Browse

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

ID PMID Title PublicationDate abstract
30993889 Care quality for rheumatoid arthritis patients in Quebec. 2019 Jul AIM: The aims of this study were to: (a) measure the proportion of CARTaGENE rheumatoid arthritis (RA) patients fulfilling pre-specified quality indicators (ie disease-modifying antirheumatic drug [DMARD] use, regular follow up, use of folate supplementation, use of vitamin D and calcium, exercise and smoking status); and (b) examine variation in DMARD use with respect to patient age, sex, education and income. METHODS: A cohort of RA patients was constructed based on the CARTaGENE survey and health administrative database. CARTaGENE is a large, established, population-based study which recruited 19 995 participants from four metropolitan regions in Quebec. Six quality indicators (QI) were assessed; four pertained to RA management and treatment received (use of DMARD therapy, annual medical visits, use of folate supplementation with methotrexate therapy, and use of calcium and vitamin D in steroid-exposed patients) and two pertained to lifestyle factors (physical activity and smoking cessation). QI were reported in terms of proportion of patients fulfilling them. Bayesian logistic regression analyses were preformed to investigate potential variation with DMARD use. RESULTS: Our cohort included 142 RA patients. The QI that pertain to RA pharmacotherapy and medical management ranged 60-80%. Regarding the QI focusing on lifestyle factors, 55% of patients reported performing moderate physical activity and only 16.6% reported current smoking. Results from the Bayesian logistic regression showed no definite associations between DMARD use and patient characteristics (age, education, income and sex). CONCLUSION: Our findings suggest a seemingly modest performance of Quebec's health-care system for RA patients, with respect to these QI.
31428089 Fibroblast-Like Synoviocytes Glucose Metabolism as a Therapeutic Target in Rheumatoid Arth 2019 Metabolomic studies show that rheumatoid arthritis (RA) is associated with metabolic disruption that may be therapeutically targetable. Among them, glucose metabolism and glycolytic intermediaries seem to have an important role in fibroblast-like synoviocytes (FLS) phenotype and might contribute to early stage disease pathogenesis. RA FLS are transformed from quiescent to aggressive and metabolically active cells and several works have shown that glucose metabolism is increased in activated FLS. Glycolytic inhibitors reduce not only FLS aggressive phenotype in vitro but also decrease bone and cartilage damage in several murine models of arthritis. Essential glycolytic enzymes, including hexokinase 2 (HK2) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB) enzymes, have important roles in FLS behavior. Of interest, HK2 is an inducible enzyme present only in the inflamed rheumatic tissues compared to osteoarthritis synovium. It is a contributor to glucose metabolism that could be selectively targeted without compromising systemic homeostasis as a novel approach for combination therapy independent of systemic immunosuppression. More information about metabolic targets that do not compromise global glucose metabolism in normal cells is needed.
31843000 Disease activity is associated with LV dysfunction in rheumatoid arthritis patients withou 2019 Dec 16 OBJECTIVES: The cross-sectional study aimed to assess left ventricular systolic function using global longitudinal strain (GLS) by speckle-tracking echocardiography (STE) and arterial stiffness using cardio-ankle vascular index (CAVI) in Thai adults with rheumatoid arthritis (RA) and no clinical evidence of cardiovascular disease (CVD). METHODS: Confirmed RA patients were selected from a list of outpatient attendees if they were 18 years (y) without clinical, ECG and echocardiographic evidence of CVD, diabetes mellitus, chronic kidney disease, and excess alcoholic intake. Controls were matched with age and sex to a list of healthy individuals with normal echocardiograms. All underwent STE and CAVI. RESULTS: 60 RA patients (females = 55) were analysed. Mean standard deviation of patient and control ages were 50 ± 10.2 and 51 ± 9.9 y, respectively, and mean duration of RA was 9.0 ± 6.8 y. Mean DAS28-CRP and DAS28-ESR were 2.9 ± 0.9 and 3.4 ± 0.9, respectively. There was no between-group differences in left ventricular ejection fraction (LVEF), LV sizes, LVMI, LV diastolic function and CAVI were within normal limits but all GLSs values was significantly lower in patients vs. controls: 17.6 ± 3.4 vs 20.4 ± 2.2 (p = 0.03). Multivariate regression analysis demonstrated significant correlations between GLSs and RA duration (p = 0.02), and GLSs and DAS28-CRP (p = 0.041). CONCLUSIONS: Patients with RA and no clinical CV disease have reduced LV systolic function as shown by lower GLSs. It is common and associated with disease activity and RA disease duration. 2D speckle-tracking GLSs is robust in detecting this subclinical LV systolic dysfunction.
31833613 Diosmetin exhibits anti-proliferative and anti-inflammatory effects on TNF-α-stimulated h 2020 Jun Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation and proliferation of synovial tissues. Diosmetin is a bioflavonoid possessing an anti-inflammatory property. Herein, we aimed to study the effects of diosmetin on the inflammation and proliferation of RA fibroblast-like synoviocytes MH7A cells. MH7A cell proliferation was measured using cell counting kit-8 assay. Cell apoptosis was examined using flow cytometry. The production of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, and matrix metalloproteinase-1 (MMP-1) was measured using enzyme-linked immunosorbent assay (ELISA). Results showed that diosmetin inhibited tumor necrosis factor-α (TNF-α)-induced proliferation increase in MH7A cells in a dose-dependent manner. Diosmetin treatment resulted in an increase in apoptotic rates and a reduction in TNF-α-induced production of IL-1β, IL-6, IL-8, and MMP-1 in MH7A cells. Furthermore, diosmetin inhibited TNF-α-induced activation of protein kinase B (Akt) and nuclear factor-κB (NF-κB) pathways in MH7A cells. Suppression of Akt or NF-κB promoted apoptosis and inhibited TNF-α-induced proliferation increase and production of IL-1β, IL-6, IL-8, and MMP-1 in MH7A cells, and diosmetin treatment enhanced these effects. Taken together, these findings suggested that diosmetin exhibited anti-proliferative and anti-inflammatory effects via inhibiting the Akt and NF-κB pathways in MH7A cells.
30560589 Associations between Health Assessment Questionnaire Disability Index and physical perform 2019 Mar OBJECTIVES: To investigate whether the Health Assessment Questionnaire Disability Index (HAQ-DI) reflects objective measures of physical function in people with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: In total, 139 people, 71 with RA fulfilling the American College of Rheumatology (ACR) criteria (1987) and 68 with OA fulfilling ACR criteria for OA of the hip or knee, completed the HAQ-DI. Physical function was assessed using Timed Up and Go (TUG), 30 seconds Sit to Stand (STS), grip strength dynamometry and pedometer steps over 7 days. RESULTS: The strongest association with HAQ-DI was with the TUG (R(2) of 0.671 and 0.512 in RA and OA groups, respectively). HAQ-DI and STS showed a non-linear association in both groups with R(2) of 0.380 in RA and 0.359 in OA. A strong association was found between HAQ-DI and grip strength in the OA group (R(2)  = 0.681), whereas the RA group showed a moderate association (R(2)  = 0.285). There was a strong association between the HAQ-DI and pedometer measures in RA (R(2)  = 0.562), although this association was weak in OA (R(2)  = 0.156). CONCLUSION: The HAQ-DI has a strong association with the TUG in both RA and OA. There was variable association between the HAQ-DI and other physical performance measures, as well as differences between the RA and OA cohorts. In order to form a full and accurate clinical picture, health professionals should perform both subjective patient-reported outcome measures and objective physical performance measures of disability.
31729189 Safety of baricitinib in East Asian patients with moderate-to-severe active rheumatoid art 2020 Jan AIM: We evaluated the safety of baricitinib in an East Asian (EA) patient population with moderate-to-severely active rheumatoid arthritis (RA), through an integrated sub-analysis of data from the overall baricitinib RA clinical program. METHODS: Data from EA patients who received any dose of baricitinib from five completed studies (1 Phase 2, 4 Phase 3) and an ongoing long-term extension study were pooled up to 1 September, 2016. Exposure-adjusted incidence rates (EAIR) and incidence rates (IRs), both per 100 patient-years (PY), were calculated. RESULTS: This analysis included 740 EA patients with 1294 PY of total baricitinib exposure (maximum 3.5 years). Overall, 109 patients discontinued baricitinib due to adverse events (AEs); EAIR: 8.4. No deaths were reported in this cohort. Serious AEs were reported by 125 patients (EAIR: 9.7). Serious infections were the most common serious AEs (n = 53, IR: 4.15). IR of herpes zoster infection was 6.2; the majority of events were of mild-to-moderate severity. Three cases (IR: 0.23) of tuberculosis were reported. The IRs of malignancy (excluding non-melanoma skin cancer) was 0.99 and EAIR specifically of lymphoma was 0.1. The IR of major adverse cardiovascular events was 0.26, and deep vein thrombosis was reported in four patients (EAIR: 0.3). Two cases of gastrointestinal perforations (EAIR: 0.2) were reported. CONCLUSION: Integrated data show that baricitinib is well-tolerated in EA patients with moderate-to-severely active RA in the context of demonstrated efficacy, which is generally consistent with safety results of the overall study population.
30753709 Routine musculoskeletal ultrasound findings impact diagnostic decisions maximally in autoa 2019 Jul 1 OBJECTIVE: The diagnostic value added by musculoskeletal ultrasound (MSUS) over standard clinical and laboratory parameters has proved difficult to quantify. The additive contribution to diagnostic classification of a pragmatic, 15 min MSUS protocol was appraised in a large, unselected cohort of early arthritis clinic attendees. METHODS: Detailed baseline characteristics were recorded. Semi-quantitative MSUS scoring of the most symptomatic wrist, second/third MCPs and PIPs and second/fifth MTPs was recorded, along with the sonographer's scan impression (definitely inflammatory, possibly inflammatory or non-inflammatory). MSUS findings were available to rheumatologist diagnosticians during subsequent consultations. Persistent inflammatory arthritis (PIA) was classified only where patients were started on ≥1 DMARD. Multivariate and receiver operating characteristic (ROC) curve analyses were used to identify independent discriminators of PIA, and the added value of MSUS parameters. RESULTS: Eight hundred and thirty-one patients were enrolled, of whom 31.3% acquired a PIA diagnosis. Swollen joint count, CRP, age and ACPA status were non-redundant clinical/laboratory predictors of a PIA diagnosis by consulting rheumatologists, with good discriminatory utility (area under the ROC curve, AUROC, 0.88). While the additive contribution of summed parameters from the seven-joint MSUS protocol to this model was statistically significant (P = 0.004), it was numerically small (ΔAUROC 0.02). However, the additive contribution to diagnostic outcome of sonographer's scan impression over clinical parameters alone became substantial in the sub-cohort of ACPA-negative patients, increasing the AUROC by 9% from 0.81 to 0.90 (P < 0.0001). CONCLUSION: The clinical utility of a 15-min MSUS screen for diagnosing PIA requiring DMARDs is most evident among ACPA-negative patients attending an early arthritis clinic.
30656490 Occurrence of anti-CCP2 and RF isotypes and their relation to age and disease severity amo 2019 Jun OBJECTIVE: Anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2) and rheumatoid factor (RF) in rheumatoid arthritis (RA) has been extensively assessed in industrialized countries. We investigated the diagnostic and prognostic impact of anti-CCP2 and RF isotypes in a Sudanese cross-sectional RA cohort. METHODS: Consecutive RA patients (n = 281) diagnosed according to the 1987 ACR criteria were included 2008-2010. Anti-CCP2 and RF isotypes (IgA, IgM, and IgG) were measured by enzyme immunoassay in 262 patients, with reference intervals aligned to the same diagnostic specificity as for anti-CCP2 (97.6%) using national controls. RESULTS: IgA RF was the predominant RA-associated autoantibody (56%), followed by IgM RF and anti-CCP2 (both 52%) and IgG RF (49%). In receiver operator characteristic analysis, IgA RF also showed the largest area under the curve. Patients with IgG RF were younger and had 8 years lower median age of disease onset compared to antibody negative patients (p < 0.0001). IgG RF was the only marker associated with a high number of involved joints (p = 0.028), and together with anti-CCP2 were the strongest markers for finger deformities (p = 0.016 and p = 0.012), respectively. No statistical differences were found for disease duration, ESR and Hb levels, and occurrence of erosions/osteopenia for any of the investigated autoantibodies. CONCLUSION: Whereas IgA RF showed the best diagnostic performance, IgG RF associated with low age of RA onset, high number of involved joints, and finger deformities. These findings indicate that RA-associated antibodies other than conventional IgM RF and anti-CCP2 might be informative in non-Caucasian RA populations.
30649521 Impact of TNF inhibitor therapy on joint replacement rates in rheumatoid arthritis: a matc 2019 Jul 1 OBJECTIVES: Previous ecological data suggest a decline in the need for joint replacements in RA patients following the introduction of TNF inhibitor (TNFi) therapy, although patient-level data are lacking. Our primary aim was to estimate the association between TNFi use and subsequent incidence of total hip replacement (THR) and total knee replacement. METHODS: A propensity score matched cohort was analysed using the British Society for Rheumatology Biologics Registry (2001-2016) for RA data. Propensity score estimates were used to match TNFi users to similar conventional synthetic DMARD users (with replacement) using a 1:1 ratio. Weighted multivariable Cox regression was used to estimate the impact of TNFi on study outcomes. Effect modification by baseline age and disease severity were investigated. Joint replacement at other sites was also analysed. An instrumental variable sensitivity analysis was also performed. RESULTS: The matched analysis contained a total of 19 116 patient records. Overall, there was no significant association between TNFi use vs conventional synthetic DMARD on rates of THR (hazard ratios = 0.86 [95% CI: 0.60, 1.22]) although there was significant effect modification by age (P < 0.001). TNFi was associated with a reduction in THR among those >60 years old (hazard ratio = 0.60 [CI: 0.41, 0.87]) but not in younger patients. No significant associations were found for total knee replacement or other joint replacement. CONCLUSION: Overall, no association was found between the use of TNFi and subsequent incidence of joint replacement. However, TNFi was associated with a 40% relative reduction in THR rates among older patients.
31088790 Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheuma 2019 Aug OBJECTIVES: To investigate the effect of Janus kinase inhibitors (Jakinibs) on cardiovascular risk in adult patients with rheumatoid arthritis (RA) via a meta-analysis of randomised controlled trials (RCTs). METHODS: PubMed, Embase and Cochrane library were thoroughly searched for RCTs reporting safety issues in patients with RA receiving Jakinibs, from inception to October 2018. The primary and secondary outcomes were all cardiovascular events (CVEs) and major adverse cardiovascular events (MACEs)/venous thromboembolism events (VTEs). OR and 95% CI were calculated using the Mantel-Haenszel fixed-effect method. RESULTS: 26 RCTs randomising 11 799 patients were included. No significant difference was observed regarding all CVEs risk following Jakinibs usage in general (OR 1.04 (0.61 to 1.76), p = 0.89), tofacitinib (OR 0.63 (0.26 to 1.54), p = 0.31), baricitinib (OR 1.21 (0.51 to 2.83), p = 0.66), upadacitinib (OR 3.29 (0.59 to 18.44), p = 0.18), peficitinib (OR 0.43 (0.07 to 2.54), p = 0.35) or decernotinib (OR 1.12 (0.13 to 10.11), p = 0.92). Likewise, there was no significant difference for Jakinibs treatment overall regarding occurrence of MACEs (OR 0.80 (0.36 to 1.75), p = 0.57) or VTEs (OR 1.16 (0.48 to 2.81), p = 0.74). Dose-dependent impact of Jakinibs on the risks of all CVEs, MACEs and VTEs was not observed in tofacitinib (5 mg vs 10 mg), upadacitinib (15 mg vs 30 mg), whereas baricitinib at 2 mg was found to be safer than 4 mg in all CVEs incidence (OR 0.19 (0.04 to 0.88), p = 0.03). CONCLUSION: The existing evidence from RCTs indicated no significant change in cardiovascular risk for Jakinib-treated patients with RA in a short-term perspective, but postmarketing data are sorely needed to ascertain their cardiovascular safety, especially at the higher dose, due to increased risk of thromboembolism events for both tofacitinib and baricitinib at higher dosage.
30671749 A survey of traditional Chinese medicine use among rheumatoid arthritis patients: a claims 2019 May INTRODUCTION/OBJECTIVES: Traditional Chinese medicine (TCM) is commonly used for symptom relief in patients with chronic diseases. Nevertheless, large-scale surveys focusing on the utilization of TCM among patients with rheumatoid arthritis (RA) are limited, especially in Taiwan, where TCM is highly popular. This cohort study aimed to describe the utilization of TCM and determine the factors related to TCM usage among RA patients. METHOD: A national health insurance database was used to identify 6532 newly diagnosed RA patients aged between 20 and 70 years, together with 12,246 subjects without RA matched by sex, age, and index year between 2000 and 2010. Incidence density of TCM use and its related factors was calculated by the Poisson regression model. RESULTS: Findings indicated that RA patients experienced higher incidence density of TCM use than non-RA patients, with an adjusted incidence density ratio of 1.30 (95% confidence interval = 1.21-1.36). Multivariate analysis showed that RA patients who were female, were young, had high monthly income, had high Charlson-Deyo comorbidity index scores, and lived in the highly urbanized area with high TCM density were more likely to use TCM services. The top three reasons for seeking TCM services were diseases of the musculoskeletal system and connective tissue, the respiratory system, and the digestive system. CONCLUSIONS: The findings allow healthcare providers to identify the pattern of TCM use and characterize the factors that affect TCM utilization. Further research is required to fully address the efficiency and safety of TCM in treating RA patients.
31326541 Industry funding was associated with increased use of core outcome sets. 2019 Nov OBJECTIVES: The objective of this study was to assess the uptake of the rheumatoid arthritis core outcome set (RA-COS) using data from multiple data providers, and to investigate factors that may influence this uptake. STUDY DESIGN AND SETTING: An observational review was carried out on all clinical trials of rheumatoid arthritis that were indexed on the World Health Organization-International Clinical Trials Registry Platform (WHO-ICTRP). Various measures of COS uptake were calculated from information presented in the trial registries and trial publications. Logistic regression was conducted to investigate factors thought to be associated with planned COS uptake. RESULTS: A total of 341 trials were eligible for the evaluation of RA-COS uptake. In the decade leading up to 2019, the assessment of uptake based on published results was maintained at just over 80%. Trials that were not commercially funded were much less likely to plan to measure the RA-COS than those with industry funding (60% vs. 80%; adjusted OR 0.18, 95% CI 0.11 to 0.32; P < 0.001). CONCLUSION: This study has demonstrated that the use of the WHO-ICTRP can identify a large and geographically diverse range of trials to include in the evaluation of COS uptake.
30701418 Selective JAKinibs: Prospects in Inflammatory and Autoimmune Diseases. 2019 Feb Cytokines, many of which signal through the JAK-STAT (Janus kinase-Signal Transducers and Activators of Transcription) pathway, play a central role in the pathogenesis of inflammatory and autoimmune diseases. Currently three JAK inhibitors have been approved for clinical use in USA and/or Europe: tofacitinib for rheumatoid arthritis, psoriatic arthritis and ulcerative colitis, baricitinib for rheumatoid arthritis, and ruxolitinib for myeloproliferative neoplasms. The clinical JAK inhibitors target multiple JAKs at high potency and current research has focused on more selective JAK inhibitors, almost a dozen of which currently are being evaluated in clinical trials. In this narrative review, we summarize the status of the pan-JAK and selective JAK inhibitors approved or in clinical trials, and discuss the rationale for selective targeting of JAKs in inflammatory and autoimmune diseases.
31858963 Tofacitinib in combination with methotrexate in patients with rheumatoid arthritis: patien 2020 Sep OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we present data from the completed Phase 3 randomised controlled trial (RCT) ORAL Scan (NCT00847613), which evaluated the impact of tofacitinib on patient-reported outcomes (PROs) through 24 months in patients with active RA and inadequate responses to methotrexate (MTX-IR). METHODS: Patients were randomised 4:4:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID), or placebo advanced to tofacitinib 5 or 10 mg, plus background MTX. Patients receiving placebo advanced to tofacitinib at month 3 (non-responders) or month 6 (remaining patients). Mean changes from baseline in PROs, assessed at months 1-24, included Health Assessment Questionnaire-Disability Index, Patient Global Assessment of disease activity (visual analogue scale [VAS]), Patient Assessment of Arthritis Pain (VAS), health-related quality of life (Short Form-36 version 2), Functional Assessment of Chronic Illness Therapy-Fatigue and Medical Outcomes Study-Sleep. RESULTS: Overall, 539/797 (67.6%) patients completed 24 months' treatment. At month 3, tofacitinib-treated patients reported signi cant (p<0.05) mean changes from baseline versus placebo across all PROs, and significantly more patients reported improvements ≥ minimum clinically important differences versus placebo. Improvements in PROs with tofacitinib were sustained to month 24. Following advancement to tofacitinib, placebo-treated patients generally reported changes of similar magnitude to tofacitinib-treated patients. CONCLUSIONS: Patients with RA and MTX-IR receiving tofacitinib 5 or 10 mg BID plus MTX reported significant and clinically meaningful improvements in PROs versus placebo at month 3, which were sustained through 24 months.
30459097 Cluster analysis of autoimmune rheumatic diseases based on autoantibodies. New insights fo 2019 Mar Autoimmune diseases (ADs) are a chronic and clinically heterogeneous group of diseases characterized by share common immunopathogenic mechanisms and risk factors (i.e., the autoimmune tautology), which explain the fact that one AD may coexist with others (i.e., polyautoimmunity - PolyA). In the present exploratory study, a mixed-cluster analysis of the most common autoimmune rheumatic diseases (ARDs) was done. A total of 187 consecutive women with established systemic lupus erythematosus (n = 70), rheumatoid arthritis (n = 51), systemic sclerosis (n = 35) and Sjögren's syndrome (n = 31) were included. A comprehensive clinical, autoantibody and cytokine assessment was simultaneously done. Total PolyA was registered in 142 (75.9%) patients. Six clusters were obtained, built mainly on autoantibodies: PolyA-I to -VI. The PolyA-III cluster showed the highest frequency of overt PolyA (p = 0.01), and the PolyA-I, -III, and -IV clusters exhibited the highest positivity for IL-12/23p40 (p = 0.015). These results provide new insights into the pathophysiology of PolyA and warrant prospective validation to enable development of a more accurate taxonomy of ARDs.
31244849 Kirenol Inhibits the Function and Inflammation of Fibroblast-like Synoviocytes in Rheumato 2019 Kirenol is a diterpenoid extracted from the Chinese herbal medicine Siegesbeckiae. Siegesbeckiae has been used to treat Rheumatoid arthritis (RA) in China for several centuries. RA is characterized by the proliferation of synoviocytes in inflamed synovia, as well as by their expression of inflammatory cytokines. In the present study, we found that Kirenol inhibited the migration, invasion, and proinflammatory of IL-6 secretion of RA-associated synovial fibroblasts (FLS) at a concentration of 100-200 μg/ml in vitro. Proinflammatory cytokines production and synovium hyperplasia and cartilage erosion were also inhibited in a collagen-induced arthritis (CIA) mouse model upon Kirenol treatment. Together, our results thus confirm that Kirenol has potent therapeutic efficacy in RA owing to its ability to suppress negative FLS activities.
31717450 Factors Associated With Low Lean Mass in Early Rheumatoid Arthritis: A Cross- Sectional St 2019 Nov 8 Background and Objectives: The aim of the study was to evaluate body composition (BC) of rheumatoid arthritis (RA) patients at disease onset compared to population controls focusing on the associations between low lean mass and disease specific parameters, nutritional factors and physical activity. Materials and Methods: 91 patients with early rheumatoid arthritis (ERA) (72% female) and 328 control subjects (54% female) were studied. BC- lean and fat mass parameters were measured with a Lunar Prodigy Dual Energy X-Ray Absorptiometry (DXA) machine. The prevalence, age and gender adjusted odds ratios of having low lean mass and overfat, associations between nutrition, physical activity, and ERA disease specific parameters and the presence of low lean mass were evaluated. Results: We found that the BC of patients with recent onset RA differs from control subjects-ERA patients had a higher mean body fat percentage (BFP) and lower appendicular lean mass (ALM). 41.8% of the ERA patients and 19.8% of the controls were classified as having low lean mass adjusted OR 3.3 (95% C.I. 1.9-5.5, p < 0.001). 68.1% of the ERA subjects and 47.3% of the controls were overfat (adjusted OR 1.9 (95% C.I. 1.1-3.3, p = 0.02)) and the adjusted odds of having both low lean mass and overfat were 4.4 times higher (26.4% vs. 7.0% 95% C.I. 2.3-8.4, p < 0.001) among the ERA group. Higher ESR (OR 1.03, C.I.1.002-1.051, p = 0.03), CRP (OR 1.03, C.I. 1.002-1.061, p = 0.04), lower protein intake (OR 0.98 C.I. 0.96-0.99, p = 0.04), corticosteroid usage (OR 3.71 C.I. 1.4-9.9, p < 0.01) and lower quality of life (higher HAQ score OR 2.41 C.I. 1.24-4.65, p < 0.01) were associated with having low lean mass in the ERA group (adjusted to age and gender). Conclusions: Patients with early RA have lower appendicular lean mass and higher body fat percentage compared to healthy controls. Loss of lean mass in early RA is associated with elevated inflammatory markers inducing catabolism, lower protein intake and also with GCS treatment.
31464042 Timing of Elevations of Autoantibody Isotypes Prior to Diagnosis of Rheumatoid Arthritis. 2020 Feb OBJECTIVE: To evaluate patterns of elevations of isotypes of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) pre-rheumatoid arthritis (RA) diagnosis and post-RA diagnosis. METHODS: Using the Department of Defense Serum Repository we identified 214 RA cases and 210 matched controls. Up to 3 pre-RA diagnosis and 1 post-RA diagnosis serum samples per subject were tested for RF and for IgA, IgG, and IgM ACPAs. The timing and trajectories of elevations of autoantibodies were evaluated. RESULTS: Autoantibody levels were elevated in cases versus controls a mean of 17.9 years before RA diagnosis for IgG ACPA, 14.2 years for IgA-RF, 7.2 years for IgM-RF, 6.2 years for IgA ACPA, and 5.0 years for both IgM ACPA and IgG-RF (P < 0.01 for all comparisons). There were similar relationships for positive or negative autoantibody status, with cases first showing positivity for IgG ACPA 1.9 years pre-RA and for IgA-RF 1.7 years pre-RA, followed by the other isotypes. Only IgA ACPA positivity was significantly increased in post-RA diagnosis samples (19% 0-2 years pre-RA versus 39% >2 years post-RA diagnosis; P = 0.04). All autoantibody levels demonstrated an early initial elevation, a period of stability, then an increase immediately before RA diagnosis. A pre-RA endotype of early elevation of autoantibodies was associated with increased use of biologic therapy, and a higher prevalence of sicca symptoms and lung disease post-RA diagnosis. CONCLUSION: Differences in patterns of elevations of autoantibody isotypes have implications for understanding the pathophysiology of RA development. These include understanding what factors drive initial autoantibody elevations compared to what factors (including mucosal) drive later increases in autoantibody levels and a transition to clinically apparent RA, and how pre-RA endotypes may influence post-RA diagnosis phenotypes.
31366796 Inflammatory Cerebellar PML with a CD4/CD8 Ratio of 2.9 Showed a Favorable Prognosis in a 2019 Nov 15 The patient was a 74-year-old woman with rheumatoid arthritis who developed ataxia. MRI revealed T2-hyperintense lesions predominantly in the left middle cerebellar peduncle. Punctate or linear Gd enhancement was also observed on T1-weighted images. A brain biopsy was conducted and the pathology revealed a mild demyelinated lesion. Polymerase chain reaction (PCR) of biopsied brain tissues revealed the presence of JC virus (JCV) DNA, but JCV-infected oligodendroglia-like cells were not apparent on immunohistochemistry. Sensitive in-situ hybridization, however, detected three JCV-positive cells and the infiltration of CD4(+) and CD8(+) T cells and plasma cells was also observed. Immunosuppressants were tapered off and mirtazapine and mefloquine administered, resulting in a favorable outcome.
30879707 Joint Mobilization of the Hands of Patients With Rheumatoid Arthritis: Results From an Ass 2019 Jan OBJECTIVE: The purpose of this study was to assess the clinical feasibility and effectiveness of manual mobilization of the hands of patients with rheumatoid arthritis (RA). METHODS: A total of 320 individual hand joints were evaluated after recruiting an experimental research group of 12 participants with RA and, for clinical comparability, 8 participants with hand osteoarthritis (OA). One hand per participant was randomized to receive weekly low-grade (I-II) Kaltenborn manual mobilization, using passive sustained stretch of the metacarpophalangeal (MCP) joints II to V by licensed manual therapists. After 2 weeks, the randomized treated hand was crossed over to control (untreated) during weeks 3 to 4 and vice versa. Final assessment was at 2 months, which was 1 month after the last treatment at week 4. Primary hand outcomes included pain by visual analog scale, tender or swollen joint count, and presence of Doppler signal or synovial fluid and radiographic joint space by musculoskeletal ultrasound. RESULTS: In the RA group, both the initially randomized treated hand and the contralateral hand improved significantly from baseline to crossover to follow-up at 2 months (pain outcomes and Doppler signal, P < .050; synovial fluid and MCP joint space, P ≤ .001). Hand pain and MCP joint space also improved significantly in OA. There were no dropouts or reported adverse events in either the RA or OA group. CONCLUSION: In this study, manual mobilization of the hands of patients with RA was shown to be feasible, safe, and effective to integrate into specialized healthcare.