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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
33513531 Juvenile idiopathic arthritis, gait characteristics and relation to function. 2021 Mar BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is a chronic inflammatory arthritis that impacts biomechanical features of gait. This systematic review describes the effects of JIA on gait motion parameters and walking performance. METHODS: Six databases were searched (PubMed/Medline, Cochrane, the EBSCOHost database SPORTDiscus, Web of Science, and Embase). Studies were restricted to children with any subtype of JIA who were assessed for gait motion features (kinematic, kinetic, temporalspatial) or walking performance (velocity or distance covered); could include intervention or treatment exposure with measures of gait and gait speed; could involve comparison of gait in JIA to healthy controls. Quality of evidence was assessed using the GRADE system. This systematic review was registered at PROSPERO (CRD42018109582) RESULTS: The search yielded 625 papers, 23 of which described biomechanical features of gait and/or assessed walking performance. Twenty studies measured walking velocity and walking ability using simple field tests or laboratory methods. Eleven studies measured temporalspatial parameters such as cadence, step length, stride length, step width, single and double support time. Nine studies evaluated kinetic measurements including joint power, flexion and extension and joint moments. Nine studies evaluated kinematic parameters including range of motion, pelvic tilt, center of motion and trunk sway. CONCLUSIONS: Key features of gait in children with JIA include slower gait velocity, shortened step length, decreased range of motion at the hip, knee and ankle with trend towards flexion, decreased joint power, anteriorly tilted pelvis and trunk with shifted center of motion. There is a potential to ameliorate JIA-related gait changes with exercise and/or pharmaceutical interventions.
34220796 Driving β(2)- While Suppressing α-Adrenergic Receptor Activity Suppresses Joint Patholog 2021 OBJECTIVE: Hypersympathetic activity is prominent in rheumatoid arthritis, and major life stressors precede onset in ~80% of patients. These findings and others support a link between stress, the sympathetic nervous system and disease onset and progression. Here, we extend previous research by evaluating how selective peripherally acting α/β(2)-adrenergic drugs affect joint destruction in adjuvant-induced arthritis. METHODS: Complete Freund's adjuvant induced inflammatory arthritis in male Lewis rats. Controls received no treatment. Arthritic rats then received vehicle or twice-daily treatment with the α-adrenergic antagonist, phentolamine (0.5 mg/day) and the β(2)-adrenergic agonist, terbutaline (1200 µg/day, collectively named SH1293) from day (D) of disease onset (D12) through acute (D21) and severe disease (D28). Disease progression was assessed in the hind limbs using dorsoplantar widths, X-ray analysis, micro-computed tomography, and routine histology on D14, D21, and D28 post-immunization. RESULTS: On D21, SH1293 significantly attenuated arthritis in the hind limbs, based on reduced lymphocytic infiltration, preservation of cartilage, and bone volume. Pannus formation and sympathetic nerve loss were not affected by SH1293. Bone area and osteoclast number revealed high- and low-treatment-responding groups. In high-responding rats, treatment with SH1293 significantly preserved bone area and decreased osteoclast number, data that correlated with drug-mediated joint preservation. SH1293 suppressed abnormal bone formation based on reduced production of osteophytes. On D28, the arthritic sparing effects of SH1293 on lymphocytic infiltration, cartilage and bone sparing were maintained at the expense of bone marrow adipocity. However, sympathetic nerves were retracted from the talocrural joint. CONCLUSION AND SIGNIFICANCE: Our findings support a significant delay in early arthritis progression by treatment with SH1293. Targeting sympathetic neurotransmission may provide a strategy to slow disease progression.
34162435 Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA): protocol for a prospective obser 2021 Jun 24 BACKGROUND: Pain and fatigue are persistent problems in people with rheumatoid arthritis. Central sensitisation (CS) may contribute to pain and fatigue, even when treatment has controlled inflammatory disease. This study aims to validate a self-report 8-item questionnaire, the Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) questionnaire, developed to measure central pain mechanisms in RA, and to predict patient outcomes and response to treatment. A secondary objective is to explore mechanisms linking CS, pain and fatigue in people with RA. METHODS/DESIGN: This is a prospective observational cohort study recruiting 250 adults with active RA in secondary care. The CAP-RA questionnaire, demographic data, medical history, and patient reported outcome measures (PROMs) of traits associated with central sensitization will be collected using validated questionnaires. Quantitative sensory testing modalities of pressure pain detection thresholds, temporal summation and conditioned pain modulation will be indices of central sensitization, and blood markers, swollen joints and ultrasound scans will be indices of inflammation. Primary data collection will be at baseline and 12 weeks. The test-retest reliability of CAP-RA questionnaire will be determined 1 week after the baseline visit. Pain and fatigue data will be collected weekly via text messages for 12 weeks. CAP-RA psychometric properties, and predictive validity for outcomes at 3 months will be evaluated. DISCUSSION: This study will validate a simple self-report questionnaire against psychophysical indices of central sensitization and patient reported outcome measures of traits associated with CS in a population of individuals with active RA. The application of this instrument in the clinical environment could provide a mechanism-based stratification tool to facilitate the provision of targeted therapy to individuals with pain and fatigue in RA, alongside treatments that target joint inflammation. TRIAL REGISTRATION: Clinicaltrials.gov NCT04515589 . Date of registration 17 August 2020.
33090496 Revisiting B cell tolerance and autoantibodies in seropositive and seronegative autoimmune 2021 Feb Autoimmune rheumatic diseases (AIRD) are categorized seropositive or seronegative, dependent upon the presence or absence of specific autoreactive antibodies, including rheumatoid factor and anti-citrullinated protein antibodies. Autoantibody-based diagnostics have proved helpful in patient care, not only for diagnosis but also for monitoring of disease activity and prediction of therapy responsiveness. Recent work demonstrates that AIRD patients develop autoantibodies beyond those contained in the original categorization. In this study we discuss key mechanisms that underlie autoantibody development in AIRD: defects in early B cell development, genetic variants involved in regulating B cell and T cell tolerance, environmental triggers and antigen modification. We describe how autoantibodies can directly contribute to AIRD pathogenesis through innate and adaptive immune mechanisms, eventually culminating in systemic inflammation and localized tissue damage. We conclude by discussing recent insights that suggest distinct AIRD have incorrectly been denominated seronegative.
33780509 Correction to Expression of Concern on: Functional Improvement of Regulatory T Cells from 2021 [This corrects the article DOI: 10.1371/journal.pone.0247971.].
34349504 Erratum: Benefits of Switch from Oral to Subcutaneous Route on Adherence to Methotrexate i 2021 [This corrects the article DOI: 10.2147/PPA.S301010.].
35079183 Anxiety and depression are common in rheumatoid arthritis and correlate with poor quality 2021 OBJECTIVES: We planned this study to assess the prevalence of anxiety and depression in rheumatoid arthritis (RA) patients and its correlation with quality of life (QOL) in these patients. MATERIAL AND METHODS: Eighty-eight patients (76 females) were included in this cross-sectional study. The Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depression. Quality of life was measured using the World Health Organization WHOQOL-BREF. The severity of pain was measured by 100-millimetre-long Visual Analogue Scale (VAS), and functional disability was measured by using the Indian version of the Health Assessment Questionnaire (HAQ). The disease activity was measured by Disease Activity Score for 28 joints with 3 variables. RESULTS: Probable anxiety and depression were seen in 61 (69%) and 68 (77%) of the patients, respectively. Patients with anxiety had more severe pain (VAS 53.8 ±26.4 vs. 39.7 ±26.1, p < 0.05), and significantly lower scores in all the 4 domains of the WHOQOL-BREF. Patients with depression had more pain (VAS 54.2 ±25.2 vs. 33.5 ±27.3, p < 0.01), higher HAQ scores (1.0 ±0.7 vs. 0.5 ±0.7, p < 0.01), and lower QOL scores. Both anxiety and depression scores had a negative correlation with all the 4 domains of the WHOQOL-BREF. Anxiety had a significant negative effect on psychological (β = -0.58, p < 0.001) and environmental domains (β = -0.39, p < 0.001), while depression had a significant negative effect on psychological (β = -0.57, p < 0.001) and environmental domains (β = -0.53, p < 0.001). Both anxiety and depression predicted more pain in RA patients (β = 0.24, p < 0.001 and β = 0.44, p < 0.001, respectively). CONCLUSIONS: Anxiety and depression correlated with poor QOL in all 4 domains of the WHOQOL-BREF. Higher HADS scores had a negative effect on all the domains of the WHOQOL-BREF and predicted more severe pain in RA patients. Thus, patients with RA need to be screened and treated for underlying anxiety and depression to improve their QOL, pain, and functional status.
34707695 Characterization of disease course and remission in early seropositive rheumatoid arthriti 2021 BACKGROUND: To characterise disease course and remission in a longitudinal observational study of newly diagnosed, initially treatment-naïve patients with seropositive rheumatoid arthritis (RA). METHODS: Patients with early untreated seropositive RA were recruited from 28 UK centres. Multiple clinical and laboratory measures were collected every 3 months for up to 18 months. Disease activity was measured using the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI). Logistic regression models examined clinical predictors of 6-month remission and latent class mixed models characterised disease course. RESULTS: We enrolled 275 patients of whom 267 met full eligibility and provided baseline data. According to SDAI definition, 24.3% attained 6-month remission. Lower baseline Health Assessment Questionnaire (HAQ) and SDAI predicted 6-month remission (p = 0.013 and 0.011). Alcohol intake and baseline prescribing of methotrexate with a second disease-modifying antirheumatic drug (DMARD; vs monotherapy without glucocorticoids) were also predictive. Three distinct SDAI trajectory subpopulations emerged; corresponding to an inadequate responder group (6.5%), and higher and lower baseline activity responder groups (22.4% and 71.1%). Baseline HAQ and Short Form-36 Health Survey - Mental Component Score (SF-36 MCS) distinguished these groups. In addition, a number of baseline clinical predictors correlated with disease activity severity within subpopulations. Beneficial effects of alcohol intake were found across subpopulations. CONCLUSION: Three distinct disease trajectory subpopulations were identified. Differential effects of functional and mental well-being, alcohol consumption, and baseline RA medication prescribing on disease activity severity were found across subpopulations. Heterogeneity across trajectories cannot be fully explained by baseline clinical predictors. We hypothesise that biological markers collected early in disease course (within 6 months) may help patient management and better targeting of existing and novel therapies.
34682784 Risk of Non-Vertebral Fracture in Gout Compared to Rheumatoid Arthritis. 2021 Oct 11 OBJECTIVE: To evaluate the risk of non-vertebral fractures in patients with gout compared with those with rheumatoid arthritis (RA). METHODS: Using claims data from Medicare (2008-2015), we conducted a cohort study of patients with gout versus RA matched on age, sex, and index date with a 1:1 ratio. The primary outcome was a composite endpoint of non-vertebral fractures including hip, pelvis, humerus, and wrist identified with the validated algorithms. We also assessed hip fractures separately. Multivariable Cox proportional hazards regression estimated the hazard ratio (HR) for the outcomes in gout versus RA adjusted for 45 covariates. RESULTS: We included a total of 134,157 matched pairs of gout and RA patients (mean age: 73.7 years). Risk factors for fracture were more prevalent in RA, while other comorbidities including obesity, coronary heart disease, hypertension, and diabetes were more common in gout. Over the mean 2.8 years follow-up, the incidence rate (IR)/1000 person-year (PY) of non-vertebral fractures was 10.42 in gout and 15.01 in RA. For hip fractures, the IR/1000 PY was 4.86 in gout and 7.73 in RA. The multivariable HR associated with gout versus RA was 0.84 (95% confidence interval (CI) 0.80-0.88) for non-vertebral fractures and 0.76 (95% CI 0.71-0.82) for hip fractures. Stratified analyses by age, sex, prior fractures, steroid use, and TNF inhibitor use showed similar results. CONCLUSIONS: In this large cohort of older patients, gout was associated with a modestly decreased risk of non-vertebral or hip fractures versus RA. However, non-vertebral fractures occurred frequently in both gout and RA.
34630505 No Causal Association Between Adiponectin and the Risk of Rheumatoid Arthritis: A Mendelia 2021 Background: Accumulating evidence from observational studies suggested that circulating adiponectin levels are associated with the risk of rheumatoid arthritis (RA), but the causality remains unknown. We aimed to assess the causal relationship of adiponectin with RA risk. Methods: Based on summary statistics from large-scale genome-wide association studies (GWAS), we quantified the genetic correlation between adiponectin and RA. Then bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship. Twenty single-nucleotide polymorphisms (SNPs) associated with adiponectin were selected as instrumental variables from a recent GWAS (n = 67,739). We applied theses SNPs to a large-scale GWAS for RA (14,361 cases and 43,923 controls) with replication using RA data from the FinnGen consortium (6,236 cases and 147,221 controls) and the UK Biobank (5,201 cases and 457,732 controls). The inverse-variance weighted (IVW) and multiple pleiotropy-robust methods were used for two-sample MR analyses. Results: Our analyses showed no significant genetic correlation between circulating adiponectin levels and RA [rG = 0.127, 95% confidence interval (CI): -0.012 to 0.266, P = 0.074]. In MR analyses, genetically predicted adiponectin levels were not significantly associated with the RA risk (odds ratio: 0.98, 95% CI: 0.88-1.09, P = 0.669). In the reverse direction analysis, there is little evidence supporting an association of genetic susceptibility to RA with adiponectin (β: 0.007, 95% CI: -0.003 to 0.018, P = 0.177). Replication analyses and sensitivity analyses using different models yielded consistent results. Conclusions: Our findings provided no evidence to support the causal effect of adiponectin levels on RA risk and of RA on circulating adiponectin levels.
34630103 Efficacy and Safety of Metformin Use in Rheumatoid Arthritis: A Randomized Controlled Stud 2021 Objective: To evaluate the efficacy and safety of metformin use in rheumatoid arthritis (RA) patients receiving conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). Methods: A prospective, randomized, controlled, single blinded, study was carried on 66 RA patients with moderate and high disease activity state, receiving csDMARDs. Patients were simply randomized to receive either metformin 850 mg twice daily (Metformin group, n = 33), or placebo twice daily (Control group, n = 33) in addition to their stable anti-rheumatic regimen and followed up for 6 months. Serum C-reactive protein (CRP), disease activity of 28 joints based on CRP (DAS-28-CRP), and quality of life (QOL) were evaluated at baseline and then every 3 months. Moreover, serum adiponectin was assessed at baseline and after 6 months. Results: Sixty patients completed the study. Drop out was due to intolerance to metformin side effects (n = 3) and non-compliance (n = 3). Metformin significantly decreased CRP levels and DAS-28-CRP after 6 months compared to the control group (p-value <0.001). A significant improvement in QOL of metformin group was observed as early as after 3 months (p-value = 0.006) with a continued improvement observed at 6 months (p-value <0.001) compared to the control group. Despite the significantly higher serum adiponectin in the metformin group at baseline, it was significantly reduced after 6 months in the metformin group with median percent change of -63.49% compared to the significant increase in the control group with median percent change of 92.40%. Conclusion: Metformin significantly improved inflammation, disease severity, and QOL in RA patients with high safety profile. Clinical Trial Registration: Clinical-Trials.gov, identifier [NCT08363405].
34447637 Exploring the role of monocyte chemoattractant protein-1 in fibroblast-like synovial cells 2021 BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease with persistent synovitis. In the present study, the impact of monocyte chemoattractant protein-1 (MCP-1) was explored to determine methods for the diagnosis and treatment of RA. METHODS: First, fibroblast-like synoviocytes (FLSs) were obtained from a collagen-induced rat RA model. Next, MCP-1-overexpression plasmid and small interfering RNA were transfected into human and rat FLSs. Cell Counting Kit-8 (CCK-8), Transwell migration and flow cytometry assays were used to analyze cell proliferation, migration and apoptosis of FLSs following MCP-1 transfections, respectively. Furthermore, western blotting was used to analyze the expression levels of p-P38, p-PI3K, PI3K, CD31, VEGF, TNF-α and IL-β in FLSs following MCP-1 transfection. In addition, reverse transcription-quantitative PCR and ELISAs were used to analyze the expression levels of C-reactive protein (CRP), estrogen receptor, MCP-1 and pentraxin-3 in patients with clinical RA, followed by correlation analysis of clinical data. Finally, expression validation, diagnostic and protein-protein interaction (PPI) network analysis of MCP-1 were performed. RESULTS: MCP-1 promoted FLS proliferation and migration, and affected the apoptosis of FLSs. In addition, the expression levels of p-P38, p-PI3K, PI3K, CD31, VEGF, TNF-α and IL-β were also affected by MCP-1. In patients with clinical RA, the expression level of MCP-1 was increased. Moreover, CRP expression level was significantly up-regulated in RA. Clinically, MCP-1 was strongly correlated with tender joint count, swollen joint count, visual analog scale for general health and disease activity score 28 (DAS28)-MCP-1, and was moderately correlated with DAS28 and DAS28-CRP. PPI analysis showed that MCP-1 mainly interacted with other inflammatory cytokines. CONCLUSION: In conclusion, MCP-1 may play a significant regulatory role in RA, and could be used as a measurement index of clinical RA activity.
33748370 Arthroplasty Rates Not Increasing in Young Patients With Rheumatoid Arthritis: A National 2021 Apr BACKGROUND: For 20 years, authors have predicted an expansion in total knee arthroplasty (TKA) and total hip arthroplasty (THA) utilization. Over this same period, the introduction of biological disease-modifying antirheumatic drugs has dramatically altered the treatment of rheumatoid arthritis (RA) with hopes of preventing articular damage and obviating the need for prosthetic replacement. The goal of our investigation was to evaluate TKA and THA utilization in young patients with RA (<65 years) in 2005 vs 2014 compared to patients with osteoarthritis (OA). METHODS: Using relevant International Classification of Disease Ninth Revision (ICD-9) and Current Procedural Terminology codes, the Truven MarketScan Database (over 46 million enrollees) was queried to determine THA and TKA incidence rates for RA and OA patients aged <65 years during the final decade of ICD-9 use. Patients with potentially confounding ICD-9 codes were excluded to limit coding variation. Statistical analysis consisted of student t-tests, Pearson's chi-square tests, and Breslow-Day tests. RESULTS: For patients with OA, TKAs increased substantially from 0.07% in 2005 to 0.1% in 2014 (+42.9% change, P < .001). Similarly for patients with OA, THAs increased from 0.04% to 0.06% over the same time period (+66.0% change, P < .001). For young patients with RA, the rate of TKA remained relatively stable-1.06% in 2005 to 1.04% in 2014 (-1.7% change, P = .65)-as did THA-0.44% to 0.48% (+9.0% change, P = .14). CONCLUSIONS: Dramatic increases in THA and TKA rates for OA patients aged <65 years were indeed observed from 2005 to 2014. This trend, however, was not seen in the RA population where TKA and THA rates remained unchanged.
34555681 Stress fracture of proximal tibia after proximal fibula osteotomy: A case report. 2021 Oct INTRODUCTION: Proximal fibula osteotomy (PFO) is a new method for treating medial compartment osteoarthritis of the knee, which is based on the theory of differential settlement (nonuniform settlement). This procedure has been widely recognized for its advantages of relative simplicity, low rate of postoperative complications, and low postoperative costs. Stress fracture of the proximal tibia after PFO has not been previously reported. CASE PRESENTATION: We report a 62-year-old woman with chronic rheumatoid arthritis (RA) underwent left PFO for chronic knee pain, who developed a stress fracture of the proximal tibia more than 1 year after PFO. CLINICAL DISCUSSION: In the early stage of proximal tibia stress fracture, due to the concealment of radiography manifestations, doctors from another hospital performed total knee arthroplasty (TKA) for the patient. They ignored the treatment of stress fracture of the proximal tibia, and the stress fracture was further aggravated after surgery. Six months later, the patient underwent open reduction and internal fixation with a plate and screw in the left proximal tibia fracture at our hospital. The patient was followed up at the hospital three months after open reduction, and the proximal tibia stress fracture began to heal. CONCLUSION: RA is usually not confined to the medial compartment and its pathogenesis is different from that of osteoarthritis. Therefore, PFO is not an appropriate procedure for this type of patient.
34484216 Alternative Splicing: A New Cause and Potential Therapeutic Target in Autoimmune Disease. 2021 Alternative splicing (AS) is a complex coordinated transcriptional regulatory mechanism. It affects nearly 95% of all protein-coding genes and occurs in nearly all human organs. Aberrant alternative splicing can lead to various neurological diseases and cancers and is responsible for aging, infection, inflammation, immune and metabolic disorders, and so on. Though aberrant alternative splicing events and their regulatory mechanisms are widely recognized, the association between autoimmune disease and alternative splicing has not been extensively examined. Autoimmune diseases are characterized by the loss of tolerance of the immune system towards self-antigens and organ-specific or systemic inflammation and subsequent tissue damage. In the present review, we summarized the most recent reports on splicing events that occur in the immunopathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and attempted to clarify the role that splicing events play in regulating autoimmune disease progression. We also identified the changes that occur in splicing factor expression. The foregoing information might improve our understanding of autoimmune diseases and help develop new diagnostic and therapeutic tools for them.
33824602 Potential Benefits of the Self-Administration of Subcutaneous Methotrexate with Autoinject 2021 The role of patient adherence in improving the efficacy of any treatment is widely accepted, as well as its impact in optimizing the use of healthcare resources and associated costs. Adherence is particularly affected in chronic conditions, such as rheumatoid arthritis (RA), requiring long-term therapies and a commitment of the patient to manage his/her disease. Methotrexate (MTX) is one of the mainstays of treatment for several immune-mediated inflammatory joint and skin diseases, especially RA. The use of parenteral MTX, particularly when administered as a subcutaneous (SC) injection, has recently raised a great interest to overcome the limitations of oral MTX. For addressing this issue, new optimized self-injection systems have been developed to improve the ease of use of SC MTX. Increasing evidence shows how patients tend to opt for autoinjectors over prefilled syringes or conventional syringes in terms of easiness of use, preference and satisfaction, regardless of whether the treatment is a biologic or MTX. Additionally, positive views and beliefs of patients about treatment may contribute to increasing expectations of effectiveness and treatment adherence. Similarly, the implementation of prefilled pens in clinical practice might be a way to facilitate and simplify the self-injection of SC MTX delivery, optimizing adherence and treatment outcomes as a consequence. This article aimed to review the available literature data on the use of MTX autoinjectors and their impact on treatment adherence and patients' perceptions.
33554027 Effusive-constrictive cholesterol pericarditis: a case report. 2021 Jan BACKGROUND: Cholesterol pericarditis (CP) remains a rare pericardial disease characterized by chronic pericardial effusions with high cholesterol concentrations with or without the formation of cholesterol crystals. Effusions are often large and can cause ventricular compression and subsequent pericardial adhesion formation. CP can be idiopathic but has associations with rheumatoid arthritis (RA), tuberculosis and hypothyroidism. CASE SUMMARY: We present a case of a 72-year-old male with a background of seropositive RA with a finding of an incidental pericardial effusion on computed tomography thorax abdomen and pelvis. Transthoracic echocardiogram demonstrated a large effusion with echocardiographic features of tamponade. On review, he was breathless with a raised venous pressure, bilateral ankle oedema, and pulsus paradoxus was present. Pericardial drainage was performed with fluid analysis demonstrating a cholesterol concentration of 8.3 mmol/L and numerous cholesterol crystal formation. Interval imaging demonstrated recurrence of the effusion with pericardial thickening and progressive constriction. He remained asymptomatic and underwent a successful pericardial window. At present, he is under close clinical outpatient surveillance with symptoms guiding a future pericardiectomy if warranted. DISCUSSION: CP can present as an emergent situation with signs and symptoms of acute heart failure with prompt pericardiocentesis required in cases of clinical tamponade. However, the disease course is often one of chronicity with relapsing large effusions that tend to recur following drainage, with the development of pericardial constriction necessitating pericardiectomy for definitive management.
34404491 No association between rheumatoid arthritis and cognitive impairment in a cross-sectional 2021 Aug 18 BACKGROUND: Studies suggest an increased prevalence of cognitive impairment (CI) among people with rheumatoid arthritis (RA). However, most prior studies have used convenience samples which are subject to selection biases or have failed to adjust for key confounding variables. We thus examined the association between CI and RA in a large national probability sample of older US adults. METHODS: Data were from interviews with 4462 participants in the 2016 wave of the nationally representative U.S. Health and Retirement Study with linked Medicare claims. RA diagnoses were identified via a minimum of two ICD-9CM or ICD-10 codes in Medicare billing records during the prior 2 years. The Langa-Weir Classification was used to classify cognitive status as normal, cognitively impaired non-dementia (CIND), or dementia based on a brief neuropsychological battery for self-respondents and informant reports for proxy respondents. We compared the odds of CI between older adults with and without RA using logistic regression, adjusted for age, education, gender, and race. RESULTS: Medicare records identified a 3.36% prevalence of RA (150/4462). While age, gender, education, and race independently predicted CI status, controlling for these covariates we found no difference in CI prevalence according to RA status (prevalent CI in 36.7% of older adults with RA vs. 34.0% without RA; adjusted OR = 1.08, 95% CI 0.74-1.59, p = .69). CONCLUSION: There was no association between RA and CI in this national sample of older U.S. adults.
34386702 Serum Calprotectin is Indicating Clinical and Ultrasonographic Disease Activity in Rheumat 2021 Mar OBJECTIVE: Calprotectin is an inflammatory biomarker which assesses disease activity in rheumatoid arthritis (RA). The objective of this study was to test whether serum calprotectin is associated with clinical and ultrasonographic disease activity in patients with RA, and to analyse its predicting value for disease activity evaluation despite normal C-Reactive protein (CRP) levels. METHODS: We included 80 patients with RA and 30 healthy subjects. Patients were examined clinically and by ultrasound, (US7 score) along with laboratory parameters (calprotectin, CRP, erythrocyte sedimentation rate [ESR]). Disease activity scores (DAS28) were calculated to assess disease activity. Firstly, patients were divided into four subgroups according to the DAS28-ESR (high, moderate, low disease activity, and remission), then into two subgroups; group-1 (DAS-28≤3.2) and group-2 (DAS28>3.2). The predicting value of calprotectin for disease activity in patients with normal CRP was analysed with univariate and multivariate analysis and receiver operating characteristic curves. RESULTS: Calprotectin levels were higher in RA patients than controls (96.3±45.9 ng/ml, 54.7±50.0 ng/ml, respectively; p<0.001). Calprotectin levels were 74.8±45.5 ng/ml in group-1 (n=37) and 114.7±37.9 ng/ml in group-2 (n=43) (p<0.001). In univariate analyses, calprotectin was significantly correlated with clinical, laboratory, and ultrasound parameters (p<0.05), and was a better predictor of power doppler synovitis than CRP in multivariate analysis (OR=1.014; 95%CI 1.002-1.027; p=0.024). The discriminatory capacity for calprotectin to distinguish ultrasonographically active disease in patients with normal CRP levels using AUC was 0.75 (95%CI 0.56-0.90, p=0.023). CONCLUSIONS: Calprotectin represents disease activity, even in patients who are clinical and ultrasonographical active but have normal CRP levels.
34268325 Methotrexate Reduces the Probability of Discontinuation of TNF Inhibitors in Seropositive 2021 Tumor necrosis factor inhibitors (TNFi) are widely used for the treatment of patients with rheumatoid arthritis (RA), however a considerable percentage of patients discontinued the therapy. The aim of this study is to explore real-world TNFi survival, stratified for seropositivity, and to determine the factors that may influence it. This is a retrospective, observational and longitudinal study, using real-world data of patients, who started their first TNFi therapy between 1999 and 2018 from the RA-PAZ cohort. Patients were considered seropositive if they showed positive serum levels of either RF, ACPA, or both. Treatment survival was analyzed using Kaplan-Meier curves, and Cox proportional hazards models were used to compare the risks of TNFi discontinuation for seronegative and seropositive patients. Of the included 250 patients, 213 (85%) were seropositive. Results showed that TNFi survival did not depend on seropositivity status. However, median survival time was significant longer for seropositive patients who received concomitant MTX compared to patients who did not receive it (median [95% CI]: 3.3 yr. [2.3-4.2] vs. 2.6 yr. [1.7-3.6], respectively; p = 0.008). Furthermore, seropositive patients who received concomitant MTX were 49% less likely to discontinue TNFi therapy than patients who did not receive it (HR: 0.51; 95% CI: 0.35-0.74). In addition, we found that in seropositive patients, the use of prednisone throughout the TNFi treatment was associated with a higher likelihood of therapy discontinuation (OR: 2.30; 95% CI: 1.01-5.23). In conclusion, these data provide evidence to support the use of concomitant MTX in seropositive patients to prolong the effectiveness and the survival of the TNFi therapy. Moreover, the co-administration of prednisone in seropositive patients receiving TNFi was highly associated with TNFi discontinuation.