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ID PMID Title PublicationDate abstract
28293776 Long-term outcomes of treat-to-target strategy in established rheumatoid arthritis: a dail 2017 Jun To examine disease activity and physical function after implementation of treat-to-target (T2T) strategy in patients with established rheumatoid arthritis (RA) over a long-term period. Patients with RA were started on a T2T strategy in 2005 and followed through 2014. Patients were seen every 3-4 months until remission/low disease activity was achieved and every 6 months thereafter. Disease activity was measured by the DAS28 and CDAI, and physical function by the HAQ-DI. Results were presented as all observed data, without imputation for missing values. Changes in disease activity and physical function were evaluated by generalized estimating equations (GEE). Two hundred and twenty-nine patients were included, with a mean (SD) disease duration of 10.6 (7.4) years. Significant improvements were seen in both composite scores during the follow-up period, as demonstrated by DAS28 (β coefficient = 0.19; 95% CI = 0.16-0.21; p < 0.01) and by CDAI (β coefficient = 1.59; 95% CI = 1.84-1.34; p < 0.01). Physical function also improved, as demonstrated by HAQ-DI (β coefficient = 0.03; 95% CI = 0.02-0.04; p < 0.01). Biological therapy was associated with improvement in disease activity and in physical function. Leflunomide was only associated with improvement in physical function. Clinically meaningful reductions of DAS28, CDAI and HAQ-DI were observed in patients with established rheumatoid arthritis from 2005 to 2014. Implementation of new therapeutic options, in the scenario of T2T strategy, was associated with improvement in disease activity and physical function.
28124095 Pain, social support and depressive symptoms in patients with rheumatoid arthritis: testin 2017 Jun This study investigated as to how social support influences health among people with rheumatoid arthritis (RA). We refer to the stress-buffering hypothesis of social support which suggests that the negative consequences of stressors on health outcomes can be buffered by social support. In this study, pain represents a stressor and depressive symptoms represent negative health outcomes. It was hypothesized that higher levels of social support should attenuate the association between pain and depression in RA. A cross-sectional study was conducted in 361 patients with RA. They completed questionnaires on social support, depression and perceived pain. Linear regression analysis was applied, with pain as the main explanatory variable, depression as a dependent variable, and an interaction term "social support × pain". Both pain and social support showed significant associations with depression, with more severe pain and lower social support going along with a higher depression score. However, the interaction term "social support × pain" was not significant, indicating that social support did not attenuate the association between pain and depression. Social support was inversely associated with the experience of depressive symptoms among people suffering from RA. However, it had no buffering effect in attenuating the postulated association between the stressor "pain" and the negative health outcomes assessed as depressive symptoms. The stress-buffering hypothesis of social support was not supported by data from this study among people suffering from RA.
27416107 Whole genome analysis on the genetic backgrounds associated with the secondary failure to 2017 Mar OBJECTIVES: Etanercept is effective for the treatment of rheumatoid arthritis (RA). However, some of the patients eventually lose efficacy (secondary failure) despite the absence of neutralizing antibodies. We aimed to explore single nucleotide polymorphisms (SNPs) associated with secondary failure. METHODS: We recruited RA patients given etanercept at 50 mg/week for ≥6 months from the Matsubara Mayflower Hospital RA registry. They were assigned to responders, secondary failure patients, and non-responders according to Disease Activity Score. Genome-wide association study (GWAS) was performed using Illumina HumanHAP300k BeadChips and the results were analyzed with Plink software. Clinical backgrounds were compared by ANOVA and contingency table analysis. The protocol was approved by IRB and written informed consent was obtained. RESULTS: Ninety, 27 and 17 patients were assigned to responders, secondary failure patients, and non-responders, respectively. No significant differences were observed regarding clinical backgrounds among the groups. GWAS revealed that six and 37 SNPs may be associated with secondary failure to etanercept with p< 10(-6) and <10(-5), respectively. CONCLUSION: While our preliminary results with borderline significance should be validated by studies with a greater population size, some of the SNPs detected by our GWAS may be involved in the development of secondary failure to etanercept.
28386080 Differential activation of endocrine-immune networks by arthritis challenge: Insights from 2017 Apr 6 Rheumatoid arthritis (RA) is a chronic inflammatory condition with variable clinical presentation and disease progression. Importantly, animal models of RA are widely used to examine disease pathophysiology/treatments. Here, we exploited known vendor colony-based differences in endocrine/immune responses to gain insight into inflammatory modulators in arthritis, utilizing the adjuvant-induced arthritis (AA) model. Our previous study found that Sprague-Dawley (SD) rats from Harlan develop more severe AA, have lower corticosteroid binding globulin, and have different patterns of cytokine activation in the hind paw, compared to SD rats from Charles River. Here, we extend these findings, demonstrating that Harlan rats show reduced hypothalamic cytokine responses to AA, compared to Charles River rats, and identify colony-based differences in cytokine profiles in hippocampus and spleen. To go beyond individual measures, probing for networks of variables underlying differential responses, we combined datasets from this and the previous study and performed constrained principal component analysis (CPCA). CPCA revealed that with AA, Charles River rats show activation of chemokine and central cytokine networks, whereas Harlan rats activate peripheral immune/hypothalamic-pituitary-adrenal networks. These data suggest differential underlying disease mechanism(s), highlighting the power of evaluating multiple disease biomarkers, with potential implications for understanding differential disease profiles in individuals with RA.
28778350 Econometric modelling of multiple self-reports of health states: The switch from EQ-5D-3L 2017 Sep EQ-5D is used in cost-effectiveness studies underlying many important health policy decisions. It comprises a survey instrument describing health states across five domains, and a system of utility values for each state. The original 3-level version of EQ-5D is being replaced with a more sensitive 5-level version but the consequences of this change are uncertain. We develop a multi-equation ordinal response model incorporating a copula specification with normal mixture marginals to analyse joint responses to EQ-5D-3L and EQ-5D-5L in a survey of people with rheumatic disease, and use it to generate mappings between the alternative descriptive systems. We revisit a major cost-effectiveness study of drug therapies for rheumatoid arthritis, mapping the original EQ-5D-3L measure onto a 5L valuation basis. Working within a comprehensive, flexible econometric framework, we find that use of simpler restricted specifications can make very large changes to cost-effectiveness estimates with serious implications for decision-making.
27863147 Physical Activity and Correlates of Physical Activity Participation Over Three Years in Ad 2017 Oct OBJECTIVE: To characterize physical activity participation (moderate-to-vigorous physical activity [MVPA], ≥150 minutes of moderate physical activity or 75 minutes of vigorous physical activity per week), to examine associations between disease activity and MVPA, and to identify MVPA correlates in adults with rheumatoid arthritis (RA) over 3 years. METHODS: This study included 573 RA patients (94% white, 83% female, mean age 61 years, mean RA duration 19.5 years) with ≥1 annual registry visit and who completed the physical activity questionnaire. Baseline and annual measures included demographics/medical history, self-efficacy for disease management, quality of life, patient/physician global assessment, physical function, and self-reported physical activity. A logistic repeated-measures model using the generalized estimating equation examined the relationship between disease activity and MVPA. RESULTS: Average disease activity (from the 3-variable Disease Activity Score in 28 joints using the C-reactive protein level) was mean ± SD 3.1 ± 1.4, 36% were physically inactive, and 29% met MVPA recommendations. There was a negative borderline association with disease activity (odds ratio [OR] 0.89 [95% confidence interval (95% CI) 0.79-1.00]). Correlates of meeting MVPA recommendations, adjusting for disease activity, were being white (OR 2.95 [95% CI 1.29-6.75]), older age (ages >69 years OR 0.58 [95% CI 0.36-0.92]), poor mental health (OR 0.63 [95% CI 0.41-0.95]), poor physical function (OR 0.59 [95% CI 0.34-1.01]), overweight/obese (body mass index [BMI] >25-30 OR 0.69 [95% CI 0.50-0.95], BMI >30-39.9 OR 0.60 [95% CI 0.41-0.88], and BMI ≤40 OR 0.24 [95% CI 0.08-0.74]), and patient global assessment (≥10-20 OR 0.57 [95% CI 0.39-0.83]). CONCLUSION: A small proportion of patients met MVPA recommendations despite well-controlled disease. Disease activity was negatively associated with physical activity over time. Physical activity correlates were linked to lifestyle, mental health, and patient perceptions of disease, suggesting physical activity interventions that address patient perspectives may facilitate RA management.
28912189 Associations between circulating macrophage migration inhibitory factor (MIF) levels and r 2018 Feb AIM: To systematically review evidence regarding the relationship between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis (RA), and the association between MIF gene polymorphisms and RA susceptibility. DESIGN: We performed a meta-analysis on data of serum/plasma MIF levels in patients with RA and in controls, and on associations between the MIF-173 C/G and -794CATT(5-8) polymorphisms and RA susceptibility. PATIENTS: Twelve studies, comprising a total of 362 RA cases and 531 controls evaluated for MIF levels, and 2367 RA cases and 2395 controls evaluated for MIF polymorphisms, were included. RESULTS: MIF levels were significantly higher in the RA group than in the control group (standardised mean difference (95% CI) 0.923 (0.766 to 1.080), p<0.001). Stratification by ethnicity revealed significantly higher MIF levels in the RA group in Caucasian, Asian and Latin American populations. MIF levels were significantly higher in patients with RA, regardless of adjustment, sample size or data type evaluated. RA was identified to be significantly associated with the MIF-173 C allele (OR (95% CI) 1.271 (1.141 to 1.416), p<0.001), as well as with the -794CATT(7) allele (OR (95% CI) 1.229 (1.084 to 1.415), p=0.002) and the -794CATT(7)-MIF-173C haplotype RA (OR (95% CI) 1.433 (1.138 to 1.805), p=0.002). CONCLUSIONS: Our meta-analyses revealed significantly higher circulating MIF levels in patients with RA, and found evidence of associations between the MIF-173 C/G and -794CATT(5-8) polymorphisms and RA susceptibility.
28002154 The Role of 25-Hydroxyvitamin D as a Predictor of Clinical and Radiological Outcomes in Ea 2017 Jan OBJECTIVE: The aims of this study were to compare the levels of 25-hydroxyvitamin D (25(OH)D) in patients with early-onset rheumatoid arthritis (EORA) versus a healthy control group and to assess the association of 25(OH)D deficiency and the BsmI polymorphism of the vitamin D receptor gene with clinical, radiological, and laboratory parameters. METHODS: Early-onset RA Colombian patients were enrolled in a 3-year follow-up study. Vitamin D deficiency was diagnosed for 25(OH)D levels of less than 20 ng/mL. Pearson and Spearman correlation coefficients were used to assess data. RESULTS: Seventy patients and 70 matched healthy subjects were included. 25-Hydroxyvitamin D was lower in the EORA group (27.13 [SD, 13.4] ng/mL vs. 33.74 [SD, 16.7] ng/mL; P = 0.01); 31.4% of EORA patients were vitamin D deficient. Remission was higher in subjects without 25(OH)D deficiency (22.7% vs. 47.9%; P = 0.04). Patients with 25(OH)D deficiency at baseline had higher Health Assessment Questionnaire and Physician Global Disease Activity Assessment scores, fatigue levels, erythrocyte sedimentation rate, and morning stiffness after 3 years. At disease onset, only a relationship between 25(OH)D deficiency with fatigue and morning stiffness was found. Neither radiographic progression nor Sharp van der-Heidje score was associated to hypovitaminosis D after 36-month follow-up. The bb genotype was less frequent in patients with vitamin D deficiency (0% vs. 16.6%; P = 0.04). Patients with BB-Bb genotype had lower 25(OH)D and a propensity to more severe disease. CONCLUSIONS: Our data provide further support for a role of vitamin D as a clinical biomarker for RA. Baseline 25(OH)D could have potential as a predictor of disease severity in EORA.
27919200 Bony ankylosis of the facet joint of the cervical spine in rheumatoid arthritis: Its chara 2017 Sep OBJECTIVES: The purpose of this study was to clarify the characteristics of bony ankylosis of the facet joint of the cervical spine in rheumatoid arthritis (RA) patients who required cervical spine surgery, and its relationship to the clinical findings. METHODS: Eighty consecutive RA patients with cervical spine disorder who received initial surgery were reviewed. The occurrence of bony ankylosis of the facet joint of the cervical spine was investigated using computed tomography (CT) before surgery. We also evaluated the severity of neurological symptoms and the plain wrist radiographs taken before surgery; furthermore, we evaluated each patient's medical history for total knee arthroplasty (TKA) or hip arthroplasty (THA). RESULTS: The preoperative CT imaging demonstrated bony ankylosis of the facet joint of the cervical spine in 45 facet levels of 19 cases (BA + group). In all patients, responsible instability or stenosis was demonstrated just caudal or on the cranial side of those bony ankylosis. Before surgery, the BA + group included significantly more patients showing severe cervical myelopathy (p < 0.05), and significantly more cases showing progressed ankylosis in the wrist joint bilaterally (p < 0.01). There were also significantly more patients who received two or more TKA or THA before the cervical spine surgery in the BA + group (p < 0.01). CONCLUSIONS: Bony ankylosis of the facet joint of the cervical spine may be a risk factor of instability or stenosis at the adjacent disc level and severe cervical myelopathy. Furthermore, its ankylosis was demonstrated in RA patients with severe destroyed joints.
28706330 Effects of co-treatment with pioglitazone and methotrexate on experimentally induced rheum 2017 Mar OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting the synovial joints of the body. Methotrexate (MTX) is considered as a mainstay in the management of RA. However, monotherapy with MTX in RA is often limited by potential long-term toxicity. The present study was conducted to evaluate if MTX-pioglitazone combination therapy has an add-on benefit over monotherapy with MTX or pioglitazone on disease activity in male Wistar rats in adjuvant-induced arthritis model. MATERIALS AND METHODS: Arthritis was induced by single subcutaneous injection of complete Freund's adjuvant (CFA) in thirty male Wistar albino rats. They were then divided into five equal groups, which included two control groups (arthritic and nonarthritic), pioglitazone-treated (1.35 mg/kg daily), MTX-treated (0.225 mg/kg daily), and MTX + pioglitazone-treated. The disease-modifying action of the drugs was assessed by various physiological, hematological, and biochemical parameters along with histopathological and radiological analysis of affected joints. The experimental data were statistically assessed by one-way ANOVA. RESULTS: There was a significant reduction of disease activity in the MTX monotherapy group when compared with disease control. However, pioglitazone monotherapy group failed to demonstrate any significant effect on disease activity. The MTX-pioglitazone combination group demonstrated greater suppression of disease activity as compared to MTX and pioglitazone monotherapy and disease control group (P < 0.05). CONCLUSION: The present study demonstrates that the combination therapy of MTX with pioglitazone offers better control of disease activities in RA as compared to MTX or pioglitazone monotherapy.
28449692 Clinical and demographic factors associated with change and maintenance of disease severit 2017 Apr 27 BACKGROUND: We examined models to predict disease activity transitions from moderate to low or severe and associated factors in patients with rheumatoid arthritis (RA). METHODS: Data from RA patients enrolled in the Corrona registry (October 2001 to August 2014) were analyzed. Clinical Disease Activity Index (CDAI) definitions were used for low (≤10), moderate (>10 and ≤22), and severe (>22) disease activity states. A Markov model for repeated measures allowing for covariate dependence was used to model transitions between three (low, moderate, severe) states and estimate population transition probabilities. Mean sojourn times were calculated to compare length of time in particular states. Logistic regression models were used to examine impacts of covariates (time between visits, chronological year, disease duration, age) on disease states. RESULTS: Data from 29,853 patients (251,375 visits) and a sub-cohort of 9812 patients (46,534 visits) with regular visits (every 3-9 months) were analyzed. The probability of moving from moderate to low or severe disease by next visit was 47% and 18%, respectively. Patients stayed in moderate disease for mean 4.25 months (95% confidence interval: 4.18-4.32). Transition probabilities showed 20% of patients with low disease activity moved to moderate or severe disease within 6 months; >35% of patients with moderate disease remained in moderate disease after 6 months. Results were similar for the regular-visit sub-cohort. Significant interactions with prior disease state were seen with chronological year and disease duration. CONCLUSION: A substantial proportion of patients remain in moderate disease, emphasizing the need for treat-to-target strategies for RA patients.
28608433 Performances of Clinical Disease Activity Index (CDAI) and Simplified Disease Activity In 2018 Nov BACKGROUND/PURPOSE: To compare the performance of Disease Assessment Score of 28 joints - C-reactive protein (DAS-28-CRP), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) composite measures to assess status of patients with rheumatoid arthritis (RA) on methotrexate, versus DAS-28 CRP as the gold standard. METHODS: One hundred and thirty-five patients with RA as per the 2010 American College of Rheumatology/European League Against Rheumatism criteria were included in the prospective study. The disease activity was assessed at baseline and at every 6 weeks for 24 weeks, by DAS-28-CRP, CDAI and SDAI. Patients were divided into groups of remission, low, moderate and high activity on the basis of predefined cut-offs for DAS-28-CRP, CDAI and SDAI. A Spearman correlation between composite measures and inter-group comparison of the measures was performed. RESULTS: There was an excellent positive correlation between DAS-28-CRP and CDAI (linear weighted κ baseline - 0.545), DAS-28 CRP and SDAI (linear weighted κ - 0.689) at baseline. There was moderate agreement between DAS-28-CRP and CDAI (linear weighted κ final visit - 0.458) at final visit. There was moderate correlation between SDAI and DAS-28-CRP at final visit (linear weighted κ - 0.470). However, correlation between CDAI versus SDAI remained excellent at baseline and final visit. Patients in remission as per DAS-28-CRP had significantly more residual disease activity compared to SDAI and CDAI remission criteria. CONCLUSION: The study shows an excellent strong positive correlation between DAS-28-CRP, CDAI and SDAI at initial evaluation but not at final visit. SDAI- and CDAI-based remission criteria seem to be better than DAS-28-CRP-based remission criteria.
26929002 Psychometric validation of Chinese Health Assessment Questionnaire for use in rheumatoid a 2017 Dec BACKGROUND: To validate the psychometric properties of the Chinese Health Assessment Questionnaire (HAQ) for use in rheumatoid arthritis (RA) patients in China. METHODS: The psychometric properties of the HAQ were validated by interviewing subjects with a questionnaire battery containing the HAQ, EQ-5D, and Short Form 12 (SF-12). Reliability was assessed by Cronbach's alpha, construct validity by assessing a priori hypotheses, and discriminative validity by discriminating subjects in different groups, respectively. To assess the applicability of HAQ in different regions, subgroup analyses were conducted for south and north China, respectively. RESULTS: Questionnaires were administered to a consecutive sample of 133 RA patients. Cronbach's alpha showed a strong reliability among all the items. In particular, the internal reliability was higher when excluding the items about the use of aids and devices: 0.987 when excluding versus 0.963 when including. Construct validity was supported by achieving both of the a priori hypotheses based on correlations between the HAQ scores and scales of EQ-5D and SF-12. Overall, HAQ scores were important inferential factors for Global Functional Status in RA, which indicated good discriminative validity. The validation results are generally consistent between subgroups from north and south China. CONCLUSIONS: The Chinese HAQ demonstrated good acceptability and psychometric properties in RA patients from China. Two possible improvements for better use and interpretation of the patient-reported outcomes of RA patients in China could be to cross-culturally adapt the items about the use of aids and devices and joint use of mental health measurements together with HAQ in future studies.
28205333 Longitudinal study of clinical prognostic factors in patients with early rheumatoid arthri 2017 Apr AIM: To assess the association between baseline clinical prognostic factors and subsequent Disease Activity Score of 28 joints (DAS28) remission in early rheumatoid arthritis (RA). METHODS: Data were collected using point of care clinical software from participating rheumatology centres. Patients aged 18 years or over whose date of clinical onset of RA was within the previous 12-24 months, who had at least 6 months of follow-up data and a DAS28-ESR (erythrocyte sedimentation rate) score recorded between 12 and 24 months from first being seen for RA were included. Data collected included baseline demographics, mode of disease onset, pattern of joint involvement at onset, smoking status, DAS28, rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), time from symptom onset to presentation and disease activity at baseline. Univariate and multivariate logistic regression of DAS28-ESR remission between 12 and 24 months after first assessment were performed. RESULTS: Data from 1017 patients were analyzed: 70% female; mean age 60 years (SD: 14.7); 70% RF-positive, 58% ACPA-positive. The strongest age and sex adjusted baseline predictors of DAS28-ESR remission at 12-24 months were remission at baseline (odds ratio [OR]: 4.49, 95% CI: 2.17-9.29, P < 0.001), being male (OR: 2.42, 95% CI: 1.46-4.01, P < 0.001), abstaining from alcohol (P < 0.001) and being lower weight (OR: 0.98, 95% CI: 0.97-1.00, P = 0.015). There was no statistically significant association between joint onset patterns, mode of onset, RF, ACPA or smoking status. CONCLUSION: In this observational study, patients with early RA at risk of not achieving remission include those with high disease activity at baseline, women, those who drink alcohol and those with higher body weight.
28340006 Benefit of biologics initiation in moderate versus severe rheumatoid arthritis: evidence f 2017 Jul 1 OBJECTIVES: To compare clinical outcomes and treatment patterns among patients with moderate vs severe RA following biologic DMARD initiation. METHODS: Biologics-naive patients with moderate to severe RA [Clinical Disease Activity Index (CDAI) >10] who initiated a biologic DMARD were selected from the Corrona registry (2001-13). CDAI, functional status [modified HAQ (mHAQ)] and patterns of drug use were compared at 1 and 2 years post-initiation between patients with moderate (CDAI >10⩽22) vs severe (CDAI >22) baseline disease activity. RESULTS: A total of 1596 patients (817 severe, 779 moderate) had ⩾1 year of follow-up and 1269 (635 severe, 634 moderate) had ⩾2 years of follow-up. Patients with severe vs moderate baseline disease activity experienced greater improvements in disease activity [mean change in CDAI -18.9 vs -6.0 at year 1; -21.0 vs -7.1 at year 2 ( P < 0.0001)] and physical function [mean change in mHAQ -0.2 vs -0.1 ( P < 0.0001) at year 1; -0.2 vs -0.1 ( P = 0.0013) at year 2]. Greater proportions of patients with moderate vs severe disease activity achieved remission (CDAI ⩽2.8) [22.7 vs 15.8% ( P = 0.0003) at year 1; 25.9 vs 20.9% ( P = 0.0396) at year 2] or low disease activity (CDAI <10) [60.1 vs 41.2% at year 1; 66.7 vs 49.4% at year 2 ( P < 0.0001)]. Most patients remained on the original biologic drug (>70% at year 1; >62% at year 2). CONCLUSION: With biologic therapy, RA patients with higher baseline disease activity achieved greater improvements in measures of disease activity than those with lower levels of disease, but less often achieved the common targets of remission or low disease activity.
27273981 Direct and Indirect Determinants of the Patient Global Assessment in Rheumatoid Arthritis: 2017 Mar OBJECTIVE: In rheumatoid arthritis (RA), the patient global assessment (PGA) has been strongly associated with pain severity, but less often with other measures, including disease activity measures. We tested whether RA activity and psychological measures had direct associations with the PGA or indirect associations that were mediated by pain. We also tested whether the correlates of the PGA differed with the degree of RA activity. METHODS: We studied 260 patients with active RA on 2 visits in a prospective longitudinal study. We used path analysis to test direct and indirect associations of Disease Activity Score in 28 joints (DAS28), morning stiffness, Health Assessment Questionnaire (HAQ), fatigue, physical role limitations, social functioning, depressive symptoms, and health distress with the PGA. RESULTS: Among the 509 visits, the median PGA score was 50 (25th-75th percentile: 24-66). Pain severity had the strongest association with the PGA, but direct associations were also found for morning stiffness severity, health distress, fatigue, and DAS28. Morning stiffness severity, DAS28, health distress, and HAQ were also indirectly associated with the PGA through pain. Among visits with DAS28 ≥5.4, pain, morning stiffness severity, and HAQ were the only determinants of the PGA. Among visits with DAS28 <4.2, health distress and age were additional determinants, and fatigue was marginally associated with the PGA. CONCLUSION: Although pain was the strongest determinant of the PGA in RA, morning stiffness severity, health distress, fatigue, and DAS28 were also important. Determinants of the PGA differed with RA activity, with health distress, age, and to a lesser degree, fatigue, contributing only in patients with less active RA.
28366675 The dual regulation of substance P-mediated inflammation via human synovial mast cells in 2017 Sep BACKGROUND: Neural pathways are thought to be directly involved in the pathogenesis of rheumatoid arthritis (RA). Although synovial mast cells (MCs) are activated by substance P (SP), the role of MCs in neural pathways in RA remains unknown. The aims of this study were to investigate 1) whether tachykinins are produced by synovial MCs and whether production differs in RA and osteoarthritis (OA) patients, and 2) what is the responsible receptor for SP in synovial MCs. METHODS: Synovial tissues were obtained from patients with RA or OA undergoing joint replacement surgery. Cultured synovium-derived MCs were generated by culturing dispersed synovial cells with stem cell factor. SP expression was investigated using immunofluorescence and enzyme immunoassays. Mas-related gene X2 (MrgX2) expression was reduced in human MCs using a lentiviral shRNA silencing technique. RESULTS: SP expression was localized around the cell membrane in 41% (median) of the MCs in synovium from RA but in only 7% of that from OA, suggesting the activation of MCs. Synovial MCs expressed tachykinin (TAC) 1 mRNA, the expression of which was upregulated by the aggregation of FcɛRI or the addition of aggregated IgG. However, the released SP appeared to be rapidly degraded by MC chymase. Synovial MCs were activated with SP through MrgX2 to release histamine without producing proinflammatory cytokines. CONCLUSIONS: Activated synovial MCs may rapidly degrade SP, which may downregulate the SP-mediated activation of synoviocytes in RA. On the other hand, SP activates MCs to induce inflammatory mediators, suggesting the dual regulation of SP-mediated inflammation by MCs in RA.
29173692 Socioeconomic and therapy factor influence on self-reported fatigue, anxiety and depressio 2017 Nov INTRODUCTION: Fatigue, anxiety and depression are very frequent symptoms in patients with rheumatoid arthritis (RA). GOALS: In this study we evaluated the influence of socioeconomic characteristics, therapy and comorbidities on the self-reported high fatigue, anxiety and depression in patients with RA. METHOD: Multicenter cross-sectional study was performed in 22 health institutions in Serbia during the period from April-August 2014 in population of older RA patients. Self-reported patients health status was measured by: Fatigue Assessment Scale, Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Treatment modalities were defined as: (1) non-steroidal anti-inflammatory drugs (NSAIDs) and/or analgesics and/or corticosteroids; (2) synthetic disease-modifying antirheumatic drugs (DMARDs) alone or in combination with corticosteroids and/or NSAIDs and (3) any RA treatment which includes biologic DMARDs. RESULTS: There were significant predictors of high depression: synthetic DMARDs therapy in combination with corticosteroids and/or NSAIDs, physiotherapist self-payment, frequent taxi use, alternative treatment and employment status. The need for another person's assistance, supplemental calcium therapy and professional qualifications were the predictors of a high fatigue, whereas the age above 65 years had the protective effect on it. Anxiety was an independent high fatigue predictor. The predictors of a high anxiety were: gastroprotection with proton-pump inhibitors and patient occupation. CONCLUSION: Socioeconomic predictors of self-reported high depression, anxiety or fatigue are different for each of the mentioned outcomes, while accompanied with the basic RA treatment they exclusively explain a high depression. The anxiety, jointed with the socioeconomic variables and supplemental therapy, is a significant fatigue predictor in RA patients.
27909795 Altered gut microbiota in RA: implications for treatment. 2017 Jun Rheumatoid arthritis (RA) is an autoimmune disease with progressive joint disorder. The complex interplay of genetic and environmental influences is important for the development of the disease. A growing body of evidence has shed light on the association of dysbiosis of gut microbiota with RA. Certain gut microbial strains have been shown to inhibit or attenuate immune responses in RA experimental models, suggesting that specific species among intestinal commensal bacteria may play either a pathogenic or a protective role in the development of RA. Oral intake of probiotics/prebiotics can therefore represent a therapeutic approach for RA treatment. However, the relevant scientific work has only just begun, and the available data in this field remain limited. Fortunately, utilization of new sequencing technologies allows expanded research on the association of intestinal bacterial flora and human diseases to be attempted. In this review, we summarize the role of gut microbiota in RA progression and address how specific bacterial strains regulate the immune response in disease process. Probiotics/prebiotics in the treatment of RA is also discussed.
24716863 Risk factors of adverse events during treatment in elderly patients with rheumatoid arthri 2017 Mar OBJECTIVES: The risk factors of adverse events during a number of currently used treatments for rheumatoid arthritis (RA) in elderly patients were examined. METHODS: A retrospective observational study was conducted for 300 elderly RA patients registered in December 2009 at Sasebo Chuo Hospital, Japan, and the adverse events during the treatments for RA were assessed. RESULTS: The average age of the patients was 74.3 ± 5.8 years. The Steinbrocker stage was IV in almost one-half of the patients. Methotrexate (MTX) was used in 54.0% of patients and biologics in 23.0% of patients. Adverse events occurred in 103 patients (34.3%). The most common adverse events were infections (46.6%), including pneumonia (21.4%). Multiple logistic analyses revealed that the factors significantly related to infection were advanced Steinbrocker stage and the existence of respiratory diseases, and that of pneumonia was the existence of diabetes mellitus (DM). CONCLUSIONS: The elderly RA patients with advanced stage, respiratory diseases or DM should be monitored for infections, including pneumonia, carefully during treatment.