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ID PMID Title PublicationDate abstract
31785183 Family History of Rheumatic, Autoimmune, and Nonautoimmune Diseases and Risk of Rheumatoid 2021 Feb OBJECTIVE: Since comorbidities such as autoimmune diseases may be associated with rheumatoid arthritis (RA) risk, we hypothesized that a family history of these other conditions might also predict RA. Therefore, we aimed to determine the association between family history of 79 comorbidities and RA. METHODS: This case-control study identified 821 cases of RA in the Mayo Clinic Biobank (positive predictive value 95%) and matched 3 controls to each case based on age, sex, recruitment year, and location. Patients self reported family history and characteristics (adjusted). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for RA risk according to the presence of family history for each comorbidity, adjusted for body mass index, race, and smoking. RESULTS: Family history of several conditions was associated with developing RA, including rheumatic autoimmune diseases (OR(adj) 1.89 [95% CI 1.41-2.52]), pulmonary fibrosis (OR(adj) 2.12 [95% CI 1.16-3.80]), inflammatory bowel disease (OR(adj) 1.45 [95% CI 1.05-1.98]), hyper/hypothyroidism (OR(adj) 1.34 [95% CI 1.10-1.63]), and obstructive sleep apnea (OR(adj) 1.28 [95% CI 1.05-1.55]). Parkinson's disease and type 2 diabetes mellitus were associated with a statistically decreased risk of RA that did not reach the prespecified significance threshold of P < 0.01 (OR(adj) 0.70 [95% CI 0.49-0.98] and OR(adj) 0.81 [95% CI 0.67-0.97], respectively). Analyses among 143 cases of incident RA were similar and also suggested an association with a family history of autism (OR 10.5 [95% CI 2.51-71.3]). CONCLUSION: Family history of several autoimmune and nonautoimmune comorbidities was associated with increased risk of RA, providing an opportunity to identify novel populations at risk for RA.
34389605 Fatigue in patients with early rheumatoid arthritis undergoing treat-to-target therapy: pr 2022 Mar OBJECTIVES: Fatigue is a frequent symptom in rheumatoid arthritis (RA) and has high impact on quality of life. We explored associations between disease activity and fatigue in patients with early RA during the initial 24 months of modern treat-to-target therapy and predictors of fatigue after 24 months of follow-up. METHODS: Data were obtained from the treat-to-target, tight control Aiming for Remission in Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasound in a Clinical Tight Control Regime (ARCTIC) trial. Fatigue was measured on a visual analogue scale (VAS) from 0 to 100 mm and defined as clinically relevant if VAS was ≥20 mm. Baseline predictors of fatigue at 24 months were analysed by multivariable logistic regression. RESULTS: 205 patients with fatigue data at baseline and 24 months were included. Median (25th, 75th percentiles) symptom duration was 5.4 months (2.8, 10.4), fatigue VAS 37.0 mm (13.0, 62.0) and mean Disease Activity Score (DAS) 3.4 (SD 1.1) at baseline. Prevalence of fatigue declined from 69% at baseline to 38% at 24 months. Fewer swollen joints (OR 0.92, 95% CI 0.87 to 0.98, p=0.006), lower power Doppler ultrasound score (OR 0.95, 95% CI 0.90 to 0.99, p=0.027) and higher patient global assessment (PGA) (OR 1.03, 95% CI 1.01 to 1.04, p<0.001) increased the risk of clinically relevant fatigue at 24 months. Not achieving remission at 6 months was associated with a higher risk of reporting fatigue at 24 months. CONCLUSIONS: Fatigue in patients with early RA was prevalent at disease onset, with a rapid and sustained reduction during treatment. Low objective disease activity and high PGA at baseline were predictors of clinically relevant fatigue at 24 months.
32801137 Evaluation of Bone Erosions in Rheumatoid Arthritis: The Ultrasound Score for Erosions Ver 2021 Mar OBJECTIVE: To evaluate the relationship between the UltraSound Score for Erosions (USSe) and the modified Sharp/van der Heijde score for erosions (SHSe). METHODS: One hundred eight patients with rheumatoid arthritis (RA) were included. On radiography, SHSe was evaluated by 2 or 3 blinded readers (in case of discordance). On ultrasonography, erosions were scored on 6 bilateral joints (metacarpophalangeal joints 2,3,5; metatarsophalangeal joints 2,3,5) with a 4-point scale to calculate the USSe. RESULTS: The Pearson correlation was good (r = 0.68, P < 0.001) and the agreement illustrated by a Bland-Altman plot was excellent (91%) between the 2 scores, which were complementary in detecting erosions. CONCLUSION: The USSe seems to be a valuable tool for assessing erosive damage in RA.
33953418 Bone Histomorphometry of Femoral Head Cancellous Bone in Patients Who Underwent Total Hip 2021 Apr Rheumatoid arthritis (RA) affects the hip joints. The microarchitecture of the cancellous bone in RA-affected hip joints has been unclear. Here we investigated the bone metabolism changes in the subcapital cancellous bone of destructive hips of RA patients (n=26 patients; 28 hip joints) which were classified by Larsen grade on X-ray into the groups: destructive hip (Des) (Larsen grade IV, n=18) and neck fracture (Fx) (Larsen grade 0 or 1, n=10). The femoral heads of the Des-group showed significantly higher trabecular thickness versus those of the Fx-group (179±30.8 vs. 151±23.5 μm, p=0.02). The Des-group had significantly higher osteoid volume/tissue volume (OV/TV) and osteoid volume/bone volume (OV/BV) ratios than the Fx-group (OV/TV: 0.72±0.70% vs. 0.27±0.32%, p=0.028; OV/BV: 2.96±2.85% vs. 1.24±1.31%, p=0.039). The osteoblast and osteoclast surface areas of the Des-group were remarkably higher than those of the Fx-group (9.80±10.9 vs. 0.15±0.15%, p=0.0005; 0.34±0.48 vs. 0.06±0.06%, p=0.0285, respectively). The T-scores of hip (femoral neck) bone mineral density (BMD) of the Fx-group were significantly lower versus those of the Des-group (-3.1±0.76 vs. -1.6±1.17, p<0.01). Increased osteoid and resorption parameters and higher femoral neck BMD demonstrate a high bone-turnover state in response to destructive changes in the hips of RA patients.
34526250 Evaluation of mandibular condyle trabecular structure in patients with rheumatoid arthriti 2022 Feb OBJECTIVES: The aim of this study was to compare the fractal dimension (FD) of trabecular structure of the mandibular condyles in patients with rheumatoid arthritis (RA) to patients without RA. Correlations between condylar FD and bone mineral density T-scores in the femoral neck and lumbar spine were also examined. STUDY DESIGN: The RA study group patients were divided into 3 categories (33 normal, 33 osteopenic, and 34 osteoporotic) according to T-scores. The control group without RA was sex- and age-matched with the study group. FD was calculated from panoramic radiographs and compared between the study and control groups. The relationships between FD values and femoral neck and L1-L4 lumbar spine T-scores were investigated for study and control groups. Significance was established at P < .05. RESULTS: The mean FD values of the entire study group and of each category in the study group were significantly lower than those of the control group (P < .001). There were no significant differences in FD values among the 3 RA categories (P > .05). No significant correlations appeared between FD and femoral neck or lumbar spine T-scores (P ≥ .063). CONCLUSIONS: Fractal analysis of the condyles on panoramic radiographs can distinguish RA from healthy condyles, even if the patients with RA have normal bone mineral density T-scores.
33827708 Osteoporotic fractures in rheumatoid arthritis patients in Argentina: a matched retrospect 2021 Apr 7 BACKGROUND: To compare the incidence of osteoporotic fractures in patients with rheumatoid arthritis (RA) with matched controls from a university hospital. METHODS: Consecutive RA patients (n = 100) were matched (age and sex) with controls (1:2). The follow-up period began at the index date, defined as the date of diagnosis for RA patients and the date of the first medical claim at the Health Management Organization (HMO) for non-RA patients. Fracture incidence rates per 1000 persons-years (PY) for distinct types of fractures were calculated. Multivariate cox regression analysis was performed to identify factors associated with fractures. RESULTS: One hundred RA patients were followed for a total of 975.1 patients-years and 200 controls for 1485.7 patients-years. No difference was found in the overall fracture incidence rate per 1000 PY between RA and controls (19.5, 95% CI 12.7-28.6 vs 12.1, 95% CI 7.7-18.7, p = 0.07). In the Cox regression analysis, only age (HR 1.06, 95% CI 1.02-1.11, p = 0.006) and history of a prior fracture (HR 9.85, 95% CI 2.97-32.64, p <  0.001) were associated with fractures after the index date. The stratified analysis of the fractures by location showed that only the vertebral fractures were more frequent in RA patients compared with controls (12.9 per 1000 PY, 95% CI 8.9-25.8, vs. 3.4, 95% CI 1.4-8.1, respectively, p = 0.01). CONCLUSION: Patients with RA didn't show an overall increased risk of osteoporotic fractures compared with matched controls, but vertebral fractures were more frequently observed in patients with RA.
35003113 LncRNA Expression Profiles in Systemic Lupus Erythematosus and Rheumatoid Arthritis: Emerg 2021 Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are two common multisystem autoimmune diseases that share, among others, many clinical manifestations and serological features. The role of long non-coding RNAs (lncRNAs) has been of particular interest in the pathogenesis of autoimmune diseases. Here, we aimed to summarize the roles of lncRNAs as emerging novel biomarkers and therapeutic targets in SLE and RA. We conducted a narrative review summarizing original articles on lncRNAs associated with SLE and RA, published until November 1, 2021. Based on the studies on lncRNA expression profiles in samples (including PBMCs, serum, and exosomes), it was noted that most of the current research is focused on investigating the regulatory mechanisms of these lncRNAs in SLE and/or RA. Several lncRNAs have been hypothesized to play key roles in these diseases. In SLE, lncRNAs such as GAS5, NEAT1, TUG1, linc0949, and linc0597 are dysregulated and may serve as emerging novel biomarkers and therapeutic targets. In RA, many validated lncRNAs, such as HOTAIR, GAS5, and HIX003209, have been identified as promising novel biomarkers for both diagnosis and treatment. The shared lncRNAs, for example, GAS5, may participate in SLE pathogenesis through the mitogen-activated protein kinase pathway and trigger the AMP-activated protein kinase pathway in RA. Here, we summarize the data on key lncRNAs that may drive the pathogenesis of SLE and RA and could potentially serve as emerging novel biomarkers and therapeutic targets in the coming future.
34248970 Circulating and Synovial Pentraxin-3 (PTX3) Expression Levels Correlate With Rheumatoid Ar 2021 AIMS: To determine the relationship between PTX3 systemic and synovial levels and the clinical features of rheumatoid arthritis (RA) in a cohort of early, treatment naïve patients and to explore the relevance of PTX3 expression in predicting response to conventional-synthetic (cs) Disease-Modifying-Anti-Rheumatic-Drugs (DMARDs) treatment. METHODS: PTX3 expression was analyzed in 119 baseline serum samples from early naïve RA patients, 95 paired samples obtained 6-months following the initiation of cs-DMARDs treatment and 43 healthy donors. RNA-sequencing analysis and immunohistochemistry for PTX3 were performed on a subpopulation of 79 and 58 synovial samples, respectively, to assess PTX3 gene and protein expression. Immunofluorescence staining was performed to characterize PTX3 expressing cells within the synovium. RESULTS: Circulating levels of PTX3 were significantly higher in early RA compared to healthy donors and correlated with disease activity at baseline and with the degree of structural damages at 12-months. Six-months after commencing cs-DMARDs, a high level of PTX3, proportional to the baseline value, was still detectable in the serum of patients, regardless of their response status. RNA-seq analysis confirmed that synovial transcript levels of PTX3 correlated with disease activity and the presence of mediators of inflammation, tissue remodeling and bone destruction at baseline. PTX3 expression in the synovium was strongly linked to the degree of immune cell infiltration, the presence of ectopic lymphoid structures and seropositivity for autoantibodies. Accordingly, PTX3 was found to be expressed by numerous synovial cell types such as plasma cells, fibroblasts, vascular and lymphatic endothelial cells, macrophages, and neutrophils. The percentage of PTX3-positive synovial cells, although significantly reduced at 6-months post-treatment as a result of global decreased cellularity, was similar in cs-DMARDs responders and non-responders. CONCLUSION: This study demonstrates that, early in the disease and prior to treatment modification, the level of circulating PTX3 is a reliable marker of RA activity and predicts a high degree of structural damages at 12-months. In the joint, PTX3 associates with immune cell infiltration and the presence of ectopic lymphoid structures. High synovial and peripheral blood levels of PTX3 are associated with chronic inflammation characteristic of RA. Additional studies to determine the mechanistic link are required.
34380392 Efficacy of Intra-Articular Injection of 10 mg and 20 mg Triamcinolone for Rheumatoid Arth 2021 Sep Background: To compare the efficacy of intra-articular injection (IA) with 10 mg and 20 mg triamcinolone for treatment of rheumatoid arthritis (RA) of the wrist joint. Methods: We enrolled 20 patients with swelling and pain in wrist due to RA in the present prospective, randomized, pilot study. Patients were randomly assigned in a 1:1 ratio to either the 20 mg or 10 mg group, and received IA of the appropriate dose of triamcinolone. Efficacy was assessed by recording Numerical Rating Scale (NRS) for pain and improvement in power doppler (PD) scale score at weeks 1, 4, and 12 of treatment compared with baseline. The shortened Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) was recorded at baseline and week 12. Results: The NRS was found to be significantly improved at weeks 4 (p = 0.006) and 12 (p = 0.036) among the total study population. Neither the change in NRS nor the improvement PD scale score from baseline were significantly different between the two groups at any week (NRS: week 1, p = 0.617; week 4, p = 0.727; and week 12, p = 0.878; PD scale score: week 1, p = 0.370; week 4, p = 1.000; and week 12, p = 0.179). Among the entire study population, the QuickDASH was not significantly improved at week 12 nor was the change from baseline significantly different between the two groups at week 12 (p = 0.592). Conclusions: IA of triamcinolone was effective for pain relief in context of RA in the wrist joint. However, in terms of NRS, improvement of PD scale score, and QuickDASH score, the efficacies of 10 mg and 20 mg triamcinolone were not significantly different. Thus, IA of 10 mg triamcinolone may be sufficient for the treatment of RA in the wrist joint.
33781451 Anti-rheumatoid arthritis potential of diterpenoid fraction derived from Rhododendron moll 2021 Mar Rhododendron molle G. Don is first recorded in Shengnong's Herbal Classic, and its fruits, which are termed as Liuzhouzi, are often used to treat rheumatoid arthritis in Chinese folk. During our ongoing investigation to develop a safer and potential new arthritis therapy, a process for the preparation of diterpenoid fraction from Rhododendron mollefruits was established. In order to evaluate the main components and the anti-rheumatoid arthritis effect of the diterpenoid fraction, phytochemical and pharmacological experiments were used. As the result, the main components of diterpenoid fraction were identified as rhodojaponin III (1), rhodojaponin VI (2), 2-O-methylrhodojaponin (3), and 5'-β-D-glucopyranosy-loxyjasmonic acid (4). These four components constitute greater than 95% of diterpenoid fraction using area normalization method of HPLC-ELSD. The results of CIA rat experiment showed that high dose of diterpenoid fraction (0.6 mg·kg(-1)·d(-1)) significantly alleviated the symptoms of rheumatoid arthritis, similar to tripterygium polyglycosides, an effective RA therapy. Preliminary mechanism studies indicated that diterpenoid fraction significantly inhibited the abnormal proliferation of T and B lymphocytes, and remarkably reduced the levels of pro-inflammatory cytokines IL-6, IL-1β and TNF-α. Overall, our findings may provide a more effective and safe alternative treatment for RA using common clinical Chinese medicines like tripterygium polyglycosides.
33131220 Developing the Korean Educational Needs Assessment Tool (Korean ENAT) in rheumatoid arthri 2021 Jul BACKGROUND/AIMS: This study was performed to undertake cross-cultural adaptation and validation of the Educational Needs Assessment Tool (ENAT) in rheumatoid arthritis (RA) for use in Korea. METHODS: The study involved two main phases: cross-cultural adaptation of the ENAT from English into Korean, and validation of the Korean ENAT. The first phase followed the established process of cross-cultural adaptation of self-report measures, and in the second phase, the Korean ENAT data were analyzed using the Rasch measurement model. Fit to the model was determined using the observed data infit and outfit statistics. Additional tests of validity included unidimensionality and internal consistency. RESULTS: Adequate conceptual equivalence was achieved following the adaptation process. A total of 123 patients completed the Korean ENAT. The mean age was 46.7 ± 12.3 years and the majority of patients (81.3%) were female. Thirty-five of the 39 items gave good fit to the model. The four items deviating from the model had infit and outfit > 1.50. The item separation index (5.26) and item reliability index (0.97) provided evidence for good reliability of items. All seven domains of the Korean ENAT fit the Rasch model. The internal consistency of the Korean ENAT was high, and unidimensionality was confirmed (person separation index, 3.41; reliability index, 0.92; item separation index, 16.82; reliability index, 1.00). CONCLUSION: Using the standard procedure for cross-cultural adaptation, the ENAT has been adapted into Korean, and Rasch analysis has confirmed the construct validity, reliability, and unidimensionality of the Korean ENAT.
34680168 Changes of Metabolic Biomarker Levels upon One-Year Anti-TNF-α Therapy in Rheumatoid Arth 2021 Oct 18 BACKGROUND: Cardiovascular (CV) morbidity, mortality, and metabolic syndrome are associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Here, lipids and other metabolic markers in relation to vascular function and clinical markers were evaluated in RA and AS patients undergoing one-year anti-TNF therapy. PATIENTS AND METHODS: Fifty-three patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Various lipids, paraoxonase (PON) and arylesterase (ARE) activities, myeloperoxidase (MPO) and adipokine levels were determined overtime. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. RESULTS: Anti-TNF therapy decreased ARE activity, MPO, adiponectin, and chemerin levels after 12 months (p < 0.05). Lipids, PON activity, and leptin remained unchanged. Regression analyses suggested variable associations of IMT, PWV, and FMD with ARE, MPO, leptin, and lipids (p < 0.05). On the other hand, these metabolic parameters were significantly associated with disease duration, CV history, CRP, obesity, PWV, and IMT (p < 0.05). One-year anti-TNF treatment together with baseline leptin (p = 0.039) or CRP (p = 0.016) levels determined 12 months of lipid changes overtime. TNF inhibition together with baseline disease activity determined ARE activity changes (p = 0.046). Anti-TNF therapy and baseline chemerin levels determined IMT changes overtime (p = 0.003). CONCLUSIONS: Assessment of various metabolic parameters together with disease activity, CRP, and ultrasound-based techniques may exert additional value in determining CV burden and in monitoring the effects of biologics on preclinical vascular pathophysiology.
34487094 Rheumatoid Arthritis disease activity assessment in routine care: performance of the most 2021 Sep 2 BACKGROUND AND AIM: To evaluate the convergent and discriminative validity of many continuous composite disease activity indices and patient-reported outcome measures (PROMs) in rheumatoid arthritis (RA). METHODS: In consecutive RA patients in moderate or high disease activity, according to the Simplified Disease Activity Index (SDAI) definition, were computed four additional composite disease activity indices, the 28-joint Disease Activity Score - erythrocyte sedimentation rate (DAS28-ESR), the Clinical Disease Activity Index (CDAI), the Chronic Arthritis Systemic Index (CASI), and the Mean Overall Index for RA (MOI-RA), and five PROMs, the Patients' Activity Scale (PAS), the Rheumatoid Arthritis Impact of Disease (RAID), the 5-item RA Disease Activity Index (RADAI-5), the Routine Assessment of Patient Index Data (RAPID3), and the Clinical Arthritis Activity (PRO-CLARA). Spearman's rho correlation coefficients were determined to assess their convergent validity, and discriminative performance was calculated by the area under the receiver-operating curve (AUC-ROC). The patients' opinion of their symptomatic status (PASS) was used as the external criterion. RESULTS: 246 RA patients with moderate (29.3%) or high disease activity (70.7%) have been assessed. The indices all showed a significant correlation (p <0.0001 for all). Among the composite disease activity indices, the CDAI was the one that showed the best discriminating ability compared to the PASS (AUC = 0.962), while among the PROMs the RAID was the most performing (AUC = 0.879). CONCLUSIONS: CDAI as composite index of disease activity, and RAID as PROM, are the two instruments with the best performances in relation to PASS. The use of validated disease activity measures can help in clinical practice to adopt treat-to-target strategies in RA patients. (www.actabiomedica.it).
33837917 Tofacitinib in the Treatment of Moderate-to-Severe Rheumatoid Arthritis in China: A Cost-E 2021 May INTRODUCTION: To estimate the cost-effectiveness of tofacitinib for patients with moderate-to-severe rheumatoid arthritis (RA) who failed conventional synthetic disease-modifying antirheumatic drugs from the Chinese healthcare system perspective. METHODS: An individual patient simulation model was used to estimate the lifetime cost and effectiveness. The comparator sequence commenced with etanercept, followed by rituximab-tocilizumab- non-biologic therapy. The intervention sequences were assumed to add tofacitinib to different positions in the comparator sequence. Quality-of-life estimates were generated by mapping Health Assessment Questionnaire scores to utility with the algorithm derived from a Chinese population. Scenario analyses, univariable and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. RESULTS: Compared with the comparator sequence, patients receiving tofacitinib as the first-, second-, third- and fourth-line treatment gained additional 0.49, 0.59, 0.44 and 0.53 QALYs, respectively, and the use of tofacitinib as the first- and second-line treatment was less costly, whereas the use of tofacitinib as the third- and fourth-line treatment cost an additional $234,998 and $381,116, respectively. This produced an incremental cost-effectiveness ratio of $333.73 and $9669.34/QALY, respectively. CONCLUSION: Tofacitinib is estimated to be dominant in both the first- and second-line settings and to be highly cost-effective in both the third- and fourth-line settings.
33376015 Peripheral Volumetric Muscle Area and Total Body Volume in Postmenopausal Women With Rheum 2021 Oct The effect of rheumatoid arthritis (RA) on peripheral muscle parameters is not completely understood. This study aimed to elucidate the influence of RA on peripheral muscle area and whole body skeletal muscle mass index (SMI) using peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in postmenopausal women. This cross-sectional study included 54 postmenopausal women with RA and 86 healthy controls. Peripheral quantitative computed tomography and dual-energy X-ray absorptiometry were used to measure the muscle cross-sectional area and skeletal muscle mass. Muscle strength was assessed using a handheld dynamometer. Additionally, the effects of RA on muscle area and density as well as the bone / muscle area ratio were analyzed using multivariate models. The muscle area index of the thigh and forearm were correlated between both groups (RA: r = 0.357, p = 0.030; and healthy controls: r = 0.608, p < 0.001) and each index correlated with SMI in RA and healthy controls (p < 0.001). Bone / muscle area ratio correlated between forearms and thighs in health controls only (r = 0.547, p < 0.001). The RA group had a decreased thigh muscle area (p = 0.014); the fat area and fat muscle area ratio at the thigh and forearm were significantly increased (all p < 0.001), as well as thigh bone / muscle area ratio (p = 0.015). The RA group also had significantly lower forearm muscle density (p < 0.001). A sensitivity analysis excluding those on bisphosphonates led to similar results. Independent of RA, the thigh and forearm muscle area correlate with each other and with SMI. Differences in the bone / muscle ratio between RA and healthy controls may indicate regional muscle effects of inflammation and inactivity.
34215316 Effectiveness of bazedoxifene in preventing glucocorticoid-induced bone loss in rheumatoid 2021 Jul 2 OBJECTIVE: To evaluate the effectiveness of bazedoxifene in preventing bone loss in patients with rheumatoid arthritis (RA) receiving low-dose glucocorticoids (GCs). METHODS: In this randomized, controlled, open-label study, we assigned postmenopausal women with osteopenia who had been receiving low-dose GCs for RA to two groups: a group receiving bazedoxifene (20 mg/day) with elemental calcium 1200 mg and vitamin D 800 IU daily (bazedoxifene group) and a group receiving the same doses of calcium and vitamin D only (control group). As primary outcome, bone mineral density (BMD) change in the lumbar spine (L-spine) from baseline to 48 weeks was assessed. Changes in BMD in the femur, trabecular bone score, bone turnover markers, and development of fracture were assessed as secondary outcomes. For intention-to-treat analysis, 20 completed data sets were created by applying multiple imputations by chained equations. RESULTS: A total of 114 patients (57 patients in each group) were recruited. A significant increase in L-spine BMD (0.015 g/cm(2), P = 0.007) was observed in the bazedoxifene group, and the increase was significantly higher than in the control group (0.013, 95% CI 0.0003-0.026, P = 0.047). Reductions in bone turnover markers in the bazedoxifene group were significantly greater than in the control group. Only one fracture was observed in the bazedoxifene group, while four fractures developed in the control group. CONCLUSION: In postmenopausal patients with RA receiving low-dose GCs, bazedoxifene improved BMD and reduced bone turnover markers. However, the change in BMD did not exceed the least significant change. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02602704 .
34618210 [Data analysis in rheumatology practices : Possibilities, limitations, and results]. 2021 Nov Data analyses in rheumatology practices can be used as a feedback system in quality management. Implementation of a representative patient survey enables evaluation of one's own work and can be used for external presentation of the practice. Patient education and the structured use of specialist rheumatology assistants were evaluated by means of a survey. Systematic screening for depressive symptoms was carried out and enables a better understanding of patients and their "unmet needs". An analysis of the diseases and the patients in terms of physical function, disease activity, medication, and concomitant diseases is possible using structured patient documentation in a specialized documentation system. Within the RHADAR network (RheumaDatenRhePort G.b.R.), the proportion of rheumatoid arthritis patients treated with Janus kinase inhibitors was compared between different centers. Patients suitable for clinical trials can be filtered out of a structured documentation system.
32502346 Nanomedicine for the Treatment of Rheumatoid Arthritis. 2021 Feb 1 Rheumatoid arthritis (RA) is a chronic autoimmune disease that results in severe inflammatory microenvironments in the joint tissues. In clinics, disease-modifying antirheumatic drugs (DMARDs) are generally prescribed to patients with RA, but their long-term use often shows toxicity in some organs such as the gastrointestinal system, skin, and kidneys and immunosuppression-mediated infection. Nanomedicine has emerged as a new therapeutic strategy to efficiently localize the drugs in inflamed joints for the treatment of RA. In this Review, we introduce recent research in the area of nanomedicine for the treatment of RA and discuss how the nanomedicine can be used to deliver therapeutic agents to the inflamed joints and manage the progression of RA, particularly focusing on targeted delivery, controlled drug release, and immune modulation.
35008858 New Proteins Contributing to Immune Cell Infiltration and Pannus Formation of Synovial Mem 2021 Dec 31 An inflamed synovial membrane plays a major role in joint destruction and is characterized by immune cells infiltration and fibroblast proliferation. This proteomic study considers the inflammatory process at the molecular level by analyzing synovial biopsies presenting a histological inflammatory continuum throughout different arthritis joint diseases. Knee synovial biopsies were obtained from osteoarthritis (OA; n = 9), chronic pyrophosphate arthropathy (CPPA; n = 7) or rheumatoid arthritis (RA; n = 8) patients. The histological inflammatory score was determined using a semi-quantitative scale based on synovial hyperplasia, lymphocytes, plasmocytes, neutrophils and macrophages infiltration. Proteomic analysis was performed by liquid chromatography-mass spectrometry (LC-MS/MS). Differentially expressed proteins were confirmed by immunohistochemistry. Out of the 1871 proteins identified and quantified by LC-MS/MS, 10 proteins (LAP3, MANF, LCP1, CTSZ, PTPRC, DNAJB11, EML4, SCARA5, EIF3K, C1orf123) were differentially expressed in the synovial membrane of at least one of the three disease groups (RA, OA and CPPA). Significant increased expression of the seven first proteins was detected in RA and correlated to the histological inflammatory score. Proteomics is therefore a powerful tool that provides a molecular pattern to the classical histology usually applied for synovitis characterization. Except for LCP1, CTSZ and PTPRC, all proteins have never been described in human synovitis.
33068028 Population pharmacokinetic analysis of peficitinib in patients with rheumatoid arthritis. 2021 Apr AIMS: To analyse the population pharmacokinetics (PK) of peficitinib in patients with rheumatoid arthritis (RA) and assess the potential PK covariates to identify the requirement for dose adjustment in RA patients. METHODS: The analysis incorporated 2464 observations from 98 healthy volunteers and 4919 observations from 989 RA patients. A population PK model for peficitinib in RA patients was constructed by a nonlinear mixed effect model using NONMEM with prior information from a healthy volunteer model. RESULTS: A 2-compartment model with sequential zero- and first-order absorption and lag time was constructed for RA patients. Covariate exploration in the RA patient model revealed that estimated glomerular filtration rate (eGFR) and lymphocyte count had a significant effect on apparent total systemic clearance (CL), which was 91.7 L/h (2.3% relative standard error). Compared with the mean population CL, the model predicted mean changes in CL of 12.3 and -10.7% in patients with observed minimum and maximum lymphocyte count of 500 and 4600 10(6) /L, respectively, and mean changes in CL of -17.8 and 16.7% in patients with minimum and maximum eGFR of 36.4 and 188 mL/min/1.73m(2) , respectively. The simulated population mean area under plasma concentration-time curve for 24 hours after dosing showed a 1.35-fold increase in patients with severe renal impairment (eGFR 22.5 mL/min/1.73m(2) ) compared with patients with reference eGFR (91.5 mL/min/1.73m(2) ). CONCLUSION: The population PK model identified eGFR and lymphocyte count as covariates for CL. The magnitude of changes was not considered clinically relevant, indicating no requirement for dose adjustment.