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ID PMID Title PublicationDate abstract
28992379 Association Between Anti-Citrullinated Fibrinogen Antibodies and Coronary Artery Disease i 2018 Jul OBJECTIVE: Antibodies against citrullinated fibrinogen (anti-Cit-fibrinogen) have been implicated in rheumatoid arthritis (RA) and associated with cardiovascular risk in RA. The objective of this study was to examine the association between anti-Cit-fibrinogens and coronary artery disease (CAD) outcomes. METHODS: We performed the study in an RA cohort based in a large academic institution linked with electronic medical record data containing information on CAD outcomes from medical record review. Using a published bead-based assay method, we measured 10 types of anti-Cit-fibrinogens. We applied a score test to determine the association between the anti-Cit-fibrinogens as a group with CAD outcomes. Principal components analysis (PCA) was performed to assess whether the anti-Cit-fibrinogens clustered into groups. Each group was then additionally tested for association with CAD. Sensitivity analyses were also performed using a published International Classification of Disease, Ninth Revision code group for ischemic heart disease (IHD) as the outcome. RESULTS: We studied 1,006 RA subjects (mean ± SD age 61.0 ± 13.0 years; 72.2% anti-cyclic citrullinated peptide positive). As a group, anti-Cit-fibrinogen was associated with CAD (P = 1.1 × 10(-4) ). From the PCA analysis, we observed 3 main groups, of which only 1 group, containing 7 of the 10 anti-Cit-fibrinogens, was significantly associated with CAD outcomes (P = 0.015). In the sensitivity analysis, all anti-Cit-fibrinogens as a group remained significantly associated with IHD (P = 2.9 × 10(-4) ). CONCLUSION: Anti-Cit-fibrinogen antibodies as a group were associated with CAD outcomes in our RA cohort, with the strongest signal for association arising from a subset of the autoantibodies.
30175554 Influence of pain score measured by a visual analog scale (PS-VAS) on the Health Assessmen 2018 Nov BACKGROUND: Pain is a serious burden for rheumatoid arthritis (RA) patients. However, the effect on Health Assessment Questionnaire Disability Index (HAQ-DI) and 28-joint Disease Activity Score (DAS28) has not been presented. The aim of this study is to evaluate them in a case series. METHODS: Three hundred and eighty-two RA patients who were treated for more than 5 years were studied. The parameters assessed included average value of the DAS28 with C-reactive protein (DAS28-CRP), the HAQ-DI score, the Sharp/van der Heijde Score (SvdHS), age, and the pain score measured by a visual analog scale (PS-VAS). Relationships among these factors and the relationships between the HAQ-DI score and the other factors, and the relationships between the change in HAQ-DI scores and the changes in other factors were evaluated statistically with multivariate linear regression analysis. The effect of PS-VAS on HAQ-DI was compared with that of DAS28-CRP on the overlapping data of each parameter. RESULTS: HAQ-DI demonstrated significant positive correlations with all parameters. However, PS-VAS demonstrated a stronger effect than DAS28-CRP, also demonstrated without overlapping data. After minimizing the effects of DAS28-CRP, age and SvdHS, there was a significant correlation between HAQ-DI and PS-VAS in all analyses. The change in HAQ-DI demonstrated a significant correlation with the change in PS-VAS. CONCLUSIONS: These results suggested that HAQ-DI is deeply influenced by PS-VAS. The effect of DAS28-CRP overlapped with the effect of PS-VAS in a major way. Pain control for RA patients is the most important factor contributing to activities of daily living, as well as disease activity control.
29422289 Prevalence and Effects of Emphysema in Never-Smokers with Rheumatoid Arthritis Interstitia 2018 Feb AIMS: Autoimmune conditions such as rheumatoid arthritis-related interstitial lung disease (RA-ILD) have been linked to the existence of emphysema in never-smokers. We aimed to quantify emphysema prevalence in RA-ILD never-smokers and investigate whether combined pulmonary fibrosis and emphysema (CPFE) results in a worsened prognosis independent of baseline disease extent. METHODS: RA-ILD patients presenting to the Royal Brompton Hospital (n=90) and Asan Medical Center (n=155) had CT's evaluated for a definite usual interstitial pneumonia (UIP) pattern, and visual extents of emphysema and ILD. RESULTS: Emphysema, identified in 31/116 (27%) RA-ILD never-smokers, was associated with obstructive functional indices and conformed to a CPFE phenotype: disproportionate reduction in gas transfer (DLco), relative preservation of lung volumes. Using multivariate logistic regression, adjusted for patient age, gender and ILD extent, emphysema presence independently associated with a CT-UIP pattern in never-smokers (0.009) and smokers (0.02). On multivariate Cox analysis, following adjustment for patient age, gender, DLco, and a CT-UIP pattern, emphysema presence (representing the CPFE phenotype) independently associated with mortality in never-smokers (p=0.04) and smokers (p<0.05). CONCLUSION: 27% of RA-ILD never-smokers demonstrate emphysema on CT. Emphysema presence in never-smokers independently associates with a definite CT-UIP pattern and a worsened outcome following adjustment for baseline disease severity.
29720256 Inflammation functions as a key mediator in the link between ACPA and erosion development: 2018 May 3 BACKGROUND: Anti-citrullinated protein antibodies (ACPA) are associated with more severe joint erosions in rheumatoid arthritis (RA), but the underlying mechanism is unclear. Recent in vitro and murine studies indicate that ACPAs can directly activate osteoclasts leading to bone erosions and pain. This study sought evidence for this hypothesis in humans and evaluated whether in patients with arthralgia who are at risk of RA, ACPA is associated with erosions (detected by magnetic resonance imaging (MRI)) independent of inflammation, and also independent of the presence of rheumatoid factor (RF). METHODS: Patients with Clinically Suspect Arthralgia (n = 507) underwent determination of ACPA and RF and 1.5 T contrast-enhanced MRI of the metacarpophalangeal, wrist and metatarsophalangeal joints at baseline. MRIs were scored for presence of local inflammation and erosions. Comparisons of erosion scores were performed using the Kruskal-Wallis test. To evaluate if inflammation is, in statistical terms, intermediary in the causal path of ACPA and erosions, three-step mediation analysis was performed using linear regression. RESULTS: ACPA-positive patients had higher erosion scores than ACPA-negative patients (p = 0.006). ACPA-positive patients without subclinical inflammation did not have higher erosion scores than ACPA-negative patients (p = 0.68), in contrast to ACPA-positive patients with local inflammation (p < 0.001). Mediation analyses suggested that local inflammation is in the causal path of ACPA leading to higher erosion scores. Compared to ACPA-negative/RF-negative patients, ACPA-positive/RF-negative patients did not differ (p = 0.30), but ACPA-positive/RF-positive patients had higher erosion scores (p = 0.006). CONCLUSIONS: The effect of ACPA on erosions is mediated by inflammation and is not independent of RF.
29888580 [Treatment of Rheumatoid Arthritis by Bee-venom Acupuncture]. 2018 Apr 25 OBJECTIVE: To study the clinical efficacy and safety of bee-venom acupuncture therapy for rheumatoid arthritis (RA). METHODS: A total of 120 cases of RA patients were randomized into bee-sting acupuncture group (treatment) and western medicine group (control) in accordance with the random number table. The patients of the control group were treated by oral administration of Methotrexate (10 mg, once a week) and Celecoxlb (0.2 g, once a day), and those of the treatment group treated by 5 to 15 bee stings of Ashi-points or acupoints according to different conditions and corporeity, and with the bee-sting retained for about 5 min every time, once every other day. The treatment lasted for 8 weeks. The therapeutic effect was assessed by examining symptoms and signs of the affected joints as morning stiffness duration, swollen/tender joint counts (indexes), handgrip strength, 15 m-walking time, visual analogue scale (VAS), Disease Activity Score including a 28-joint count (DAS 28), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibody (ACCPA); and for assessing the safety of bee-venom acupuncture, the patients' responses of fever, enlargement of lymph nodes, regional red and swollen, itching, blood and urine tests for routine were examined. RESULTS: Findings of DAS 28 responses displayed that of the two 60 cases in the control and bee-venom acupuncture groups, 15 and 18 experienced marked improvement, 33 and 32 were effective, 12 and 10 ineffective, with the effective rates being 80% and 83. 33%, respectively. No significant difference was found between the two groups in the effective rate (P>0.05). After the treatment, both groups have witnessed a marked decrease in the levels of morning stiffness duration, arthralgia index, swollen joint count index, joint tenderness index, 15 m walking time, VAS, RF, ESR, CRP and ACCPA, and an obvious increase of handgrip strength relevant to their own levels of pre-treatment in each group (P<0.05). There were no significant differences between the two groups in the abovementioned indexes (P>0.05). The routine blood test, routine urine test, routine stool test, electrocardiogram result, the function of liver and kidney and other security index were within the normal range, without any significant adverse effects found after bee-stinging treatment. CONCLUSION: Bee-venom acupuncture therapy for RA patients is safe and effective, worthy of popularization and application in clinical practice.
28426913 Body Mass Index, Weight Loss, and Cause-Specific Mortality in Rheumatoid Arthritis. 2018 Jan OBJECTIVE: To examine associations of body mass index (BMI) and weight loss with cause-specific mortality in rheumatoid arthritis (RA). METHODS: A cohort of US veterans with RA was followed until death or through 2013. BMI was categorized as underweight, normal, overweight, and obese. Weight loss was calculated as the 1) annualized rate of change over the preceding 13 months, and 2) cumulative percent. Vital status and cause of death were obtained from the National Death Index. Multivariable competing-risks regression models were utilized to assess the time-varying associations of BMI and weight loss with cause-specific mortality. RESULTS: Among 1,600 participants and 5,789 patient-years of followup, 303 deaths occurred (95 cardiovascular, 74 cancer, and 46 respiratory). The highest weight-loss rate and weight-loss percent were associated with a higher risk of cardiovascular mortality (rate: subdistribution hazard ratio [sHR] 2.27 [95% confidence interval (95% CI) 1.61-3.19]; percent: sHR 2.31 [95% CI 1.06-5.01]) and cancer mortality (rate: sHR 2.36 [95% CI 1.11-5.01]; percent: sHR 1.90 [95% CI 1.00-3.62]). Overweight BMI was protective of cardiovascular mortality (sHR 0.59 [95% CI 0.38-0.91]), while underweight BMI was associated with a near 3-fold increased risk of respiratory mortality (sHR 2.93 [95% CI 1.28-6.67]). Incorporation of time-varying BMI and weight loss in the same models did not substantially alter individual associations for cardiovascular and cancer mortality, but an association between weight-loss percentage and respiratory mortality was attenuated after BMI adjustment. CONCLUSION: Both BMI and weight loss are predictors of cause-specific mortality in RA. Weight loss is a strong predictor of cardiovascular and cancer mortality, while underweight BMI is a stronger predictor of respiratory mortality.
29592999 Treatment of refractory rheumatoid pleural effusion with abatacept. 2018 Mar 28 Rheumatoid pleural effusion is generally responsive to corticosteroids, but refractory cases require consideration of second-line therapy. Here we report the case of a 61-year-old man with rheumatoid arthritis (RA) who developed a large right-sided pleural effusion and was successfully treated with abatacept. Thoracocentesis showed a sterile exudate and an elevated adenosine deaminase level. The methotrexate and etanercept used to treat the RA were withheld initially while he underwent a trial of prednisolone 40 mg/day for the pleural effusion. However, the effusion did not respond to this therapy. Thoracoscopic biopsy of the right pleura revealed fibrotic changes with lymphocyte infiltration mainly composed of CD4(+) T cells and B cells but no evidence of malignancy or infection. The patient was started on abatacept and resumed methotrexate. The treatment was effective in our case. Abatacept should be considered as a treatment option in patients with refractory rheumatoid pleural effusion.
29796841 Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine m 2018 Aug OBJECTIVES: The study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TYMS 2R → 3R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients. METHODS: A total of 185 patients with RA were included. Homocysteine (Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcy > 15 µmol/L. RESULTS: MTHFR C677T polymorphism was associated with HHC in RA patients (multi-adjusted OR, 95% CI 2.18, [1.07-4.57]; p = 0.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTX toxicity (32.7 vs. 16.7%; p = 0.035). CONCLUSIONS: The MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RA patients. HHC could be a useful marker of MTX toxicity in RA patients.
29174791 Patient-perceived health service needs in inflammatory arthritis: A systematic scoping rev 2018 Jun BACKGROUND: Care that is patient-centred is more likely to be sustainable and associated with improved health outcomes. This approach to care requires an understanding of patients' health service needs, yet few studies have directly investigated the perceived health service needs of people with inflammatory arthritis. OBJECTIVES: To systematically identify the existing literature relating to patient perceived health service needs for inflammatory arthritis. METHODS: A systematic review of MEDLINE, EMBASE, CINAHL, and PsycINFO was conducted (1990-2016). Studies examining patients' perceived needs relating to health services for inflammatory arthritis were identified. Descriptive data regarding study design and methodology were extracted and risk of bias assessed. Findings were collated and categorized thematically. RESULTS: In total, 27 of 1405 (16 qualitative, 9 quantitative, and 2 mixed-methods) studies were relevant. The main areas of perceived need related to (1) Communication: consumers wanted clear, empathic communication, and to be involved with decision-making. (2) Characteristics of ongoing care: adequate consultation length with continuity and timely care were valued. (3) Factors influencing care-seeking included individual attitudes, disease severity, finances and family expectations. (4) Allied health and complementary and alternative medicines (CAM) were perceived as useful by many. The reporting of CAM use to doctors was variable, with several factors contributing to under-reporting. CONCLUSIONS: This review identified patients' perceived needs for better communication with their health providers, the heterogeneity of influences determining when care is sought and preferences regarding non-pharmacologic therapies. Aligning patients' perceived needs with evidence-based therapy for people with inflammatory arthritis will be important in optimizing patient outcomes.
30075018 A set of conformationally well-defined L/D-peptide epitopes provides a serological bar cod 2018 Which conformational parameters lead to an antibody-affine peptide antigen? And in how many different conformations can we actually present the respective conformational epitope? To provide answers from a chemical point of view, we direct the bending and tethering of peptide backbones by the utilisation of a hydrophobic cluster, disulfides, and d-amino acids. Each mutation is employed pairwise on directly opposite sides of a β-hairpin. In combination, these synthetic modules guide the formation of complementary β-sheet-like structures, whereby the oppositely configured (l/d-)bi-disulfide pairs form with high regioselectivity. The conformational properties of the peptides are assessed by NMR spectroscopy and correlated with their antibody affinity in ELISA. From a pool of thus designed peptide antigens with distinctive complementary affinities against known rheumatoid arthritis (RA) autoantibodies, we select a set of epitopes for an immunoassay with sera of RA patients. We want to put emphasis on the idea, that the different conformational properties of the chosen antigens, containing the same epitope sequence, are mirrored in the distribution of autoantibody subtypes (or of the antibody polyclonality, respectively). Such directly comparable information can only be delivered by a set of peptides, rather than a single one. The hairpin-restriction technology of l/d-configured bi-disulfide amino acid pairs is not limited to RA but applicable to other shape-persistent hairpin motifs which are supposed to identify subgroups of protein receptors.
29880013 Role of CXCL13 and CCL20 in the recruitment of B cells to inflammatory foci in chronic art 2018 Jun 7 BACKGROUND: B cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors. METHODS: Expression levels of chemokine receptors from the CC and CXC family, as well as CD27, were assessed by flow cytometry in CD20(+) mononuclear cells isolated from the peripheral blood (PB) and synovial fluid (SF) of RA and psoriatic arthritis patients. Transwell experiments were used to study migration of B cells in response to a chemokine or in the presence of multiple chemokines. RESULTS: B cells from the SF of arthritis patients showed a significant increase in the surface expression of CCR1, CCR2, CCR4, CCR5 and CXCR4 with respect to PB. Conversely, SF B cells expressed consistently lower amounts of CXCR5, CXCR7 and CCR6, independent of CD27 expression. Analysis of permeabilized B cells suggested internalization of CXCR5 and CCR6 in SF B cells. In Transwell experiments, CCL20 and CXCL13, ligands of CCR6 and CXCR5, respectively, caused a significantly higher migration of B cells from PB than of those from SF of RA patients. Together, these two chemokines synergistically increased B-cell migration from PB, but not from SF. CONCLUSIONS: These results suggest that CXCL13 and CCL20 might play major roles in RA pathogenesis by acting singly on their selective receptors and synergistically in the accumulation of B cells within the inflamed synovium.
29488292 Patterns of prednisone use during pregnancy in women with rheumatoid arthritis: Daily and 2018 Apr PURPOSE: To characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose, and to evaluate the association between prednisone dose trajectory groups and gestational length. METHODS: This study included pregnant women with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study (2003-2014) before gestational week 20 and reported prednisone use without another oral glucocorticoid during pregnancy (n = 254). Information on medication use and pregnancy outcomes was collected by telephone interview plus by medical record review. Prednisone daily dose and cumulative dose were plotted by gestational day using a heat map for each individual. K-means clustering was used to cluster individual trajectories of prednisone dose into groups. The associations between trajectory group and demographics, disease severity measured by the Health Assessment Questionnaire at enrollment, and gestational length were evaluated. RESULTS: Women used prednisone 3 to 292 days during pregnancy, with daily doses ranging from <1 to 60 mg. Total cumulative dose ranged from 8 to 6225 mg. Disease severity, non-biologic disease modifying anti-rheumatic drug use, and gestational length varied significantly by trajectory group. After adjusting for disease severity, non-biologic disease modifying anti-rheumatic drug use, and other covariates, the highest vs lowest daily dose trajectory group was associated with reduced gestational age at delivery (β: -2.3 weeks (95%: -3.4, -1.3)), as was the highest vs lowest cumulative dose trajectory group (β: -2.6 weeks (95%: -3.6, -1.5)). CONCLUSIONS: In pregnant women with rheumatoid arthritis, patterns of higher prednisone dose were associated with shorter gestational length compared with lower dose.
30236770 NLRP3 inflammasome regulates Th17 differentiation in rheumatoid arthritis. 2018 Dec Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Th17 has been shown to play am important role in the pathogenesis of RA. Accumulating data suggest the involvement of NLRP3 inflammasome in Th17 differentiation in autoimmune diseases. In the current study, we found that NLRP3 inflammasome is activated in CD4 T cells from RA patients. The activation of NLRP3 inflammasome was correlated with disease activities and IL-17A concentration in RA sera. Knockdown of NLRP3 suppressed Th17 differentiation. In addition, caspase-1 or IL-1 receptor inhibitor inhibits Th17 differentiation significantly. Further, ROS production is increased in CD4 T cells from RA patients. The inhibition of ROS production decreased NLRP3 inflammasome activation and IL-1β production in CD4 T cells, leading to the suppression of Th17 differentiation. These findings suggest a pathogenic role of NLRP3 inflammasome in RA by promoting Th17 cell differentiation. NLRP3 inflammasome could be a potential therapeutic target for the treatment of RA.
30232236 Tanshinone IIA promotes the apoptosis of fibroblast-like synoviocytes in rheumatoid arthri 2018 Oct 31 Rheumatoid arthritis (RA) is a common chronic autoimmune joint disease characteristic of elevated proliferation and infiltration of fibroblast-like synoviocytes (FLS). Here, we aimed to explore the mechanisms of the Tanshinone IIA (Tan IIA)-induced apoptosis of FLS from patients with RA (termed RAFLS). Cell Counting Kit-8 (CCK-8) assay and Annexin V staining revealed that RAFLS viability decreased and apoptosis increased after Tan IIA treatment. Long non-coding RNA (lncRNA) GAS5 expression was significantly decreased in the synovial tissues and RAFLS, while Tan IIA treatment resulted in an up-regulation of GAS5. Consistently, knockdown of GAS5 using siRNA inhibited RAFLS apoptosis. Mechanistically, GAS5 knockdown down-regulated the expression of cleaved caspase-3 and caspase-9 in the RAFLS cells and activated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. These data indicate that Tan IIA promotes RAFLS apoptosis by up-regulating lncRNA GAS5, with enhanced expression of cleaved caspase-3/caspase-9 and inhibited PI3K/AKT signaling.
29363647 Elevated Levels of Soluble ST2 were Associated with Rheumatoid Arthritis Disease Activity 2018 Feb 5 BACKGROUND: Much evidence has demonstrated that interleukin (IL)-33 plays an important role in rheumatoid arthritis (RA). However, there have been limited studies about soluble ST2, a receptor for IL-33, in RA. The aims of this study were to detect the levels of ST2 in the serum and synovial fluid of RA patients and to reveal the association of these levels with disease activity and the function of ST2 in RA. METHODS: A total of 56 RA patients and 38 age-matched healthy controls were enrolled in this study. Synovial fluid samples were collected from another 30 RA patients and 20 osteoarthritis patients. Serum and synovial fluid levels of ST2 were measured by ELISA. In addition, the levels of ST2 in the serum of RA patients before and after therapy were detected. The function of ST2 in RA was revealed by the results of an in vitro cell assay, where recombinant ST2 proteins were used to treat peripheral blood mononuclear cells (PBMCs) and RA synovial fibroblasts (RASFs). RESULTS: Serum-soluble ST2 levels were significantly higher in RA patients (127.14 ± 61.43 pg/ml) than those in healthy controls (78.37 ± 41.93 pg/ml, P < 0.01). Synovial fluid-soluble ST2 levels (41.90 ± 33.58 pg/ml) were much higher in RA patients than those in osteoarthritis patients (19.71 ± 16.72 pg/ml, P < 0.05). RA patients who received effective therapy for 6 months showed decreased serum-soluble ST2 levels (113.01 ± 53.90 pg/ml) compared to baseline (139.59 ± 68.36 pg/ml) (P = 0.01). RA patients with high disease activity had higher serum-soluble ST2 levels (162.02 ± 56.78 pg/ml) than those with low disease activity (94.67 ± 40.27 pg/ml, P = 0.001). Soluble ST2 did not affect IL-1β, IL-6, IL-8, or tumor necrosis factor-α (TNF-α) expression in PBMCs from RA patients. However, soluble ST2 ameliorated the expressions of IL-33 and IL-1β but not that of IL-6, IL-8, or TNF-α in resting RASFs. Interestingly, in the RASFs stimulated by TNF-α plus IL-1β, soluble ST2 showed extensive suppressive effects on the expression of IL-6, IL-8, and TNF-α. CONCLUSION: Elevated levels of ST2 in the serum and synovial fluid were associated with disease activity and ameliorated IL-33 expression and IL-33-induced inflammation in RASFs, suggesting that soluble ST2 might be a potential therapeutic candidate for RA.
28941219 Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program. 2018 May OBJECTIVE: Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). We characterized lymphoma events in the tofacitinib RA clinical development program. METHODS: Lymphoma events (up to March 2015) were identified from 19 tofacitinib studies (2 phase I, 9 phase II, 6 phase III, and 2 long-term extension) of patients with moderate to severe RA. Patients in these studies received tofacitinib dosed at 1-30 mg twice daily or 20 mg once daily, as monotherapy or with conventional synthetic disease-modifying antirheumatic drugs. Lymphoma incidence rates (IRs; number of patients with events/100 patient-years) and standardized incidence ratios (SIRs) were calculated. A descriptive case-matched control analysis (1:4) was performed to identify potential risk factors for lymphoma. RESULTS: A total of 6,194 patients received tofacitinib (19,406 patient-years of exposure, 3.4 years median treatment duration). Nineteen lymphomas occurred (IR 0.10 [95% confidence interval (95% CI) 0.06-0.15]), with no increase observed with time of exposure. The age- and sex-adjusted SIR of lymphoma was 2.62 (95% CI 1.58-4.09) (Surveillance, Epidemiology, and End Results [SEER] program database). The clinical characteristics of the 19 lymphomas were typical for the RA population. Three lymphomas were positive for Epstein-Barr virus, 8 were negative, 2 were equivocal, and 6 were untested. Numerically, more lymphoma cases had a history of Sjögren's syndrome and were positive for anti-cyclic citrullinated protein and rheumatoid factor at baseline versus matched controls. The mean corticosteroid dose was higher for lymphoma cases versus controls. CONCLUSION: In the tofacitinib RA clinical development program, lymphoma rates were stable over time and there were minimal differences in the baseline characteristics of patients with and without lymphoma.
30141839 ENHO gene expression and serum adropin level in rheumatoid arthritis and systemic lupus er 2018 Dec BACKGROUND: Adropin, a secreted protein, is encoded by the energy homeostasis-associated gene (ENHO). It is expressed by a variety of tissues and cells. It has been implicated in several physiological and pathological processes, such as angiogenesis and apoptosis. OBJECTIVES: The aim of the present study was to investigate the ENHO gene expression and serum adropin levels in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). MATERIAL AND METHODS: The study included 36 patients with RA, 22 patients with SLE and 20 healthy controls (HC). Patients with a disease activity score-28-erythrocyte sedimentation rate (DAS28-ESR) >2.6 in the RA group and an SLE disease activity index (SLEDAI) >6 in the SLE group were accepted as active. Serum adropin levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) method. The ENHO gene and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expressions in peripheral blood mononuclear cells were analyzed by real-time polymerase chain reaction (PCR). RESULTS: The ENHO gene mRNA expression was significantly higher in the RA group than in the HC group (p = 0.024), although it was similar between the SLE and HC groups (p = 0.920). On the other hand, there were no significant differences among the study groups in terms of serum adropin levels (p > 0.05 for all). Moreover, there was no significant difference in terms of the ENHO expression and serum adropin levels between active and inactive RA and SLE patients. CONCLUSIONS: Although the ENHO gene expression is increased, serum adropin level is not altered in RA. Similarly, adropin seems not to be associated with SLE. However, the potential link between adropin and inflammatory diseases need to be tested by further studies.
29428977 Sleep disorders associated with risk of rheumatoid arthritis. 2018 Dec BACKGROUND: Immune disorders impair sleep quality and sleep disorders (SDs) may derange immune function. PURPOSE: The study evaluated the incidence and risk of rheumatoid arthritis (RA) in patients with SDs using a nationwide cohort. METHODS: We recognized the patients with SDs from 1998 to 2002 by using the Taiwan National Health Insurance Research Database. One control patient for each SD patient was randomly selected and matched based on the proportion of age, sex, and index year. We calculated the person years of follow-up for each participant from the index date to RA diagnosis, censoring, or until December 31, 2011. The risk of RA was estimated by using Cox models incorporating demographics and comorbidities. RESULTS: We enrolled 65,754 patients with SDs and 65,753 controls and followed for 637,906 and 662,514 person-years, respectively. The patients with SDs exhibited a 1.49-fold greater risk of RA development compared with the comparison cohort when we adjusted for covariates. The patients with sleep apnea (SA) showed the greatest incidence density rate of RA, followed by those with non-apnea SDs and the non-SD cohort (4.11, 3.29, and 2.15 per 10,000 person-years, respectively). The SA cohort had a 2.56-fold adjusted hazard ratio (aHR) of RA (95% confidence interval [CI] = 1.11-5.91) and the non-apnea SD cohort had a 1.47-fold aHR of RA (95% CI = 1.18-1.84) compared with the non-SD cohort. Women with SDs presented a considerable risk of developing RA. CONCLUSIONS: This nationwide cohort study indicates that SDs are associated with the risk of RA development.
29486306 Altered levels of exhaled nitric oxide in rheumatoid arthritis. 2018 Jun 1 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by bone and joint destruction, but other organ systems can also be involved. Recent studies have suggested that the disease may start in the lungs. Exhaled nitric oxide (F(E)NO) is a marker of inflammation. The aims of the study were to compare the NO parameters between subjects with RA and healthy control subjects, and to examine whether the NO parameters correlated with lung function and disease activity in the subjects with RA. METHODS: Subjects with RA (n = 35) were recruited during their regular outpatient visits to the rheumatology department. The nitric oxide (NO) parameters: alveolar NO concentration (C(A)NO), airway compartment diffusing capacity of NO (D(aw)NO), and tissue concentration of NO in the airway wall (C(aw)NO), were algorithmically estimated. Healthy subjects (n = 35) matched by age, gender and height were used as controls. Data are given in median, (quartile 25, 75). Wilcoxon Matched Pairs test was used for group comparisons. Mann-Whitney U test was used to make comparisons between any two groups and for pairwise comparisons. Correlations were tested with Spearman rank order correlation. RESULTS: C(A)NO was significantly lower in the RA subjects compared with healthy subjects; 1.1 (0.5, 1.8) ppb versus 2.4 (2.0, 3.0) ppb, (p < 0.001). C(aw)NO was significantly lower in the RA subjects with 51 (22, 87) ppb versus 120 (76, 162) ppb in the control group. D(aw)NO was significantly higher at 25 (15, 36) mL/s in the RA group versus the control group's 7.7 (5.3, 10.7) mL/s. CONCLUSIONS: There are significant differences between subjects with RA and matched healthy control subjects regarding the exhaled NO parameters. It is unclear if this can be explained by the pathogenesis of RA, consequences of long-term disease, and/or due to drug treatment.
29891493 The impact of low-dose glucocorticoids on disease activity, bone mineral density, fragilit 2018 Aug This study aimed to investigate the effect of low-dose glucocorticoids (LDGs) on disease activity, bone density, and fractures in patients with rheumatoid arthritis (RA). This was an interim analysis of the RA Registry. Demographic data and clinical characteristics, including fracture risk assessment tool, were collected. 25(OH) Vitamin D, bone mineral density (BMD), and intact parathyroid hormone were measured at enrollment. The study group were those who took LDGs (2.5-7.5 mg/day prednisolone or equivalent dose), and the others were included as the control group. A total of 425 participants were enrolled, including 85 (20%) in the control group and 340 (80%) in the study group. The demographics and clinical characteristics were comparable between the two groups. Compared with the control group, the LDGs group had a significantly lower vertebral BMD (L 1-4) (g/cm(2)), (0.854 vs 0.896, p=0.046), significantly higher rate of previous fractures (103 (30.3%) vs 13 (15.3%), p=0.006), higher 10-year probability of major fractures (14 (15.5) vs 8 (8.6), p<0.0001), and higher 10-year probability of hip fractures (4.4 (8.4) vs 2 (3.9), p<0.0001). Disease activity appeared to be similar in the patients with RA regardless of whether or not they received LDG treatment. However, the patients with RA who received LDG treatment had a lower BMD at the spine (L1-4) and a higher rate of previous fractures that was associated with a significantly higher 10-year probability of fractures than those who did not receive LDG treatment.