Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study.

Introduction: Phosphodiesterase type 4 (PDE4) inhibition is a well-known anti-inflammatory mechanism. However, the clinical use of PDE4 inhibitors has been compromised by the occurrence of mechanism-associated adverse reactions, which often limit the maximum tolerated dose. To minimize systemic exposure, a topically active PDE4 inhibitor with low transdermal bioavailability could be clinically useful.

Safety, tolerability and pharmacokinetics of a novel phosphodiesterase inhibitor, E6005 ointment, in healthy volunteers and in patients with atopic dermatitis.

Objectives: The purpose of the present studies was to assess the safety, tolerability and pharmacokinetics of topical application of a novel phosphodiesterase inhibitor, E6005, in healthy volunteers and in patients with atopic dermatitis (AD).

Methods: In two randomized, investigator-blind, vehicle-controlled studies, we evaluated the topical application of E6005 ointment at concentrations ranging from 0.01% to 0.

Safety and efficacy of topical E6005, a phosphodiesterase 4 inhibitor, in Japanese adult patients with atopic dermatitis: results of a randomized, vehicle-controlled, multicenter clinical trial.

The safety and efficacy of topical E6005, a novel phosphodiesterase 4 inhibitor, in Japanese adults with atopic dermatitis were evaluated. A total of 78 patients were randomized to receive either the 0.2% E6005 ointment or vehicle control (without E6005) at an allocation ratio of 2:1.

Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial.

Objective: The aim of this study was to compare efficacy outcomes of initial treatment with adalimumab + MTX vs adalimumab addition following 26 weeks of MTX monotherapy in Japanese early RA patients naive to MTX with high disease activity.

Methods: Patients completing the 26-week, randomized, placebo-controlled trial of adalimumab + MTX were eligible to receive 26 weeks of open-label adalimumab + MTX. Patients were assessed for mean change from baseline in the 28-joint DAS with ESR (DAS28-ESR) and modified total Sharp score (mTSS), and for the proportions of patients achieving clinical, functional or radiographic remission.

Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study.

Objectives: To evaluate the efficacy and safety of adalimumab+methotrexate (MTX) in Japanese patients with early rheumatoid arthritis (RA) who had not previously received MTX or biologics.

Methods: This randomised, double-blind, placebo-controlled, multicentre study evaluated adalimumab 40 mg every other week+MTX 6-8 mg every week versus MTX 6-8 mg every week alone for 26 weeks in patients with RA (≤2-year duration). The primary endpoint was inhibition of radiographic progression (change (Δ) from baseline in modified total Sharp score (mTSS)) at week 26.

[Topics of glucocorticoids--centered on therapy for rheumatoid arthritis].

Glucocorticoids (steroids) have been widely used for the treatment of patients with rheumatoid arthritis (RA) since Hench had attempted to administer cortisone (Kendall's compound E) to an active RA patient in 1948. Rheumatologists even in the 21st century can learn a lot from the history of steroid. In this feature article on steroid, a brief outline of 11β-hydroxysteroid dehydrogenase type 1, a tissue-specific regulator of steroid response, is presented.

[RANKL inhibition as therapy for joint damage].

RANK ligand (RANKL) is a key mediator of osteoclast formation, function, and survival. Therefore, RANKL is thought to be responsible for osteoclast-mediated bone resorption in a broad range of disorders such as postmenopausal osteoporosis and cancer-induced bone disease. Moreover, RANKL has been implicated as a primary mediator of bone erosions, a hallmark of rheumatoid arthritis (RA).

[Antibody to IL-1 or IL-15].

There have recently been fewer publications written in Japanese describing inflammatory cytokines in rheumatoid arthritis (RA) other than tumor necrosis factor and interleukin (IL) -6. Interleukins such as IL-1 and IL-15 are thought to play an important role, at least in part, in pathogenesis of RA. In this review, the two interleukins above were mentioned from mainly RA point of view, respectively.

One third of Japanese patients with rheumatoid arthritis use complementary and alternative medicine.

We investigated the prevalence and predictors of complementary and alternative medicine (CAM) use by patients with rheumatoid arthritis (RA) in Japan. A cross-sectional descriptive study was performed using the database from a large observational cohort of RA patients in the Institute of Rheumatology, Tokyo Women's Medical University. Logistic regression analysis was carried out to reveal predictive factors for CAM use.

Suppression of adjuvant-induced arthritic bone destruction by cyclooxygenase-2 selective agents with and without inhibitory potency against carbonic anhydrase II.

Unlabelled: In vitro assays revealed that COX-2 inhibitors with CA II inhibitory potency suppressed both differentiation and activity of osteoclasts, whereas that without the potency reduced only osteoclast differentiation. However, all COX-2 inhibitors similarly suppressed bone destruction in adjuvant-induced arthritic rats, indicating that suppression of osteoclast differentiation is more effective than that of osteoclast activity for the treatment.

Introduction: Cyclooxygenase (COX)-2 and carbonic anhydrase II (CA II) are known to play important roles in the differentiation of osteoclasts and the activity of mature osteoclasts, respectively.

A new syndrome: multiple dislocations of distal interphalangeal joints associated with interstitial pneumonia, Sjögren's syndrome, and positive autoantibodies.

Abstract  A 54-year-old woman and a 64-year-old man consulted our clinic for dislocation of the distal interphalangeal (DIP) joints. They both had been diagnosed as having Sjögren's syndrome. In addition, interstitial pneumonia had been detected several years earlier in both cases.

[Pharmacogenetics of disease modifying anti-rheumatic drugs].

There are large differences in the effectiveness of disease modifying anti-rheumatic drugs(DMARD) from one person to the next. Adverse drug reactions caused by DMARD can also occur to some patients, but do not occur to others. One possible cause of the differences in the effectiveness and adverse drug reactions is genetic variation in how individuals metabolize drugs.

Polymorphisms in the methylenetetrahydrofolate reductase gene were associated with both the efficacy and the toxicity of methotrexate used for the treatment of rheumatoid arthritis, as evidenced by single locus and haplotype analyses.

5,10-Methylenetetrahydrofolate reductase (MTHFR), a key enzyme involved in folate metabolism, has two common polymorphisms that affect enzyme activity. The objective of this study was to examine whether there was a correlation between the genotype or haplotype of the MTHFR gene and the efficacy or toxicity of methotrexate (MTX) in the treatment of rheumatoid arthritis. MTX-treated rheumatoid arthritis patients (n = 106) were selected from outpatient clinics and used for a retrospective study to examine the correlation between genotypes or haplotypes concerning polymorphisms of the MTHFR gene, and the efficacy or toxicity of MTX.