Quantification of Adeno-Associated Viral Genomes in Purified Vector Samples by Digital Droplet Polymerase Chain Reaction.

Adeno-associated virus (AAV) is a non-pathogenic virus used as a delivery vehicle to transfer therapeutic genes into patients. Accurate quantification of AAV genome copy number in vector preparations is essential for bioprocess optimization and dosage calculation in both preclinical and clinical studies of AAV-based gene therapy products. Currently, a consensus protocol for AAV viral genome titration is lacking.

Evaluation of serum cytokines and acute phase proteins as possible pharmacodynamic biomarkers to monitor endoscopic remission during ustekinumab therapy in patients with Crohn's disease.

Background: Since not all Crohn's disease (CD) patients respond adequately to ustekinumab therapy, biomarkers could aid to monitor treatment response and optimize therapeutic outcomes.

Objectives: To explore the dynamics of serum biomarker concentrations to monitor the response to ustekinumab treatment in CD patients.

Design: Retrospective, exploratory study to evaluate concentrations of serum cytokines and acute phase proteins and their relation to endoscopic remission in CD patients during ustekinumab treatment.

Tissue Exposure does not Explain Non-Response in Ulcerative Colitis Patients with Adequate Serum Vedolizumab Concentrations.

Background And Aims: Some patients with ulcerative colitis [UC] do not respond to vedolizumab treatment despite adequate drug exposure in serum. This study aimed to investigate vedolizumab in tissue and questioned whether insufficient tissue exposure could explain non-response in UC patients with adequate serum vedolizumab concentrations.

Methods: A paired serum sample and colonic mucosal biopsy was collected from 40 UC patients [20 endoscopic responders, 20 non-responders] at week 14 of vedolizumab treatment.

Development and validation of immunoassays for monitoring of guselkumab and anti-guselkumab antibodies in patients with moderate-to-severe psoriasis.

Therapeutic drug monitoring, which is the measurement of drug concentrations in the blood, is a useful tool to guide clinical decision-making and treatment adjustments, on the condition that drug concentrations are correlated with treatment response. For guselkumab, an anti-IL-23 monoclonal antibody for the treatment of moderate-to-severe psoriasis, such a concentration-response relationship could not yet be determined as no commercial assays for the quantification of this drug or antibodies against this drug are available. Therefore, the aim of this study was to develop and validate immunoassays for the quantification of guselkumab and anti-guselkumab antibodies according to the guidelines of the European Medicines Agency (EMA).

Evaluating an easy sampling method using dried blood spots to determine vedolizumab concentrations.

An association between vedolizumab (VDZ) trough concentrations and therapeutic outcome has been observed in patients with inflammatory bowel diseases. VDZ samples are typically collected via venous sampling for therapeutic drug monitoring (TDM), but can alternatively be collected via dried blood spot (DBS) samples, which can be used for intensive sampling to investigate pharmacokinetic profiles. Therefore, we have developed a DBS method for determining VDZ concentrations and validated this method by comparing VDZ measurements in paired DBS and venous patient samples.

Regulatory Role for NK Cells in a Mouse Model of Systemic Juvenile Idiopathic Arthritis.

Mice deficient in IFN-γ (IFN-γ knockout [KO] mice) develop a systemic inflammatory syndrome in response to CFA, in contrast to CFA-challenged wild-type (WT) mice who only develop a mild inflammation. Symptoms in CFA-challenged IFN-γ KO resemble systemic juvenile idiopathic arthritis (sJIA), a childhood immune disorder of unknown cause. Dysregulation of innate immune cells is considered to be important in the disease pathogenesis.

Achieving Mucosal Healing in Inflammatory Bowel Diseases: Which Drug Concentrations Need to Be Targeted?

Biologicals introduced a major shift in the treatment of patients suffering from inflammatory bowel diseases. Despite providing a tight disease control for many patients, a considerable proportion of patients will fail to respond favorably to treatment or will lose response over time. Therapeutic drug monitoring emerged as a valuable tool to guide clinical decision making as serum drug concentrations have been linked to outcomes.

Ustekinumab Exposure-outcome Analysis in Crohn's Disease Only in Part Explains Limited Endoscopic Remission Rates.

Background And Aims: Ustekinumab, an anti-IL12/23p40 monoclonal antibody, has been approved for Crohn's disease [CD]. Real-life data in CD patients receiving ustekinumab intravenously [IV] during induction, followed by subcutaneous [SC] maintenance, are lacking. We assessed efficacy of ustekinumab and studied exposure-response correlations.

Immunogenicity is not the driving force of treatment failure in vedolizumab-treated inflammatory bowel disease patients.

Background And Aim: The pivotal GEMINI trials reported low immunogenicity of vedolizumab. However, anti-vedolizumab antibodies (AVA) are frequently underestimated because most assays are not drug-tolerant and unable to detect antidrug antibodies while there is drug in the circulation. This study aimed to explore which antidrug antibody assay is best suited to detect AVA and investigated immunogenicity of vedolizumab in inflammatory bowel disease (IBD) patients discontinuing vedolizumab therapy.