Rheumatoid cachexia is under-recognized in clinical practice. The loss of lean body tissue, which characterizes cachexia, is often compensated for by gain in body fat-so called 'cachectic obesity'-so that 85% or more RA patients have a normal BMI. Severe cachexia with loss of weight leads to increased morbidity and premature mortality but loss of muscle bulk with a normal BMI also associates with poor clinical outcomes. Increasing BMI, even into the obese range, is associated with less joint damage and reduced mortality. Measurement of body composition using DXA and other techniques is feasible but the results must be interpreted with care. Newer techniques such as whole-body MRI will help define with more confidence the mass and distribution of fat and muscle and help elucidate the relationships between body composition and outcomes. Cachexia shows little response to diet alone but progressive resistance training and anti-TNF therapies show promise in tackling this potentially disabling extra-articular feature of RA.
Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. MethodsWe did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. FindingsIn the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo.Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases.
Objective: In rheumatoid arthritis (RA) patients, low levels of physical activity (PA) and high levels of sedentary behavior (SB) may play a role in enhancing cardiovascular risk. We do not know how long-term control of disease activity impacts upon daily PA levels and if treated patients attain PA levels seen in healthy controls. We therefore compared habitual levels of PA and SB between female RA patients with low disease activity achieved by anti-tumor necrosis factor (TNF) therapy, those with active arthritis (aRA) and non-RA controls. Methods: We carried out a cross-sectional comparison of 40 RA patients on anti-TNF therapy for >2 years with DAS28<3.2 (tRA), 32 patients on conventional disease modifying anti-rheumatic drugs with DAS28>3.2 (aRA) and 34 healthy controls (C) with the groups matched for age and body mass index. PA was assessed using the ActiGraph accelerometer to determine step count and time spent in moderate-to-vigorous physical activity (MVPA), light activity and sedentary time. Results: Daily step count was 72% higher in tRA and 40% higher in C in comparison to aRA ( p <0.01). Sedentary time (as a proportion of wear time) was 10% less in tRA than aRA ( p =0.03), while light activity time was 18% higher ( p =0.014). Both RA groups had 40% lower MVPA time than C ( p =0.001). Only half of either RA group fulfilled current WHO guidelines for PA compared with 82% of controls. Conclusion: RA patients who had long-term disease suppression were more physically active with less SB compared to RA patients with active disease. They had similar light PA and SB to controls although lower MVPA. Behavioral change interventions are likely to be needed in order to restore moderate exercise, further reduce SB and to meet guidelines for daily PA.
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