Comparison of joint destruction between standard- and low-dose etanercept in rheumatoid arthritis from the Prevention of Cartilage Destruction by Etanercept (PRECEPT) study.

OBJECTIVE: To evaluate the prevention of joint destruction and clinical efficacy of low-dose etanercept (ETN) (25 mg/week) compared with standard-dose ETN (50 mg/week) in RA. METHODS: In this prospective, randomized, open-label study, 70 patients were assigned to receive ETN at either 50 or 25 mg/week for 52 weeks. The primary endpoint was the variation in modified total Sharp score (mTSS), and secondary endpoints were variations in disease activity score in 28 joints (DAS-28), modified HAQ and adverse event rate. Values of mTSS were calculated at baseline and after 52 weeks. Non-progression was estimated as ΔmTSS ≤0.5, and the non-progression rate was compared between groups. RESULTS: Mean values at baseline were as follows: disease duration 9.2 years; DAS-28 5.45; and annual progression of mTSS 26.1. No significant differences in background were seen between groups. At 52 weeks, the non-progression rate was significantly less in the 25 mg/week group (36.7%) than in the 50 mg/week group (67.7%) (P = 0.041). Mean ΔmTSS was higher at 25 mg/week (1.03) than at 50 mg/week (-0.13). DAS-28 was significantly improved at 4 weeks, and the effect of treatment lasted for 52 weeks in both groups. No differences in adverse event rates were seen between groups. CONCLUSION: Low-dose ETN is not inferior to standard-dose ETN in terms of effects on clinical manifestations. However, in terms of the radiographic non-progression rate, the effects of low-dose ETN may be inferior to the effects of standard-dose ETN. TRIAL REGISTRATION: UMIN Clinical Trials Registry, http://www.umin.ac.jp/ctr/, UMIN000001798.

Clinical and radiologic analysis of on-demand use of etanercept for disease flares in patients with rheumatoid arthritis for 2 years: The RESUME study: A case-control study.

To reduce costs of biological disease-modifying antirheumatic drugs (bDMARDs), we evaluated the efficacy of repeated etanercept (ETN) discontinuation and restarting in rheumatoid arthritis (RA) patients in a case-control study.Thirty-one bDMARD-naive RA patients with moderate to high disease activity received ETN until low disease activity (LDA) was achieved, after which ETN was discontinued. Upon flaring, ETN was readministered with observation every 2 months for 2 years, and radiographically evaluated in comparison with a historical control group treated continuously with ETN. Statistical methods including Fisher exact test, analysis of variance (ANOVA), Kruskal-Wallis test, multiple regression analysis, and Student t test were conducted as appropriate.Thirteen patients with inadequate response to ETN were withdrawn from the study, and 5 had no flare-up after ETN discontinuation. In the remaining 13 patients, ETN was used on-demand to maintain LDA. Multivariate analysis revealed that MTX was significantly correlated with ETN. All 13 patients achieved LDA at final follow-up. Although joint damage progressed in patients using ETN on-demand, structural damage progression in the on-demand group was not significantly different from that in controls.On-demand use of ETN for flaring reduced disease activity but not structural damage in 50% of patients (though not significantly). However, inhibition of joint damage was achieved in 50% of patients after 2 years, supporting on-demand use of ETN as a treatment option for patients with RA who cannot afford bDMARD or targeted synthetic DMARD therapy.

Development of antimicrobial thermoplastic material from archaeal poly-γ-L-glutamate and its nanofabrication.

Here we describe a stoichiometric ion-complex of archaeal poly-γ-L-glutamate (L-PGA) and hexadecylpyridinium cation (HDP(+)), called PGAIC, which shows remarkable chemical resistance and potential as a novel functional thermoplastic. PGAIC films suppressed the proliferation of prokaryotic (Escherichia coli, Bacillus subtilis, Salmonella typhimurium, and Staphylococcus aureus) and eukaryotic (Saccharomyces cerevisiae) microorganisms. Moreover, its antifungal activity was demonstrated against a prevalent species of Candida (Candida albicans) and a filamentous fungus (Aspergillus niger). The minimal inhibitory concentrations were estimated as 0.25 mg mL(-1), and zones of growth inhibition appeared when PGAIC-coated polyethylene terephthalate (PET) films were placed in culture plates, whereas PET had very little effect on fungal growth. Soluble PGAIC thus shows promises as an antimicrobial and as a coating substrate. We also succeeded in synthesizing an L-PGA-based nanofiber using an ethanol solution of PGAIC.