The Biologic IRL201805 Alters Immune Tolerance Leading to Prolonged Pharmacodynamics and Efficacy in Rheumatoid Arthritis Patients.

A homologue of binding immunoglobulin protein/BiP-IRL201805 alters the function of immune cells in pre-clinical in vivo and in vitro studies. The aim of the study was to select biomarkers that clearly delineate between RA patients who respond to IRL201805 and placebo patients and reveal the immunological mode of action of IRL201805 driving the extended pharmacodynamics observed in responding patients. Biomarkers that distinguished between responding patients and placebo patients included downregulation of serum interferon-γ and IL-1β; upregulation of anti-inflammatory mediators, serum soluble CTLA-4, and intracellular monocyte expression of IDO; and sustained increased CD39 expression on CD3CD4CD25 CD127 regulatory T cells.

Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction.

Background: Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y-inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry).

Methods: In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days.

Results: Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin.

Binding Immunoglobulin Protein (BIP) Inhibits TNF-α-Induced Osteoclast Differentiation and Systemic Bone Loss in an Erosive Arthritis Model.

Objective: The association between inflammation and dysregulated bone remodeling is apparent in rheumatoid arthritis and is recapitulated in the human tumor necrosis factor transgenic (tg) mouse model. We investigated whether extracellular binding immunoglobulin protein (BiP) would protect the tg mouse from both inflammatory arthritis as well as extensive systemic bone loss and whether BiP had direct antiosteoclast properties in vitro.

Methods: tg mice received a single intraperitoneal administration of BiP at onset of arthritis.

Real world long-term impact of intensive treatment on disease activity, disability and health-related quality of life in rheumatoid arthritis.

Background: The emphasis on treating rheumatoid arthritis (RA) intensively reduces disease activity but its impact in routine care is uncertain. We evaluated temporal changes in disease activities and outcomes in a 10-year prospective observational cohort study of patients in routine care at one unit.

Methods: The Guy's and St Thomas' RA cohort was established in 2005.

The frequency of remission and low disease activity in patients with rheumatoid arthritis, and their ability to identify people with low disability and normal quality of life.

Objective: Treat-to-target in rheumatoid arthritis (RA) recommends targeting remission, with low disease activity (LDA) being an alternative goal. When deciding to target remission or LDA, important considerations are the likelihood of attaining them, and their impacts on function and health-related quality of life (HRQoL). We have addressed this by studying: (a) the frequency of remission and LDA/remission; (b) DAS28-ESR trends after remission; (c) ability of remission vs.