiltration.

Cefiderocol is a broad-spectrum cephalosporin antibiotic and is indicated in patients with difficult-to-treat Gram-negative bacterial infections. Cefiderocol is applied as a 2-4-times daily prolonged 3-h infusion. The therapeutic target of cefiderocol suggests that continuous infusion (CI) may be advantageous, since it is more likely to achieve 100% of time of the unbound concentration above the minimal inhibitory concentration (MIC).

Optimization of a Quantitative Anti-Drug Antibodies against Infliximab Assay with the Liquid Chromatography-Tandem Mass Spectrometry: A Method Validation Study and Future Perspectives.

Monoclonal antibodies (mAbs), such as infliximab, are important treatment options for different diseases. Immunogenicity is a major risk, resulting in anti-drug antibodies (ADAs), being associated with adverse events and loss of response, influencing long-term outcomes. The development of ADAs against infliximab is primarily measured by immunoassays like radioimmunoassay (RIA).

Busulfan Interlaboratory Proficiency Testing Program Revealed Worldwide Errors in Drug Quantitation and Dose Recommendations.

Background: The clinical outcomes of busulfan-based conditioning regimens for hematopoietic cell transplantation (HCT) have been improved by personalizing the doses to target narrow busulfan plasma exposure. An interlaboratory proficiency test program for the quantitation, pharmacokinetic modeling, and busulfan dosing in plasma was developed. Previous proficiency rounds (ie, the first 2) found that 67%-85% and 71%-88% of the dose recommendations were inaccurate, respectively.

Therapeutic Drug Monitoring of Ganciclovir in Cytomegalovirus-Infected Patients With Solid Organ Transplants and Its Correlation to Efficacy and Toxicity.

Background: Cytomegalovirus causes morbidity and mortality, especially in immunocompromised patients, and is treated with (val)ganciclovir. Therapeutic drug monitoring of ganciclovir is often performed; however, clinically established target trough levels corresponding to efficacy are lacking. In 2021, our clinic increased the target trough level for ganciclovir from 1 to 2 mg/L to 2-4 mg/L.

High dupilumab levels in tear fluid of atopic dermatitis patients with moderate-to-severe ocular surface disease.

Background: The patho-mechanism of ocular surface disease (OSD) in dupilumab-treated atopic dermatitis (AD) patients remains unclear. The aim of this study is to measure dupilumab levels in tear fluid and serum, and relate these findings to the severity of OSD during dupilumab treatment in AD patients.

Methods: This prospective study included dupilumab-treated moderate-to-severe AD patients who were seen by a dermatologist and an ophthalmologist before the start of dupilumab (baseline), and after 4 and 28 weeks of dupilumab treatment.

Therapeutic drug monitoring of thiopurines: Effect of reduced 6-thioguanine nucleotide target levels in inflammatory bowel disease patients.

Aims: The effect of the Dutch nationwide adjustment of reducing 6-thioguanine nucleotide (6-TGN) target values (from 600-1200 to 320-630 pmol/8 × 10 red blood cells [RBC]) on toxicity and clinical outcome of thiopurine treatment in patients with inflammatory bowel disease has not yet been established. Therefore, the authors determined the incidence of toxicity-induced discontinuations and efficacy at both target concentrations.

Methods: This retrospective study was performed in inflammatory bowel disease patients treated with azathioprine or mercaptopurine.

Anti-Xa Levels in Morbidly Obese Patients Using Apixaban or Rivaroxaban, Before and After Bariatric Surgery.

Background: Despite limited evidence about the efficacy and safety of anticoagulation in patients post bariatric surgery, both vitamin K antagonists (VKA) and direct-acting oral anticoagulants (DOACs) are commonly prescribed.

Aim: To evaluate plasma anti-Xa levels of DOACs in morbidly obese (MO) patients before and after a Roux-en-Y gastric bypass (RYGB) procedure.

Patients And Methods: Retrospective, cross-sectional, and longitudinal study of anti-Xa activity of apixaban or rivaroxaban in MO patients (N = 41).

A generic sample preparation method for the multiplex analysis of seven therapeutic monoclonal antibodies in human plasma or serum with liquid chromatography-tandem mass spectrometry.

Due to the increasing number of therapeutic monoclonal antibodies (mAbs) used in the clinic, there is an increasing need for robust analytical methods to quantify total mAb concentrations in human plasma for clinical studies and therapeutic drug monitoring. We developed an easy, rapid, and robust sample preparation method for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The method was validated for infliximab (IFX), rituximab (RTX), cetuximab (CTX), dupilumab (DPL), dinutuximab (DNX), vedolizumab (VDZ), and emicizumab (EMZ).

Prospective validation of a model-informed precision dosing tool for vancomycin in intensive care patients.

Aims: Vancomycin is an important antibiotic for critically ill patients with Gram-positive bacterial infections. Critically ill patients typically have severely altered pathophysiology, which leads to inefficacy or toxicity. Model-informed precision dosing may aid in optimizing the dose, but prospectively validated tools are not available for this drug in these patients.

Sustained effectiveness, safety and therapeutic drug monitoring of tioguanine in a cohort of 274 IBD patients intolerant for conventional therapies.

Background: Tioguanine (or thioguanine) is an alternative drug for IBD patients who fail prior conventional immunomodulating therapy.

Aim: To report effectiveness, safety and therapeutic drug monitoring in a cohort of patients with prolonged tioguanine maintenance therapy.

Methods: In this nationwide, multicentre study, medical records of tioguanine- using IBD patients were retrospectively reviewed.