Serum-soluble folate receptor β as a biomarker for the activity of rheumatoid arthritis synovitis and the response to anti-TNF agents.

This study aims to develop a sandwich ELISA system for the measurement of soluble folate receptor β (sFRβ) and evaluate whether base line levels of serum sFRβ are a biomarker for the activity of RA synovitis and the response to anti-TNF agents. Serum sFRβ from normal controls (41 samples), patients with OA (29 samples), and patients with RA (27 samples) and synovial fluid sFRβ from patients with RA (17 samples) were measured by sandwich ELISA, using anti-FRαβ and anti-FRβ antibodies as capture and detection antibodies, respectively. Baseline levels of serum sFRβ before therapy were evaluated in relation with DAS28-CRP or CRP and response to anti-TNF agents at 3-month follow-up.

Risk of low bone mineral density in patients with rheumatoid arthritis treated with biologics.

Background: Osteoporosis is a complication of rheumatoid arthritis (RA). We identified risk factors for osteoporosis during treatment with biologics.

Methods: Femoral neck bone mineral density (BMD) was measured in 186 patients with biologics-treated RA.

An investigation of the correlation between blood concentration of mizoribine and its efficacy in treatment of rheumatoid arthritis based on indices of drug survival and improvement in DAS28-CRP.

Objectives: The efficacy of mizoribine (MZR) in treatment of rheumatoid arthritis (RA) was retrospectively investigated in terms of drug survival, improvement in Disease Activity Score-28 (DAS28)-C-reactive protein (CRP), and blood MZR concentration obtained 3 h after dosing (MZR-C3).

Methods: To compare the efficacy of MZR administered via different regimens, the subjects were divided into 2 groups: those receiving a single dose of MZR at 100-150 mg every other day (group A) and those receiving 2 or 3 divided doses of the drug on consecutive days, which is the usual dosing method of the drug (group B).

Results: Group A had significantly higher MZR-C3 levels compared with group B, as well as significantly greater improvement in DAS28-CRP.

Assessment of peripheral blood CD4+ adenosine triphosphate activity in patients with rheumatoid arthritis.

Objective: The ability of the ImmuKnow (Cylex) assay to predict the risk of infection in rheumatoid arthritis (RA) patients receiving synthetic or biological disease-modifying antirheumatic drugs (DMARDs) was examined.

Methods: The amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin was measured in whole blood from 117 RA patients without infection versus 17 RA patients with infection, and compared with results in 75 healthy controls.

Results: The mean ATP level was significantly lower in patients with infection compared to both healthy controls (P < 0.

Factors associated with fatal outcome of leflunomide-induced lung injury in Japanese patients with rheumatoid arthritis.

Objective: To elucidate the factors associated with poor prognosis of LEF-induced lung injury in patients with RA.

Methods: The background and clinical and laboratory features of LEF-induced lung injury were examined and compared between patients who died of and who recovered from it.

Results: Among 22 patients who developed LEF-induced lung injury, 9 died of and 13 recovered from it.

Leflunomide-induced interstitial lung disease: prevalence and risk factors in Japanese patients with rheumatoid arthritis.

Objectives: The possible link between LEF and interstitial lung disease (ILD) has evoked increasing concern. The aim of the present study was to elucidate the prevalence and risk factors for newly developed and/or exacerbated ILD, based on post-marketing surveillance data, in which all RA patients receiving LEF were pre-registered and monitored for 24 weeks in Japan.

Methods: We analysed data from a cohort of 5054 RA patients who were prescribed LEF since its launch in September 2003 in Japan.

Proposals for leflunomide use to avoid lung injury in patients with rheumatoid arthritis.

Among the 5,043 consecutive patients registered in the postmarketing surveillance for leflunomide, 61 were reported to have lung injury and 24 died from it. The adjusted multivariate logistic regression analysis of the risk factors showed that preexisting interstitial lung disease posed the greatest risk, as well as loading dose, smoking history, and low body weight of 40 kg or less with odds ratios of 8.17, 3.

[Effective combination therapy of TNF antagonists with DMARDs].

Efficacy and safety of anti-tumor necrosis factor (TNF) antagonists (infliximab, etanercept, adalimumab) in combination with methotrexate for rheumatoid arthritis is well determined. But methotrexate is not tolerable nor effective in some cases. Leflunomide in combination with anti-TNF antagonists is the alternative combination therapy in the world.

In vitro and in vivo efficacy of a recombinant immunotoxin against folate receptor beta on the activation and proliferation of rheumatoid arthritis synovial cells.

Objective: To investigate the effects of the recombinant immunotoxin dsFv anti-FRbeta-PE38, which consists of the disulfide-stabilized Fv fragment (dsFv) of the anti-folate receptor beta (anti-FRbeta) antibody and the 38-kd portion of Pseudomonas exotoxin A (PE38), on the activation and proliferation of cells that function in inflammatory and degradative processes in rheumatoid arthritis (RA) synovial tissue.

Methods: The Ig VH-PE38 fusion protein and the Ig VL protein were produced in Escherichia coli, and then joined with a disulfide bond by engineering cysteine residues in the framework regions of these proteins. The effects of dsFv anti-FRbeta-PE38 on the activation and proliferation of cells in RA synovial tissue were investigated by immunohistochemistry; the numbers of cells expressing CD68, vascular cell adhesion molecule 1, angiopoietin 1, CD34, proliferating cell nuclear antigen, and interleukin-6 and the numbers of apoptotic cells were counted in RA synovial tissue engrafted into SCID mice treated or not treated with dsFv anti-FRbeta-PE38.

Anti-interleukin-6 receptor antibody therapy favors adrenal androgen secretion in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled study.

Objective: Proinflammatory cytokines such as tumor necrosis factor (TNF) were demonstrated to inhibit adrenal steroidogenesis in patients with rheumatoid arthritis (RA), and this was particularly evident in the increase in adrenal androgen levels during anti-TNF therapy. This study investigated the influence on steroidogenesis of an interleukin-6 (IL-6)-neutralizing strategy using IL-6 receptor monoclonal antibodies (referred to as MRA).

Methods: In a placebo-controlled, double-blind, randomized study over 12 weeks in 29 patients with RA being treated with prednisolone, 13 of whom received placebo and 16 of whom received 8 mg MRA/kg body weight, the effects of MRA on serum levels of adrenocorticotropic hormone (ACTH), cortisol, 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione (ASD), estrone, and 17beta-estradiol, as well as their respective molar ratios, were determined.

Effectiveness of anti-folate receptor beta antibody conjugated with truncated Pseudomonas exotoxin in the targeting of rheumatoid arthritis synovial macrophages.

Objective: To define the distribution of folate receptor beta (FRbeta)-expressing cells in various tissues, including rheumatoid arthritis (RA) synovial tissues, and to verify the effects of an immunotoxin composed of an anti-FRbeta monoclonal antibody (mAb) and truncated Pseudomonas exotoxin A (PEA) on apoptosis and tumor necrosis factor alpha (TNFalpha) production by adherent synovial mononuclear cells from RA patients.

Methods: Anti-FRbeta mAb were produced by immunizing mice with FRbeta-transfected murine pre-B cells. The distribution of the FRbeta antigen was examined by immunohistochemical analysis using anti-FRbeta mAb and macrophage-specific anti-CD163 mAb.