Tumour necrosis factor inhibitors in Ulcerative colitis: real-world data on Therapeutic drug monitoring and evaluation of current treatment targets (STRIDE II).

Background: The benefit of therapeutic drug monitoring (TDM) and implementation of recommendations from the Selection of Therapeutic Targets in Inflammatory Bowel Disease (IBD, STRIDE) are discussed in the IBD community. We report real-world data in ulcerative colitis patients receiving first-line tumour necrosis factor inhibitor (TNFi) treatment followed by TDM, and assess how implementation of the STRIDE II recommendations might affect clinical practice.

Methods: Adult, biologically naïve UC patients starting TNFi between 2014 and 2021 at Oslo University Hospital were included in a medical chart review study, and data were collected at three and twelve months after the start of treatment.

A simple automated assay format for measuring multiple immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have improved survival rates in oncology, but there is a rising concern for immune-related adverse health outcomes. Monitoring drug serum concentration would enable tailored dosing, however this strategy has not yet been evaluated for ICIs. Fully automated analyte capture assays with time-resolved fluorometry using protein A as tracer, were developed for three different ICIs; the cytotoxic T lymphocyte Antigen-4 (CTLA4) inhibitor ipilimumab (Yervoy; Bristol-Myers Squibb) and the Programmed Death-1 (PD-1) inhibitors nivolumab (Opdivo; Bristol-Myers Squibb) and pembrolizumab (Keytruda; Merck).

Efficacy of a TNF inhibitor in chronic low back pain with Modic changes type 1: The BackToBasic study A randomized controlled trial.

Objective: The efficacy of TNF inhibitors for treating chronic low back pain with Modic changes is uncertain. This study investigated the superiority of infliximab over placebo in patients with Modic changes type 1.

Methods: In this multicenter, randomized, triple-blind, placebo-controlled trial, patients aged 18-65 with moderate to severe chronic low back pain and Modic changes type 1 were enrolled from five Norwegian public hospitals between January 2019 and October 2022.

Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial.

Objectives: The objectives of this study are to identify a therapeutic serum level for adalimumab associated with remission and low disease activity in patients with rheumatoid arthritis.

Methods: Associations between serum adalimumab trough levels and disease activity were examined using longitudinal data from a 48-week randomised phase III trial including patients with tumour necrosis factor inhibitor-naïve rheumatoid arthritis with active disease starting adalimumab treatment. Disease activity was classified according to 28-joint Disease Activity Score (DAS28)-erythrocyte sedimentation rate and C reactive protein (CRP) levels.

Monoclonal Insulin Autoimmune Syndrome Successfully Treated With Plasma Cell Directed Therapy.

Background: Monoclonal insulin autoimmune syndrome (IAS) is a very rare disease characterized by severe attacks of hypoglycemia caused by circulating anti-insulin antibodies produced by a B-cell clone, usually clonal plasma cells.

Method: We present 2 female Norwegian patients with monoclonal IAS. The anti-insulin antibodies were quantified by immune precipitation and characterized using a 3-step manual in-house assay.

The Prevalence and Rate of Undiagnosed Celiac Disease in an Adult General Population, the Trøndelag Health Study, Norway.

Background & Aims: This study aimed to determine the total prevalence of celiac disease (CeD), including undiagnosed cases, in a population-based study of adults screened for CeD.

Methods: The study used the fourth Trøndelag Health Study (HUNT4), conducted in 2017-2019, where 56,042 adult (aged >20 years) residents of Nord-Trøndelag County, Norway, participated. Serum samples from 54,505 participants were analyzed for anti-transglutaminase 2 IgA and IgG.

Managing hemolysis in serum neuron-specific enolase measurements - an automated algorithm for routine practice.

Neuron-specific enolase (NSE) derived from neurons and peripheral neuroendocrine cells is a biomarker for neuroendocrine tumors and for prognostication in comatose cardiac arrest survivors. However, as platelets and erythrocytes contain NSE, hemolysis causes falsely elevated NSE. We used native serum and hemolysate derived from the same patients to make serial dilutions, and subsequently measured NSE (mNSE) and hemolytic index (HI) in each dilution.

Subcutaneous Vedolizumab Treatment in a Real-World Inflammatory Bowel Disease Cohort Switched From Intravenous Vedolizumab: Eighteen-Month Prospective Follow-up Study.

Background: Vedolizumab has since 2021 been available as a subcutaneous formulation. We aimed to assess 18-month drug persistence and possible predictive factors associated with discontinuation, safety, serum drug profile, drug dosing, and disease activity in a real-world cohort of patients with inflammatory bowel disease switched from intravenous to subcutaneous vedolizumab maintenance treatment.

Methods: Eligible patients were switched to subcutaneous vedolizumab and followed for 18 months or until discontinuation of subcutaneous treatment.

Clinical consequences of infliximab immunogenicity and the effect of proactive therapeutic drug monitoring: exploratory analyses of the randomised, controlled NOR-DRUM trials.

Background: Antidrug antibodies to TNF inhibitors might affect clinical outcomes. Proactive therapeutic drug monitoring allows for early detection of antidrug antibodies and might reduce negative clinical consequences. We aimed to explore how antidrug antibodies to the TNF inhibitor infliximab influence treatment outcomes, and to assess the effect of proactive therapeutic drug monitoring.

Coeliac disease in the Trøndelag Health Study (HUNT), Norway, a population-based cohort of coeliac disease patients.

Purpose: Coeliac disease (CD) is a common disorder and affects about 1% of the population worldwide. CD in the Trøndelag Health Study (HUNT) is a population-based cohort study which was established to provide new knowledge about CD that can improve the diagnostics and management, prevent the onset or progression and expand the knowledge about the role of genetics of the disease.

Participants: The cohort is based on the fourth wave of the population-based HUNT study (HUNT4), Norway, performed during 2017-2019, also including linkage to hospital records and the Norwegian Patient Registry (NPR).

Insulin autoimmune syndrome: not just one but two different diseases with therapeutic implications.

Summary: We present a young woman with treatment resistant insulin autoimmune syndrome (IAS) with a protracted course. Her serum insulin level was 6945 pmol/l (<160), C-peptide 4042 pmol/L (<1480), anti-insulin antibodies 5305 U/mL (<0.4) were monoclonal IgG kappa.

HLA-DQ2 is associated with anti-drug antibody formation to infliximab in patients with immune-mediated inflammatory diseases.

Background: Immunogenicity to tumour necrosis factor inhibitors is a significant clinical problem leading to treatment failure and adverse events. The study aimed to assess human leukocyte antigen (HLA) associations with anti-drug antibody (ADAb) formation to infliximab.

Methods: Immune-mediated inflammatory disease patients on infliximab therapy (n = 612) were included.

Switching from intravenous to subcutaneous vedolizumab maintenance treatment in patients with inflammatory bowel disease followed by therapeutic drug monitoring.

Objective: Vedolizumab (VDZ) for subcutaneous (SC) administration has recently become available. We aimed to assess feasibility, safety and clinical outcome when switching from intravenous (IV) to SC VDZ maintenance treatment in a real world cohort of patients with inflammatory bowel disease (IBD) followed by therapeutic drug monitoring (TDM).

Methods: Eligible IBD patients were switched from IV to SC treatment and assessed six months prior to switch, at baseline and six, twelve and twenty-six weeks after switch.

Humoral immune response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease on immunosuppressive medication: association to serum drug levels and disease type.

Objectives: Immune responses following SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) are not well characterized. The aims of this study were to explore the serological response associated with IBD, and immunosuppressive medications including serum concentrations of biologics and thiopurine metabolites.

Materials And Methods: This prospective, observational study included adult patients with ulcerative colitis (UC) and Crohn's disease (CD), and healthy controls.

The development and validation of a high-capacity serological assay for celiac disease.

Background: The aim of the present study was to develop and clinically validate a high-throughput assay for serum IgA and IgG antibodies against transglutaminase-2 (TG2) and to determine appropriate assay cut-offs for large-scale population screening for celiac disease.

Method: An automated method was developed using dual label time-resolved fluorometry on the AutoDELFIA platform. Individuals (n = 1920) from the general population were screened.

Risk factors for anti-drug antibody formation to infliximab: Secondary analyses of a randomised controlled trial.

Background: Anti-drug antibodies (ADAb) frequently form early in the treatment course of infliximab and other tumour necrosis factor (TNF) inhibitors, leading to treatment failure and adverse events.

Objective: To identify risk factors for ADAb in the early phase of infliximab treatment.

Methods: Patients (n = 410) with immune-mediated inflammatory diseases who initiated infliximab treatment were included in the 38-week Norwegian Drug Monitoring Trial (NOR-DRUM) A and randomised 1:1 to therapeutic drug monitoring (TDM) or standard therapy.

Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial.

Importance: Proactive therapeutic drug monitoring (TDM), consisting of individualized treatment based on scheduled assessments of serum drug levels, has been proposed as an alternative to standard therapy to optimize efficacy and safety of infliximab and other biologic drugs. However, it remains unclear whether proactive TDM improves clinical outcomes during maintenance therapy.

Objective: To assess whether proactive TDM during maintenance therapy with infliximab improves treatment efficacy by preventing disease worsening compared with standard infliximab therapy without TDM.

Serum etanercept concentrations in relation to disease activity and treatment response assessed by ultrasound, biomarkers and clinical disease activity scores: results from a prospective observational study of patients with rheumatoid arthritis.

Objectives: To identify the therapeutic range for etanercept and to assess the incidence of anti-etanercept antibody formation.

Methods: Associations between etanercept serum concentration and disease activity as well as treatment response were examined in a longitudinal observational study of rheumatoid arthritis patients starting etanercept. Disease activity was assessed by ultrasound (grey scale and power Doppler), 28-joint Disease Activity Score (DAS28), Simplified Disease Activity Index, plasma calprotectin and C reactive protein.