52-week results of the phase 3 randomized study comparing SB4 with reference etanercept in patients with active rheumatoid arthritis

Objective: To compare the 52-week efficacy and safety of SB4 [an etanercept biosimilar] with reference etanercept (ETN) in patients with active RA. Methods: In a phase 3, randomized, double-blind, multicentre study, patients with moderate to severe RA despite MTX treatment were randomized to receive 50 mg/week of s.c. SB4 or ETN up to week 52. Efficacy assessments included ACR response rates, 28-joint DAS, Simplified and Clinical Disease Activity Indices and changes in the modified total Sharp score (mTSS). Safety and immunogenicity were also evaluated. Results: A total of 596 patients were randomized to receive either SB4 (n = 299) or ETN (n = 297) and 505 (84.7%) patients completed 52 weeks of the study. At week 52, the ACR20 response rates in the per-protocol set were comparable between SB4 (80.8%) and ETN (81.5%). All efficacy results were comparable between the two groups and they were maintained up to week 52. Radiographic progression was also comparable and the change from baseline in the mTSS was 0.45 for SB4 and 0.74 for ETN. The safety profile of SB4 was similar to that of ETN and the incidence of anti-drug antibody development up to week 52 was 1.0 and 13.2% in the SB4 and ETN groups, respectively. Conclusion: Efficacy including radiographic progression was comparable between SB4 and ETN up to week 52. SB4 was well tolerated and had a similar safety profile to that of ETN. Trial registration number: ClinicalTrials.gov NCT01895309, EudraCT 2012-005026-30

Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA Study

Introduction Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). Methods The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. Results Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P LT 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P LT 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies. Conclusions In this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself

A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy

Objectives: To compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. Methods: This is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured. Results: 596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was -9.41% to 4.98%, which is completely contained within the predefined equivalence margin of -15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%). Conclusions: SB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN

The Effects of Cannabis sativa L. Extract on Oxidative Stress Markers In Vivo

In recent decades, a lot of attention has been paid to Cannabis sativa L. due to its useful applications, including in fibers, oil, food for humans and animals, and therapeutics. The present study aimed to determine antioxidant activity of cannabinoids in Cannabis sativa L. in vivo, evaluating the possible antioxidative effect of Cannabis sativa L. extract (CE) on malondialdehyde (MDA) and glutathione (GSH) concentrations as well as on catalase (CAT) activity in BALB/c mice. In total, 40 mice were divided into five equal groups: the aluminum group (7.5 mg AlCl3/kg/d (0.15 LD50), the saline group, the 10% ethanol group (an appropriate amount of the solution for mouse weight), the CE group (1.6 mg CE/g/day), and the aluminum-CE group (7.5 mg AlCl3 plus 1.6 mg CE/g/day). The results of the study showed that CE significantly decreased (by 26.81%, p < 0.05) the concentration of GSH in blood of the mice and the concentration of MDA in the brain (by 82.12%) and liver (by 53.5%) of the mice compared to the respective concentrations in the AlCl3 group. CE significantly (p < 0.05) increased CAT activity in the brain (by 64.79%) and liver (by 72.37%) of the mice after the AlCl3-induced prooxidant effect. The results showed the antioxidant activity of cannabidiolic acid (CBDA) in vitro. The findings in vivo indicate that Cannabis sativa L. is a good source of natural antioxidants and can be used in the management of oxidative stress

The Influence of Different Oregano Species on the Antioxidant Activity Determined Using HPLC Postcolumn DPPH Method and Anticancer Activity of Carvacrol and Rosmarinic Acid

The aim of this study was to evaluate concentration-dependent antioxidant and anticancer activities of CA and RA in ethanol extracts of three different Oregano species (Origanum onites L., Origanum vulgare L., and Origanum vulgare ssp. hirtum). The study revealed the highest RA antioxidant activity in O. vulgare ssp. hirtum (9550±95 mmol/g) and the lowest in O. vulgare L. (2605±52 mmol/g) (p0.05) but they had different activities against MDA-MB231 cell line

Rheumatology International / Musculoskeletal ultrasonography in routine rheumatology practice : data from Central and Eastern European countries

The main aim was to gain structured insight into the use of musculoskeletal ultrasonography (MSUS) in routine rheumatology practices in Central and Eastern European (CEE) countries. In a cross-sectional, observational, international, multicenter survey, a questionnaire was sent to investigational sites in CEE countries. Data on all subsequent routine MSUS examinations, site characteristics, MSUS equipment, and investigators were collected over 6 months or up to 100 examinations per center. A total of 95 physicians at 44 sites in 9 countries provided information on a total of 2810 MSUS examinations. The most frequent diagnoses were rheumatoid arthritis (RA) and spondyloarthritis (34.8 and 14.9 % of cases, respectively). Mean number of joints examined was 6.8. MSUS was most frequently performed for diagnostic purposes (58 %), particularly in patients with undifferentiated arthritis, suspected soft tissue disorders, or osteoarthritis (73.085.3 %). In RA patients, 56.3 % of examinations were conducted to monitor disease activity. Nearly all investigations (99 %) had clinical implications, while the results of 78.6 % of examinations (51.699.0 %) were deemed useful for patient education. This first standardized multicountry survey performed in CEEs provided a structured documentation of the routine MSUS use in participating countries. The majority of MSUS examinations were performed for diagnostic purposes, whereas one-third was conducted to monitor disease activity in RA. A majority of examinations had an impact on clinical decision making and were also found to be useful for patient education.(VLID)346787

Music reviews as part of mass culture

The status of contemporary Czech music reviews (also the Czech cultural criticism) ties in with mass culture and trends of postmodern thinking supports. Subjective journalist genres type reviews and critics look like the relevant expert testing about artistic performance, their real aim is economic profitability and fixing a position in their discourse domain. Mass culture can not offer an alternative to itselfa nd that's the reason, why central dichotomy variation - scheme is applicable not only to its products (music CDs, theatrical performances, a new book at he art), but also on the way, which is about these products further talks . Subjective meta - review has a the specific positron in the mass media