Objective. Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease-related variables in patients with RA from 21 countries. patients from 58 sites in 21 countries were enrolled in QUEST-RA: 79% were women, >90% were white, mean age was 57 years, and mean disease duration was 11.6 years. Only 13.8% of all patients reported physical exercise >3 times weekly. The majority of the patients were physically inactive with no regular weekly exercise: >80% in 7 countries, 60 -80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. Conclusion. In many countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels.
Objective:To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country.Methods:The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST–RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 “high GDP” countries with GDP per capita greater than US$24 000 and 11 “low GDP” countries with GDP per capita less than US$11 000.Results:Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = −0.78, 95% CI −0.56 to −0.90, r2 = 61%). Disease activity levels differed substantially between “high GDP” and “low GDP” countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents.Conclusions:The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in “low GDP” than in “high GDP” countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.
The most important feature of B cells is the production of Abs upon activation; additionally, B cells produce pro- and anti-inflammatory cytokines in response to certain stimuli. IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) that suppress autoimmune and inflammatory responses. B cells play a crucial role in the development and maintenance of the chronic inflammatory autoimmune disease rheumatoid arthritis (RA); however, controversial data are available on IL-10- producing Bregs in RA. Our aim was to identify the optimal conditions that induce IL-10 Bregs and, furthermore, to shed light on the signaling pathways that are responsible for their expansion. The results show that dual stimulation by CpG and CD40L for 48 h is optimal for IL-10 induction, and this can be synergistically boosted by IL-21. We identified the CD19CD27 memory B cell population as the major source of IL-10 Bregs. We detected significantly fewer CD19CD27IL-10 cells in RA patients compared with healthy controls, and these were functionally defective in suppressing IFN-γ production by CD4 T cells in coculture. IL-21 drastically increased the number of IL-10 Bregs within the CD19CD27 and CD19CD27 populations; furthermore, it induced the appearance of IL-10Blimp-1 plasmablasts. Monitoring the phosphorylation of key signaling molecules revealed that activation of ERK, p38, and CREB is indispensable for the induction of IL-10 production, whereas phosphorylation of STAT3 further enhances IL-10 expression in human Bregs. We conclude that CREB and STAT3 are the key transcription factors responsible for the expansion and differentiation of human IL-10-producing Bregs.
Objective. To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to >1 disease-modifying antirheumatic drug.Methods. This combined phase I/II study investigated the safety and efficacy of 3 doses of ofatumumab. In part A (phase I), 39 patients received 2 intravenous (IV) infusions of ofatumumab (300 mg, 700 mg, or 1,000 mg) or placebo in a 4:1 ratio 2 weeks apart, using a specified premedication and infusion regimen. In part B (phase II), 225 patients received study treatment as per phase I in a 1:1:1:1 ratio. Safety was assessed by adverse events (AEs) and laboratory parameters. Efficacy was assessed by the American College of Rheumatology 20% criteria for improvement (ACR20), the Disease Activity Score in 28 joints, and the European League Against Rheumatism (EULAR) response criteria. B cell pharmacodynamics were also investigated.Results. AEs were predominantly reported at the first infusion and were mostly mild to moderate in intensity. Rapid and sustained peripheral B cell depletion was observed in all dose groups. In phase II, patients in all ofatumumab dose groups had significantly higher ACR20 response rates (40%, 49%, and 44% for the 300 mg, 700 mg, and 1,000 mg doses, respectively) than did patients receiving placebo (11%) at week 24 (P < 0.001). Overall, 70% of patients receiving ofatumumab had a moderate or good response according to the EULAR criteria at week 24.Conclusion. Our findings indicate that ofatumumab, administered as 2 IV infusions of doses up to 1,000 mg, is clinically effective in patients with active RA.Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease characterized by symmetric inflammation of synovial joints, leading to progressive ClinicalTrials.gov identifier: NCT00291928.
Background Patients’ needs and perspectives are important determinants of treatment success in rheumatoid arthritis (RA). Assessing patients’ perspectives can help identify unmet needs and enhance the understanding of treatment benefits. Objective The SENSE study assessed the impact of inadequate response to disease-modifying antirheumatic drugs (DMARDs) on treatment satisfaction, disease outcomes, and patient perspectives related to RA disease management. Methods SENSE was a noninterventional, cross-sectional study conducted in 18 countries across Europe, Asia, and South America. Adult patients with poorly controlled RA of moderate/high disease activity were eligible. Patient satisfaction was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM v1.4). Treatment adherence, healthcare resource utilization (HRU), quality of life (QoL), work ability, digital health literacy (DHL), patient preference information, and treatment strategy were also assessed. Results A total of 1624 patients were included in the study: most were female (84.2%) and middle-aged, and mean disease duration was 10.5 years. Mean TSQM global satisfaction subscore was 60.9, with only 13.5% of patients reporting good treatment satisfaction (TSQM global ≥80). The strongest predictor of good treatment satisfaction was treatment with advanced therapies. Most patients (87.4%) reported good treatment adherence. In general, patients had impaired QoL and work ability, high HRU, and 67.4% had poor DHL. Leading treatment expectations were “general improvement of arthritis” and “less joint pain”. Most patients preferred oral RA medications (60.7%) and rapid (≤1 week) onset of action (71.1%). “Increased risk for malignancies” and “increased risk for cardiovascular disease” were the least acceptable side effects. Despite suboptimal control, advanced therapies were only used in a minority of patients, and DMARD switches were planned for only half of the patients. Conclusion Suboptimal disease control negatively impacts treatment satisfaction, work ability, QoL, and HRU. Data collected on patient perspectives may inform shared decision-making and optimize treat-to-target strategies for improving patient outcomes in RA.
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