Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF-inhibitor: results from 13 European registries.

OBJECTIVES In bio-naïve patients with Psoriatic arthritis (PsA) initiating a Tumour Necrosis Factor inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes, were defined as common predictors. RESULTS In the pooled cohort (n = 13 369), six-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6,954, n = 5,275 and n = 13 369, respectively). Baseline predictors of remission, moderate response and 12-month drug retention were identified, five common across all three outcomes. Odds ratios (95% confidence interval) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (10 vs ≤ 10 mg/l: 1.52 (1.22-1.89) and one mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION Baseline predictors of remission, response and adherence to TNFi were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalisable from the country- to disease-level

Protection against LPS-induced cartilage inflammation and degradation provided by a biological extract of Mentha spicata

<p>Abstract</p> <p>Background</p> <p>A variety of mint [<it>Mentha spicata</it>] has been bred which over-expresses Rosmarinic acid (RA) by approximately 20-fold. RA has demonstrated significant anti-inflammatory activity <it>in vitro </it>and in small rodents; thus it was hypothesized that this plant would demonstrate significant anti-inflammatory activity <it>in vitro</it>. The objectives of this study were: a) to develop an <it>in vitro </it>extraction procedure which mimics digestion and hepatic metabolism, b) to compare anti-inflammatory properties of High-Rosmarinic-Acid <it>Mentha spicata </it>(HRAM) with wild-type control <it>M. spicata </it>(CM), and c) to quantify the relative contributions of RA and three of its hepatic metabolites [ferulic acid (FA), caffeic acid (CA), coumaric acid (CO)] to anti-inflammatory activity of HRAM.</p> <p>Methods</p> <p>HRAM and CM were incubated in simulated gastric and intestinal fluid, liver microsomes (from male rat) and NADPH. Concentrations of RA, CA, CO, and FA in simulated digest of HRAM (HRAM_sim) and CM (CM_sim) were determined (HPLC) and compared with concentrations in aqueous extracts of HRAM and CM. Cartilage explants (porcine) were cultured with LPS (0 or 3 μg/mL) and test article [HRAM_sim(0, 8, 40, 80, 240, or 400 μg/mL), or CM_sim(0, 1, 5 or 10 mg/mL), or RA (0.640 μg/mL), or CA (0.384 μg/mL), or CO (0.057 μg/mL) or FA (0.038 μg/mL)] for 96 h. Media samples were analyzed for prostaglandin E₂(PGE₂), interleukin 1β (IL-1), glycosaminoglycan (GAG), nitric oxide (NO) and cell viability (differential live-dead cell staining).</p> <p>Results</p> <p>RA concentration of HRAM_simand CM_simwas 49.3 and 0.4 μg/mL, respectively. CA, FA and CO were identified in HRAM_simbut not in aqueous extract of HRAM. HRAM_sim(≥ 8 μg/mL) inhibited LPS-induced PGE₂and NO; HRAM_sim(≥ 80 μg/mL) inhibited LPS-induced GAG release. RA inhibited LPS-induced GAG release. No anti-inflammatory or chondroprotective effects of RA metabolites on cartilage explants were identified.</p> <p>Conclusions</p> <p>Our biological extraction procedure produces a substance which is similar in composition to post-hepatic products. HRAM_simis an effective inhibitor of LPS-induced inflammation in cartilage explants, and effects are primarily independent of RA. Further research is needed to identify bioactive phytochemical(s) in HRAM_sim.</p

Author&apos;s personal copy Au implantation into various types of silicate glasses

a b s t r a c t The implantation of gold ions into three types of silicate glass was studied. The energies of the implanted Au + ions were 1701 keV, and the fluences of the ions were 1 Â 10 14 , 1 Â 10 15 , 3 Â 10 15 and 1 Â 10 16 cm À2 . The as-implanted samples were annealed in air at two temperatures (400 and 600°C). The Au concentration depth profiles were investigated using Rutherford Backscattering Spectrometry (RBS) and compared to simulated profiles from the SRIM. The structural changes were studied by UV-vis absorption spectroscopy. The obtained mono-mode waveguides were characterised using Dark Mode Spectroscopy at 671 nm to yield information on the refractive index changes. The results showed interesting differences depending on the type of glass and the post-implantation treatment. The obtained data were evaluated on the basis of the structure of the glass matrix, and the relations between the structural changes, waveguide properties and absorption, which are important for photonics applications, were formulated

Sex differences in the effectiveness of first-line tumor necrosis factor inhibitors in psoriatic arthritis; results from the EuroSpA Research Collaboration Network.

OBJECTIVE Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. METHODS Data from PsA patients across 13 EuroSpA registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response, using low disease activity (LDA) according to DAS28-CRP (<3.2) at 6 months as the primary outcome. Analyses were adjusted for age, country, csDMARD use, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimators. RESULTS We analyzed the treatment response of 7,679 PsA patients (50% women) with available data on LDA at 6 months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs. men, 4.4 [SD 1.2] vs. 4.2 [1.2]), though patient-reported outcome measures were worse in women. At 6 months, 64% of women and 78% of men had LDA (relative risk, 0.82; 95% confidence interval, 0.80 to 0.84). This difference was similar after adjustment (0.83; 0.81 to 0.85). TNFi retention rates were evaluated in 17,842 PsA patients. Women had significantly lower retention rates than men at all time points (women: 79%/64%/50% at 6/12/24 months versus men: 88%/77%/64%). CONCLUSION Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management