Real-world experience with filgotinib for rheumatoid arthritis in Germany : A retrospective chart review.

Background: Real-world data for filgotinib, a Janus kinase (JAK)1 inhibitor, are limited in patients with rheumatoid arthritis (RA).

Objectives: To explore real-world filgotinib use in patients with RA in Germany.

Materials And Methods: This retrospective chart review included patients aged ≥ 18 years with confirmed moderate to severe RA who initiated filgotinib before December 1, 2021, with ≥ 6 months of medical records available prior to filgotinib initiation or after initial diagnosis.

Effect of Filgotinib on Body Mass Index (BMI) and Effect of Baseline BMI on the Efficacy and Safety of Filgotinib in Rheumatoid Arthritis.

Introduction: This post hoc analysis of the phase 3 rheumatoid arthritis (RA) filgotinib clinical trial program assessed the effect of filgotinib on body mass index (BMI) in patients with RA and the impact of BMI on the efficacy and safety of filgotinib.

Methods: FINCH 1-3 were randomized, double-blind, active- or placebo-controlled phase 3 trials of filgotinib 100 and 200 mg in patients with RA (N = 3452). BMI assessments included the mean change from baseline in BMI and the proportion of patients whose BMI increased by incremental thresholds.

Real-world treatment persistence in patients with rheumatoid arthritis initiating DMARDs in Germany-a health insurance claims data analysis.

Objective: To investigate treatment patterns in patients with rheumatoid arthritis (RA) in Germany who had previously received conventional synthetic (cs) or biologic (b) disease-modifying antirheumatic drugs (DMARDs).

Methods: Patients with RA who initiated treatment with a csDMARD, bDMARD, or Janus kinase (JAK) inhibitor between 2017 and 2018 and who had previously received csDMARD or bDMARD therapy were retrospectively selected from the Institute for Applied Health Research Berlin GmbH (InGef). Time on treatment and discontinuation risk were assessed using the Kaplan-Meier method.

Persistence with Biologic Treatment in Patients with Inflammatory Bowel Disease: A German Claims Data Analysis.

Objectives: This study aimed to assess the real-world rates of treatment discontinuation and switching of biologic therapies in patients with inflammatory bowel disease (IBD).

Methods: A retrospective claims data analysis on all continuously insured adult IBD patients with initiation of a biologic therapy was conducted. Observation started with the date of the first prescription of index tumor necrosis factor α-inhibitors (anti-TNFα) or vedolizumab (VDZ) therapy and lasted 12 months.

Real-world biologic treatment and associated cost in patients with inflammatory bowel disease.

Objectives:  This study aimed to describe biologic treatment of German inflammatory bowel disease (IBD) patients, including biologics' dosage, health care resource use, and treatment-associated cost.

Methods:  In this retrospective claims data analysis, all continuously insured adult IBD patients (Crohn's disease [CD] or ulcerative colitis [UC]) who started a new therapy with an anti-tumor necrosis factor alpha (anti-TNF-α) or vedolizumab (VDZ) were included. Observation started with the date of the first prescription of index biologic therapy and lasted 12 months.

Flupirtine-induced liver injury--seven cases from the Berlin Case-control Surveillance Study and review of the German spontaneous adverse drug reaction reporting database.

Purpose: The hepatotoxic potential of the analgesic flupirtine has attracted increased attention over the past years. Recently, risk minimisation measures such as maximum treatment duration of 2 weeks have been requested by the European Medicines Agency (EMA). This study was conducted to further elucidate the clinical pattern of flupirtine-induced liver injury (FILI).

A natural fiber complex reduces body weight in the overweight and obese: a double-blind, randomized, placebo-controlled study.

Objective: A proprietary natural fiber complex (Litramine IQP G-002AS) derived from Opuntia ficus-indica, and standardized on lipophilic activity, was previously shown in preclinical and human studies to reduce dietary fat absorption through gastrointestinal (GI) fat binding. Here, we investigated the efficacy and safety of IQP G-002AS in body weight reduction.

Design And Methods: One hundred twenty-five overweight and obese adults participated in the study.

S3 - Guidelines on the treatment of psoriasis vulgaris (English version). Update.

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5% to 2%.

The extracellular regulated kinase-1 (ERK1) controls regulated alpha-secretase-mediated processing, promoter transactivation, and mRNA levels of the cellular prion protein.

The α-secretases A disintegrin and metalloprotease 10 (ADAM10) and ADAM17 trigger constitutive and regulated processing of the cellular prion protein (PrP(c)) yielding N1 fragment. The latter depends on protein kinase C (PKC)-coupled M1/M3 muscarinic receptor activation and subsequent phosphorylation of ADAM17 on its intracytoplasmic threonine 735. Here we show that regulated PrP(c) processing and ADAM17 phosphorylation and activation are controlled by the extracellular-regulated kinase-1/MAP-ERK kinase (ERK1/MEK) cascade.

Short-term treatment with a beta-blocker with vasodilative capacities improves intrarenal endothelial function in experimental renal failure.

Aims: In patients with renal disease the cardiovascular risk is greatly increased, and endothelial dysfunction is assumed to play a pivotal role in this process. Therefore we compared treatment effects of a beta-blocker with additional vasodilatory capacities (nebivolol) and a beta-blocker lacking these actions (metoprolol) on intrarenal and coronary vascular function in a rat model of renal failure with hypertension.

Main Methods: Renal failure was induced by 5/6-nephrectomy (Nx) and analyzed after 4 weeks in Wistar rats.

Single low-dose administration of pharmacological inhibitor of mitogen-activated ERK kinase to the adventitia of the injured rat carotid artery suppresses neointima formation and inhibits nuclear ERK signaling.

Arterial injury has been reported to activate the mitogen-activated ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. Pharmacological MEK inhibition was previously shown to inhibit injury-induced neointima formation in rodent models, but inhibitor compounds were administered either locally at a high dose or systemic treatment was performed over an extended period of time. Aim of this study was, therefore, to explore the efficiency of single low-dose administration of the MEK inhibitor PD98059 on neointima formation in the injured rat carotid artery.

p53-Dependent transcriptional control of cellular prion by presenilins.

The presenilin-dependent gamma-secretase processing of the beta-amyloid precursor protein (betaAPP) conditions the length of the amyloid beta peptides (Abeta) that accumulate in the senile plaques of Alzheimer's disease-affected brains. This, together with an additional presenilin-mediated epsilon-secretase cleavage, generates intracellular betaAPP-derived fragments named amyloid intracellular domains (AICDs) that regulate the transcription of several genes. We establish that presenilins control the transcription of cellular prion protein (PrP(c)) by a gamma-secretase inhibitor-sensitive and AICD-mediated process.

Evidence-based (S3) guidelines for the treatment of psoriasis vulgaris.

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1 to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life.

Genomic organisation of the mouse gene encoding endothelin-converting enzyme-1 (ECE-1) and mRNA expression of ECE-1 isoforms in murine tissues.

Mouse knockout-models have previously revealed important biological functions of endothelin-converting enzyme-1 (ECE-1) in normal cardiac and craniofacial development. Since human ECE-1 is expressed in various isoforms, termed a, b, c, and d, expression of which is controlled by alternative promoters, we postulated that corresponding isoforms may also be transcribed from the murine Ece1 gene. By comparative sequence analysis using exon-specific sequences of human and rat ECE-1 we have resolved the complete exon-intron structure of the murine Ece1 locus on chromosome 4.

Inverse regulation of preproendothelin-1 and endothelin-converting enzyme-1beta genes in cardiac cells by mechanical load.

Mechanical stretch and para- and/or autocrine factors, including endothelin-1, induce hypertrophy of cardiac myocytes and proliferation of fibroblasts. To investigate the effect of mechanical load on endothelin-1 production and endothelin system gene expression in neonatal rat ventricular myocytes and fibroblasts, we exposed cells to cyclic mechanical stretch in vitro (0.5 Hz, 10-25% elongation, from 1 min to 24 h).

Regulation of the major isoform of human endothelin-converting enzyme-1 by a strong housekeeping promoter modulated by polymorphic microsatellites.

Background: Human endothelin-converting enzyme (ECE)-1, the key enzyme in endothelin biosynthesis, shows broad cell and tissue expression within the cardiovascular system. Expression of ECE-1c, which represents the major ECE-1 isoform, is directed by an alternative promoter, but the mechanisms of ECE-1c promoter regulation are largely unknown. As ECE-1c transcription is initiated from several start sites, we hypothesized that the ECE-1c promoter functions as a housekeeping promoter.

Differential regulation of in vivo angiogenesis by angiotensin II receptors.

Angiotensin II (ANG II), a key regulator of blood pressure and body fluid homeostasis, exerts mitogenic effects on endothelial cells. We therefore hypothesized that ANG II could be a mediator between homeostatic changes within the vascular perfusion bed and growth factor-driven angiogenesis. In the present study, we applied the alginate implant angiogenesis model in mice with normal ANG II levels, elevated ANG II levels by transgenic overexpression of angiotensinogen (AOGEN), or in AT2 receptor-deficient mice.

Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis.

Background: Angioplasty stimulates proliferation and migration of vascular smooth muscle cells (VSMC), leading to neointimal thickening and vascular restenosis. In a rat model of balloon catheter injury (BCI), we investigated whether alterations in expression of Ca2+-activated K+ channels (KCa) contribute to intimal hyperplasia and vascular restenosis.

Methods And Results: Function and expression of KCa in mature medial and neointimal VSMC were characterized in situ by combined single-cell RT-PCR and patch-clamp analysis.