Safety of baricitinib in Japanese patients with rheumatoid arthritis in clinical use: 3-year data of all-case post-marketing surveillance study.

Objective: To assess safety of baricitinib in Japanese patients with rheumatoid arthritis in real-world clinical practice.

Methods: This all-case post-marketing surveillance study included patients initiating baricitinib for rheumatoid arthritis from September 2017 to April 2019. Treatment duration was recorded.

Safety and effectiveness of baricitinib for rheumatoid arthritis in Japanese clinical practice: 24-week results of all-case post-marketing surveillance.

Objectives: To assess the safety and effectiveness of baricitinib treatment for rheumatoid arthritis (RA) in real-world clinical practice.

Methods: This ongoing all-case post-marketing surveillance study (starting September 2017) includes all patients with RA treated with baricitinib in Japan. Safety and effectiveness (disease activity) were assessed for 24 weeks.

A novel risk score on admission for predicting death or need for surgery in patients with acute type A intramural hematoma receiving medical therapy.

There has been continuing discussion regarding the treatment strategy for acute type A intramural hematoma (IMH). Most patients are treated conservatively in Japan; hence, predicting fatal events and stratifying risks based on results normally obtained on hospital arrival are important. We aimed to examine the incidences and risk factors of death or need for surgery for acute type A IMH in patients receiving medical treatment and to identify high-risk patients using clinical findings on hospital arrival.

Longterm Safety of Tocilizumab: Results from 3 Years of Followup Postmarketing Surveillance of 5573 Patients with Rheumatoid Arthritis in Japan.

Objective: To evaluate the longterm safety of tocilizumab (TCZ) for the treatment of rheumatoid arthritis (RA) in a real-world clinical setting in Japan.

Methods: In this longterm extension of a single-arm, observational postmarketing surveillance study, a total of 5573 patients who initiated intravenous TCZ between April 2008 and July 2009 were observed for 3 years, regardless of its continuation, for incidence of fatal events, serious infections, malignancy, gastrointestinal perforations, and serious cardiac dysfunction.

Results: Of the 5573 patients who were enrolled, 4527 patients (81.

The risk of serious infection in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors decreased over time: a report from the registry of Japanese rheumatoid arthritis patients on biologics for long-term safety (REAL) database.

To investigate changes in the risk for serious infections (SIs) over time in Japanese rheumatoid arthritis (RA) patients treated with tumor necrosis factor inhibitors (TNFIs). This prospective cohort study included Japanese RA patients who began treatment with a TNFI from 2005 to 2007 (2005 group, n = 716, 634.2 patient years [PY]) and from 2008 to 2011 (2008 group, n = 352, 270.

Treatment strategy for reducing the risk of rituximab-induced cytokine release syndrome in patients with intravascular large B-cell lymphoma: a case report and review of the literature.

Introduction: Intravascular large B-cell lymphoma is a rare aggressive disseminated disease characterized by the presence of lymphoma cells in small vessels without lymphadenopathy. Rituximab, a novel monoclonal antibody against the CD20 B-cell antigen, has been reported to be effective in treating intravascular large B-cell lymphoma. However, adverse events have been reported in association with rituximab infusion.

A comparison of incidence and risk factors for serious adverse events in rheumatoid arthritis patients with etanercept or adalimumab in Korea and Japan.

Objective: To compare the incidence and risk factors of serious adverse events (SAEs) in rheumatoid arthritis (RA) patients treated with etanercept (ETN) or adalimumab (ADA) between Korean and Japanese registries.

Methods: We recruited 416 RA patients [505.2 patient-years (PYs)] who started ETN or ADA from Korean registry and 537 RA patients (762.

Drug retention rates and relevant risk factors for drug discontinuation due to adverse events in rheumatoid arthritis patients receiving anticytokine therapy with different target molecules.

Objective: To compare reasons for discontinuation and drug retention rates per reason among anticytokine therapies, infliximab, etanercept and tocilizumab, and the risk of discontinuation of biological agents due to adverse events (AE) in patients with rheumatoid arthritis (RA).

Method: This prospective cohort study included Japanese RA patients who started infliximab (n=412, 636.0 patient-years (PY)), etanercept (n=442, 765.

Time-dependent increased risk for serious infection from continuous use of tumor necrosis factor antagonists over three years in patients with rheumatoid arthritis.

Objective: To investigate associations between continuous treatments with tumor necrosis factor (TNF) antagonists and risk for developing serious infections (SIs) over 3 years in Japanese patients with rheumatoid arthritis (RA) enrolled in the Registry of Japanese RA Patients for Long-Term Safety (REAL) database.

Methods: We analyzed 727 RA patients who had started either infliximab or etanercept (the anti-TNF group; 1,480.1 patient-years [PY]) and 571 RA patients who had started conventional nonbiologic disease-modifying antirheumatic drugs (the unexposed group; 1,104.

Incidence and risk factors for serious infection in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors: a report from the Registry of Japanese Rheumatoid Arthritis Patients for Longterm Safety.

Objective: To compare tumor necrosis factor-α (TNF-α) inhibitors to nonbiological disease-modifying antirheumatic drugs (DMARD) for the risk of serious infection in Japanese patients with rheumatoid arthritis (RA).

Methods: Serious infections occurring within the first year of the observation period were examined using the records for patients recruited to the Registry of Japanese Rheumatoid Arthritis Patients for Longterm Safety (REAL), a hospital-based prospective cohort of patients with RA. The analysis included 1144 patients, 646 of whom were treated with either infliximab or etanercept [exposed group: 592.

[Falsely low MMP-3 by latex turbidimetric immunoassay].

We experienced a case with a falsely low value by a blood MMP-3 measuring reagent employing a recently structured new latex immunoturbidity. The case involved duplicate orders for one patient in a single day, and the blood collection amounts and measured values were approximately 6.0 mL and 206.

Chemokine receptor expression and functional effects of chemokines on B cells: implication in the pathogenesis of rheumatoid arthritis.

Introduction: Accumulation of B cells in the rheumatoid arthritis (RA) synovium has been reported, and it has been thought that these cells might contribute to the pathogenesis of RA by antigen presentation, autoantibody production, and/or inflammatory cytokine production. Chemokines could enhance the accumulation of B cells in the synovium. The aims of this study were to determine chemokine receptor expression by B cells both in the peripheral blood of normal donors and subjects with RA, and at the inflammatory site in RA, and the effects of chemokines on B cell activation.

Induction of pulmonary thromboembolism by neutrophil elastase in collagen-induced arthritis mice and effect of recombinant human soluble thrombomodulin.

We previously reported that during total knee arthroplasty in rheumatoid arthritis (RA) patients, the use of tourniquet might promote local release of neutrophil elastase (NE) from neutrophils, which may contribute to the development of pulmonary thromboembolism (PTE) and tissue injury. The aim of this study was to develop PTE by the use of NE in a mouse model of collagen-induced arthritis (CIA) and investigate the relationship between thrombus and endothelial cells as well as the effect of recombinant human soluble thrombomodulin (rhs-TM) in reducing the risk of PTE. Male DBA/1J mice were injected intracutaneously at several sites with an emulsion containing bovine collagen and later a booster shot to produce CIA mice.

Postoperative results and complications of total elbow arthroplasty in patients with rheumatoid arthritis: three types of nonconstrained arthroplasty.

Postoperative results and complications of total elbow arthroplasty (TEA) conducted for rheumatoid arthritis (RA) patients at our institute were studied. Primary TEAs were performed in 72 patients. The mean follow-up period was 3.

Involvement of TNF-like weak inducer of apoptosis in the pathogenesis of collagen-induced arthritis.

TNF-like weak inducer of apoptosis (TWEAK) is a type II membrane protein belonging to the TNF family that regulates apoptotic cell death, cellular proliferation, angiogenesis, and inflammation. However, the role of TWEAK in the pathogenesis of rheumatoid arthritis (RA) remains unclear. In this study, we have investigated the effect of neutralizing anti-TWEAK mAb on the development of collagen-induced arthritis (CIA), a well-established murine model of RA.

Application of cellular gene therapy for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by persistent inflammation of joints resulting in progressive destruction of cartilage and bone. Recently, biological agents that suppress the activities of proinflammatory cytokines have shown efficacy as antirheumatic drugs, but require frequent administration, and often result in systemic immune suppression. Thus, gene transfer approaches are being developed as an alternative approach for targeted, more efficient, and sustained delivery of inhibitors of inflammatory cytokines as well as other therapeutic agents.

Amelioration of bone loss in collagen-induced arthritis by neutralizing anti-RANKL monoclonal antibody.

Receptor activator of NF-kappaB (RANK) and its ligand (RANKL) are pivotal regulators of osteoclast differentiation. RANK and RANKL also mediate T cell/dendritic cell (DC) interaction. Previous study has shown that RANK/RANKL interaction induces prolonged DC survival and antigen presentation.

Modeling and cost-effectiveness analysis of etanercept in adults with rheumatoid arthritis in Japan: a preliminary analysis.

The tumor necrosis factor (TNF) antagonist etanercept is an antirheumatic agent which was approved by Japanese regulatory authorities in January 2005. In Japan, the cost-effectiveness of this therapy for patients with rheumatoid arthritis (RA) has not previously been evaluated. This study models the cost-utility of etanercept in comparison with standard therapy with disease-modifying antirheumatic drugs (DMARDs) among adult Japanese RA patients who have failed a previous course of the DMARD bucillamine.

Expression of membrane-bound and soluble receptor activator of NF-kappaB ligand (RANKL) in human T cells.

The receptor activator of NF-kappaB ligand (RANKL) and its receptor RANK are critical regulators for immune responses as well as bone remodeling. RANKL is a type II transmembrane protein that has two forms-a membrane-anchored protein and a secreted protein. In this report, we demonstrate for the first time the kinetical expression of two forms of RANKL in human T cells using two monoclonal antibodies (mAbs) against human RANKL, which we newly derived.

Adoptive cellular gene therapy of autoimmune disease.

Autoimmune disorders represent inappropriate immune responses directed at self-tissue. Because CD4+ T cells are important mediators in the pathogenesis of autoimmune disease, they are ideal candidates for cell-based gene therapy. Using retrovirally-transduced cells and luciferase bioluminescence, we have demonstrated that primary T cells and hybridomas, rapidly and preferentially home to the sites of inflammation in organ-specific autoimmune disease.

Retroviral gene therapy of collagen-induced arthritis by local delivery of IL-4.

Rheumatoid arthritis (RA) is an autoimmune arthritis, for which treatment options remain limited. This study investigated the potential role of adoptive cellular gene therapy as a novel means for treating the RA animal model collagen-induced arthritis (CIA). Adoptive transfer of antigen-specific T-cell hybridomas retrovirally transduced to express IL-4 1 day before booster immunization significantly reduced the number of inflamed joints.