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ID PMID Title PublicationDate abstract
30979397 Comparative safety of abatacept in rheumatoid arthritis with COPD: A real-world population 2019 Dec OBJECTIVE: The ASSURE randomized trial of abatacept safety in rheumatoid arthritis (RA) reported more frequent respiratory adverse events with abatacept among the subgroup of 54 patients with chronic obstructive pulmonary disease (COPD), leading to a label warning. We assessed the risk of adverse respiratory events associated with abatacept, compared with other biologic DMARDs (bDMARDs), among patients with RA and COPD in a real-world observational setting. METHODS: We formed a prevalent new-user cohort of patients with RA and COPD treated with bDMARDs within the US-based MarketScan databases from 2007 to 2014. Abatacept users were matched on time-conditional propensity scores to users of other bDMARDs. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of adverse respiratory events comparing abatacept with other bDMARDs were estimated using the Cox model. RESULTS: The cohort included 1807 patients initiating abatacept and 3547 matched patients initiating another bDMARD. The HR of the combined endpoint of hospitalized COPD exacerbation, bronchitis and hospitalized pneumonia or influenza with abatacept relative to other bDMARDs was 0.87 (95% CI: 0.68-1.12). For hospitalized COPD exacerbation it was 0.60 (95% CI: 0.32-1.11), 0.80 (95% CI: 0.56-1.14) for bronchitis, while for pneumonia or influenza it was 1.39 (95% CI: 0.91-2.13) if hospitalized and 1.05 (95% CI: 0.86-1.29) as outpatient. CONCLUSION: This large safety study from a real world setting finds no increased risk of adverse respiratory events with abatacept compared with other bDMARDs in patients with RA and COPD. This study does not substantiate the safety signal raised by the smaller ASSURE trial.
31327051 Moderate-to-high intensity exercise with person-centered guidance influences fatigue in ol 2019 Sep Fatigue is described as a dominant and disturbing symptom of rheumatoid arthritis (RA) regardless of the advances in pharmacological treatment. Fatigue is also found to correlate with depression. The objective was to evaluate the impact of moderate-to-high intensity, aerobic and resistance exercise with person-centered guidance on fatigue, anxiety and depression, in older adults with RA. Comparisons were made between older adults (> 65 years) with RA taking part in a 20-week moderate-to-high intensity exercise at a gym (n = 36) or in home-based exercise of light intensity (n = 38). Assessments were performed at baseline, at 20 weeks, and at 52 weeks. Outcomes were differences in Multidimensional Fatigue Inventory (MFI-20), Visual Analog Scale Fatigue (VAS fatigue), and Hospital Anxiety and Depression Scale (HADS). Analysis of metabolomics was also performed. The subscales "physical fatigue" and "mental fatigue" in MFI-20 and symptoms of depression using HADS depression scale improved significantly at week 20 in the exercise group compared with the control group. Exercise did not influence global fatigue rated by VAS or subscales "reduced motivation", "reduced activity" and "general fatigue" in MFI-20. No significant change was found on the anxiety index of HADS. The improvements in physical fatigue were associated with changes in the metabolism of lipids, bile acids, the urea cycle and several sugars. Moderate-to-high intensity exercise with person-centered guidance decreased fatigue and improved symptoms of depression and were accompanied by metabolic changes in older adults with RA.
30316460 Are prognostic factors adequately selected to guide treatment decisions in patients with r 2019 Jun OBJECTIVE: To investigate the impact of indicators of unfavorable prognosis ("poor prognostic factors") on the achievement of low disease activity (LDA)/remission in patients with rheumatoid arthritis (RA). METHODS: Biologic DMARD-naïve patients with RA from three observational cohorts were examined. N = 713 patients started their 1st csDMARD, n = 1613 switched to the 2nd csDMARD and n = 388 to the 1st TNF-inhibitor. High disease activity (DAS28 > 5.1), autoantibodies (RF/ACPA positive), prevalent erosions, functional limitation (HAQ ≥ 1.2), comorbidities, obesity (BMI > 30 kg/m(2)), and smoking were evaluated as prognostic factors. Generalized regression analyses were applied to investigate prognostic factors regarding the achievement of LDA (DAS28 < 3.2) or remission (DAS28 < 2.6) within six months. RESULTS: At baseline, RF/ACPA positivity was most frequent in all cohorts (60.3-75.3%), followed by DAS28 > 5.1 (35-57.7%), HAQ ≥ 1.2 (40.5-52.5%), ≥ 2 comorbidities (31.4-54.1%) and erosions (17.1-46.1%). Remission was achieved by 39% (1st-csDMARD), 26% (2nd-csDMARD) and 30% (1st-TNFi). In adjusted regression models DAS28 > 5.1 (OR: 0.41 [0.30;0.56]), HAQ ≥ 1.2 (0.56 [0.42;0.74]), current smoking (0.72 [0.53;0.97], obesity (0.66 [0.49;0.89] and ≥ 2 comorbidities (0.57 [0.40;0.80]) were independently associated with a lower chance to achieve remission within six months (ORs for 2nd-csDMARD). The proportion of patients in LDA/remission declined by 6-12%-points if DAS28 > 5.1 was present at baseline and by 15-27%-points if functional limitation, comorbidities and obesity were additionally present. In all cohorts RF/ACPA positivity and erosions were not associated with achieving LDA/remission. CONCLUSIONS: While RF/ACPA status and erosions do not affect the achievement of LDA/remission, high disease activity, functional limitation, comorbidities and obesity should be considered as unfavorable prognostic factors in patients starting the 1st or 2nd DMARD strategy.
30915732 Diagnostic values of serum IL-10 and IL-17 in rheumatoid arthritis and their correlation w 2019 Mar OBJECTIVE: This study aimed to investigate the diagnostic values of serum IL-10 and IL-17 in rheumatoid arthritis (RA) and their correlation with serum protein. PATIENTS AND METHODS: A retrospective analysis was performed on 116 RA patients admitted to the Yantaishan Hospital (the RA group) and 116 healthy subjects (the control group). Enzyme-linked immunosorbent assay was used to detect the expression levels of serum interleukin (IL)-10, IL-17 and 14-3-3η protein. Pearson analysis was performed to analyze the correlation between the expression levels of serum IL-10, IL-17 and 14-3-3η protein of patients in the RA group, and ROC curve analysis was conducted to measure the diagnostic values of IL-10, IL-17 and their combination in RA. RESULTS: Patients in the RA group had significantly lower serum IL-10 level and markedly higher IL-17 and 14-3-3η protein levels than those in the control group (p<0.001). Serum IL-10 level was negatively correlated with 14-3-3η protein level in RA patients (r=-0.582, p<0.001). Serum IL-17 level was positively correlated with 14-3-3η protein level in RA patients (r=0.482, p<0.001). Serum IL-10 level was negatively correlated with IL-17 level in RA patients (r=-0.468, p<0.001). The AUC of IL-10 for diagnosing RA was 0.671, with a 95% confidence interval of 0.602-0.741 and a cut-off value of 87.315. The AUC of IL-17 for diagnosing RA was 0.856, with a 95% confidence interval of 0.807-0.905 and a cut-off value of 87.844. The AUC of IL-10 combined with IL-17 for diagnosing RA was 0.887. CONCLUSIONS: RA patients had remarkably lower serum IL-10 level and significantly higher IL-17 and 14-3-3η protein levels than healthy people. IL-17 has better sensitivity and specificity than IL-10 for diagnosing RA. IL-10 combined with IL-17 is beneficial to improve the diagnostic level of RA, which provides the reference for the diagnosis, treatment and pathogenesis of RA.
32955222 Coping strategies observed in women with rheumatoid arthritis. 2020 Sep 11 When faced with a chronic disease such as rheumatoid arthritis, the patient attempts to cope with the stressful situation by applying coping strategies. The main aim of rheumatoid treatment is not only improving health but also increasing the quality of life. The research objective was to determine the relationship among socio demographic factors, duration of the disease and its associated ailments, attitude to the disease, self-assessment of one's knowledge of RA, and the application of coping strategies in stressful situations by women with rheumatoid arthritis. The study involved 193 patients of the Clinic of Rheumatology and Systemic Connective Tissue Diseases, and the Rheumatology Unit of the Specialist Outpatient Clinic of the Independent Public Teaching Hospital No. 4 in Lublin, from November 2016 - June 2017. The Coping Orientations to Problems Experienced Inventory (COPE) Questionnaire and an author's Original Questionnaire were used in the study. Analysis of variance (ANOVA) and Tukey's range test were applied for statistical analysis. A p-value<0.05 defined the statistical differences. Analysis was performed using the commercial SPSS Statistics 19 software (IBM Corp., Armonk, NY, USA). The respondents usually use instrumental social support (11.5±1.7), focus on and vent emotions (11.4±1.9), use emotional social support (11.4±1.8), employ active coping (11.4±2.1) and positive reinterpretation and growth (11.2±1.8), and least often rely on their sense of humour (5.5±1.4) or use alcohol or drugs (5±1.1). The factors which determine the types of strategy used are age, education, the duration of the disease, ailments experienced, and attitude towards the disease. Those respondents who declared a greater knowledge of RA more often applied positive reinterpretation and growth, and more rarely used alcohol or drugs. In the treatment and rehabilitation processes it is important to reinforce in the patient positive expectations for the treatment, seek advantages and benefits in one's present health status, and educate patients about the disease, its therapy and appropriate coping strategies.
31578102 Axillary lymph-node metabolic activity assessment on (18)F-FDG-PET/CT in rheumatoid arthri 2020 Mar Objective: Recent studies have provided new insights into the role of lymph nodes (LNs) in rheumatoid arthritis (RA). The aim of this study was to evaluate the metabolic activity of the axillary LNs in relation to that of the upper limb joints and the clinical assessment of disease activity in RA patients treated with biologic therapies.Method: (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography ((18)F-FDG-PET/CT) scans were acquired for 64 patients with RA at baseline and after 6 months of biologic therapy, and the patients' clinical status was evaluated. The maximum standardized uptake value (SUV(max)), metabolic active volume, and total lesion glycolysis (TLG) were used to assess glucose metabolism in the LNs and 12 joints. Clinical evaluations included serum markers and the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate (DAS28-ESR).Results: Changes in the SUV(max) and TLG for the axillary LNs correlated significantly with those of the ipsilateral wrist joints. There was a positive correlation between the changes in the three metabolic parameters of the axillary LNs and the changes in disease activity after treatment. After 6 months of biologic therapy, all metabolic parameters for the axillary LNs in patients with a DAS28-ESR < 3.2 were significantly lower than those of patients with a DAS28-ESR ≥ 3.2.Conclusion: A relationship between the glucose metabolism of the axillary LNs and the ipsilateral wrist joints was demonstrated by the (18)F-FDG-PET/CT parameters. The metabolic activity and active volume of axillary LNs may reflect the therapeutic response to the biologic treatment of RA.
31926494 Genetic Polymorphism and Serum Levels of RORc2 in Rheumatoid Arthritis. 2019 Jul RORc2 is the master transcription factor of T helper 17 cells. We aimed to evaluate whether RORc2 genetic polymorphism and serum levels have association with the risk and activity of rheumatoid arthritis (RA). RORC genetic polymorphisms were investigated by real time PCR. Serum RORc2 protein levels were determined by enzyme-linked immunosorbent assay. Protective effects of rs370515 CT, rs370515 CT + TT, rs3828057 CT, rs3828057 CT+TT and rs9826 GG genotypes were detected. The genotype-phenotype analysis showed no significant differences in the disease activity score 28 (DAS 28) under the recessive versus dominant genotypes. RORc2 protein serum levels were significantly higher in RA patients than controls (P= 0.001) and had a positive correlation with DAS-28. In conclusions, RORC genetic polymorphisms correlate with the risk but not activity of RA, whereas RORc2 serum levels have a positive correlation with both risk and activity of RA.
31646431 Should ultrasound be used routinely in the diagnosis of rheumatoid arthritis? 2020 May INTRODUCTION: A growing body of evidence indicates the benefits of early diagnosis of rheumatoid arthritis (RA) and prompt treatment with disease-modifying anti-rheumatic drugs (DMARDS) in terms of relieving symptoms, improving prognosis, and reducing long-term complications. There is however some controversy over the most beneficial method of imaging in providing accurate early diagnosis. Though current practice favours clinical and radiological assessment, this is increasingly supplemented by ultrasound techniques (and, to a lesser extent, CT and MRI scanning). While EULAR and ESSR favour the use of ultrasonography (US) as the first-line investigation in cases of suspected RA, a recent NICE review upholds the traditional place of plain film radiographs of hands and feet to detect erosions as early signs of synovitis. This review considers the evidence for US in the early diagnosis of RA and the case for it becoming the primary assessment modality in rheumatology clinics. AIMS: This paper aims to assess the current literature on the efficacy of ultrasonography in diagnosing early RA, by comparing US with alternative imaging modalities. The goal is to propose the most appropriate method of diagnosis to improve early initiation of DMARD treatment for optimum disease outcomes. METHODS: Searches for related studies and review articles were carried out using electronic databases and hand searches. Additional references were gleaned from the bibliographies of included papers. Related articles and pop-outs from PubMed were also used. The search was refined in PubMed, by only using reviews which were written in English and published in past 10 years and had full free text available. RESULTS: This review confirms that US has a high level of sensitivity in diagnosing RA (and hence a low risk of missing cases of RA which might benefit from early treatment with DMARDs). It also has a high level of specificity (and hence a low risk of falsely diagnosing somebody with RA who may suffer adverse effects of DMARD therapy). US is already widely available and well accepted by clinicians and patients. It does not involve exposure to radiation and can be readily delivered by appropriately trained staff. CONCLUSION: This review of relevant studies indicates that US should become accepted as the investigation with the most favourable balance of benefits to risks in the early diagnosis of RA. Given the continuing controversy surrounding studies of different imaging techniques in RA, further research into the diagnostic role of US in RA is indicated.
31080194 Synovial Fat Deposition of the Knee Is Associated with Degenerative Joint Disorder. 2019 May Synovial fat deposition, also known as lipoma arborescens, is a rare articular disorder with villous synovial proliferation, commonly seen in the knee. We explored the relationship between the degree of synovial fat deposition on the magnetic resonance imaging (MRI) and the severity of degenerative joint disorder, also called osteoarthritis, on plain radiography. The enrolled patients underwent MRI with a 0.4T permanent magnetic unit in a single institution over a 9-month period. The indications of MRI were chronic knee disorder of non-specific cause. Patients with minor trauma were also included. Consecutive 1,091 knees of 1,075 patients were assessed for the degree of synovial fat deposition on MRI and the severity of degenerative joint disorder on plain radiography. The degenerative joint disorder was graded by radiographic features obtained within one month from MRI using Kellgrene-Lawrence (K-L) scores. MRI features of synovial fat deposition were classified as none, mild and severe. Synovial fat deposition was identified in 30 knees of 29 patients (2.7%) (11 men and 18 women; aged from 25 to 86 years, one patient with bilateral lesions): one female patient with osteoarthritis secondary to rheumatoid arthritis and 28 patients with degenerative joint disorder. The K-L grade was 4 in the case of rheumatoid arthritis. There was a moderate positive correlation between the K-L grade and fat deposition grade (correlation coefficient: 0.59, p < 0.001). Thus, synovial fat deposition was noted in the advanced degenerative joint disorder. We propose that fat deposition represents a nonspecific secondary phenomenon of degenerative joint disorder.
31652652 Association of the Rheumatoid Arthritis Severity Variant rs26232 with the Invasive Activit 2019 Oct 22 rs26232, located in intron one of C5orf30, is associated with the susceptibility to and severity of rheumatoid arthritis (RA). Here, we investigate the relationship between this variant and the biological activities of rheumatoid arthritis synovial fibroblasts (RASFs). RASFs were isolated from the knee joints of 33 RA patients. The rs26232 genotype was determined and cellular migration, invasion, and apoptosis were compared using in vitro techniques. The production of adhesion molecules, chemokines, and proteases was measured by ELISA or flow cytometry. Cohort genotypes were CC n = 16; CT n = 14; TT n = 3. In comparison with the RASFs of the CT genotype, the CC genotype showed a 1.48-fold greater invasiveness in vitro (p = 0.02), 1.6-fold higher expression intracellular adhesion molecule (ICAM)-1 (p = 0.001), and 5-fold IFN-γ inducible protein-10 (IP-10) (p = 0.01). There was no association of the rs26232 genotype with the expression levels of either total C5orf30 mRNA or any of the three transcript variants. The rs26232 C allele, which has previously been associated with both the risk and severity of RA, is associated with greater invasive activity of RASFs in vitro, and with higher expression of ICAM-1 and IP-10. In resting RASFs, rs26232 is not a quantitative trait locus for C5orf30 mRNA, indicating a more complex mechanism underlying the genotype‒phenotype relationship.
30764871 What is the additional value of MRI of the foot to the hand in undifferentiated arthritis 2019 Feb 14 BACKGROUND: MRI-detected subclinical joint inflammation in the hand joints of patients with undifferentiated arthritis (UA) predicts progression to rheumatoid arthritis (RA). It is unknown if adding MRI of the foot increases predictive accuracy compared to the hand alone. METHODS: 1.5-T contrast-enhanced MRI of the unilateral foot (MTP-1-5) and hand (MCP-2-5 and wrist) was performed in 123 patients presenting with UA (not fulfilling the 2010 RA criteria) and scored for bone marrow edema (BME), synovitis and tenosynovitis. Symptom-free controls (n = 193) served as a reference for defining an abnormal MRI. Patients were followed for RA development ≤ 1 year, defined as fulfilling the classification criteria or initiation of disease-modifying antirheumatic drugs because of the expert opinion of RA. The added predictive value of foot MRI to hand MRI was evaluated. RESULTS: Fifty-two percent developed RA. Foot tenosynovitis was predictive (OR 2.55, 95% CI 1.01-6.43), independent of BME and synovitis (OR 3.29, 95% CI 1.03-10.53), but not independent of CRP and number of swollen joints (OR 2.14, 95% CI 0.77-5.95). Hand tenosynovitis was also predictive independent of BME and synovitis (OR 3.99, 95% CI 1.64-9.69) and independent of CRP and swollen joints (OR 2.36, 95% CI 1.04-5.38). Adding foot tenosynovitis to hand tenosynovitis changed the sensitivity from 72 to 73%, specificity from 59 to 54% and AUC from 0.66 to 0.64; the net reclassification index was - 3.5. CONCLUSION: MRI-detected tenosynovitis of the foot predicts progression to RA. However, adding MRI of the foot does not improve the predictive accuracy compared to MRI of the hand alone. In view of cost reduction, the performance of foot MRI for prognostic purposes in UA can be omitted.
31054942 Abatacept modulates CD80 and CD86 expression and memory formation in human B-cells. 2019 Jul BACKGROUND: Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits T-cell activation and is expressed on T-regulatory cells. Human CTLA-4 deficiency results in severe immune dysregulation. Abatacept (CTLA-4 Ig) is approved for the treatment of rheumatoid arthritis (RA) and its mechanism of action is attributed to effects on T-cells. It is known that CTLA-4 modulates the expression of its ligands CD80 and CD86 on antigen presenting cells (APC) by transendocytosis. As B-cells express CD80/CD86 and function as APC, we hypothesize that B-cells are a direct target of abatacept. OBJECTIVES: To investigate direct effects of abatacept on human B-lymphocytes in vitro and in RA patients. METHODS: The effect of abatacept on healthy donor B-cells' phenotype, activation and CD80/CD86 expression was studied in vitro. Nine abatacept-treated RA patients were studied. Seven of these were followed up to 24 months, and two up to 12 months only and treatment response, immunoglobulins, ACPA, RF concentrations, B-cell phenotype and ACPA-specific switched memory B-cell frequency were assessed. RESULTS: B-cell development was unaffected by abatacept. Abatacept treatment resulted in a dose-dependent decrease of CD80/CD86 expression on B-cells in vitro, which was due to dynamin-dependent internalization. RA patients treated with abatacept showed a progressive decrease in plasmablasts and serum IgG. While ACPA-titers only moderately declined, the frequency of ACPA-specific switched memory B-cells significantly decreased. CONCLUSIONS: Abatacept directly targets B-cells by reducing CD80/CD86 expression. Impairment of antigen presentation and T-cell activation may result in altered B-cell selection, providing a new therapeutic mechanism and a base for abatacept use in B-cell mediated autoimmunity.
31309487 Cysteinyl leukotriene receptor antagonism: a promising pharmacological strategy for loweri 2019 Oct BACKGROUND AND AIMS: Though cyclooxygenase inhibitors are employed in rheumatoid arthritis treatment, modulators of leukotrienes are underexplored. We investigated the therapeutic potential of montelukast, a known cysteinyl leukotriene receptor-1 (CysLT1) inhibitor in an experimental rat model of arthritis. METHODS: Arthritis was induced in rats, and montelukast (5 mg/kg body wt.) was administered prophylactically (PAM) and therapeutically (TAM) through oral route. RESULTS AND DISCUSSION: Blood and joint tissue markers of oxidative stress (lipid peroxidation, protein carbonyls, and nitric oxides) were significantly (p < 0.05) reduced in montelukast administered rats. Paw inflammation, RA markers (RF and CRP), eicosanoids (PGE(2), LTB(4), and LTC(4)), cytokines (IL-1β and MCP-1), activity of hydrolytic enzymes (collagenase, elastase, and hyaluronidase), expression of matrix metalloproteinases (MMP), and EP-4 receptor were significantly (p < 0.05) reduced in montelukast administered rats. This study established that leukotriene inhibition through montelukast lowered the severity of arthritis and thus a potential strategy for reducing the severity of arthritis.
30707271 Prospective Follow-Up of Cortical Interruptions, Bone Density, and Micro-structure Detecte 2019 Jun OBJECTIVES: The purpose of the study was to prospectively investigate change (repair or progression) in the number, surface area and volume of cortical interruptions, bone density (vBMD) and micro-structural parameters assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in finger joints of patients with rheumatoid arthritis (RA) treated with synthetic disease modifying anti-rheumatic drugs (sDMARDs) and/or biologic DMARDs (bDMARDs) over a 1-year follow-up period, and in comparison with healthy subjects (HS). METHODS: Thirty-two patients with RA (221 joints, 53% on bDMARDs) and 32 HS (117 joints) were assessed at baseline and after 1 year using semi-automatic analysis of HR-pQCT images. Mean changes (group level) and the proportion of joints (joint level) with changes beyond the least significant change were calculated. RESULTS: At baseline, 530 interruptions were identified in patients, and 136 in HS. The mean of the interruption parameters did not significantly change in either group Mean vBMD decreased more in patients than in HS (- 4.4 versus - 1.1 mgHA/cm(3), respectively). In patients versus HS, proportionally more joints showed repair in interruption volume (6.6% versus 1.7%, respectively) and loss of vBMD (26.7% versus 12.9%, respectively). In patients on sDMARDs versus patients on bDMARDs, proportionally more joints showed progression in the number of interruptions and loss of vBMD (6.1% versus 1.8% and 31.3% versus 17.2%, respectively). CONCLUSIONS: HR-pQCT is able to quantify bone repair and progression. Cortical interruption-, vBMD-, and micro-structure were impaired in RA, of which vBMD and micro-structure further deteriorated, particularly in patients on sDMARDs.
31273939 Circulating miR-99b-5p as a novel predictor of erosion progression on high-resolution peri 2019 Sep OBJECTIVES: To compare micro RNA (miRNA) expression: (a) between healthy individuals and early rheumatoid arthritis (ERA) patients with and without erosion on high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline; and (b) to explore whether these miRNAs could inform a signature predictive of erosion progression despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODS: The second metacarpophalangeal head (MCP2) was scanned by HR-pQCT at baseline and 1 year in 117 ERA patients. We performed global profiling of 377 miRNAs in 10 ERA patients with and without erosion on HR-pQCT at baseline and six healthy controls. Validation of the miRNAs of interest were conducted using TaqMan(®) quantitative real-time polymerase chain reaction in the validation ERA cohort (n = 117) at baseline. Correlation between the candidate miRNAs and erosion progression over 1 year were also assessed. RESULTS: In the 377 screened miRNAs, 94 (60.6%) miRNAs were upregulated in patients with erosions, with 13 (8.4%) upregulated more than 2-fold. Sixty-one (39.4%) miRNAs were downregulated in patients with erosions, with 6 (3.9%) downregulated more than 2-fold. Expression of miR-143-3p, miR-145-5p and miR-99b-5p were significantly higher in the plasma of ERA patients with erosions compared with those without erosions. Logistic regression analysis revealed that the baseline expression of miR-99b-5p was an independent predictor of erosion progression at month 12 (Exp [B] = 4.257, 95% CI 1.178-15.386, P = 0.027). CONCLUSIONS: Differential expressions of circulating miR-143-3p, miR-145-5p and miR-99b-5p in the plasma of ERA patients may characterize a severe form of the disease. MiR-99b-5p, in particular, may serve as a possible predictor for erosion progression.
31469852 Implicit and explicit attitudes towards disease-modifying antirheumatic drugs as possible 2019 OBJECTIVE: This study aims to explore the contribution of implicit attitudes and associations towards conventional disease-modifying antirheumatic drugs (cDMARDs), alongside explicit measures, on medication-taking behaviour and clinical outcomes in adult patients with rheumatoid arthritis (RA). METHODS: In this observational study, implicit attitudes (positive-negative) and health-related associations (health-sickness) were measured with Single Category Implicit Association Tests, whereas explicit outcomes were measured with a bipolar evaluative adjective scale and the Beliefs about Medicines Questionnaire Specific. The primary outcome of this study was medication-taking behaviour subjectively measured by self-report (i.e. validated Compliance Questionnaire on Rheumatology) and objectively measured with electronic drug monitors over a 3 month period. Spearman rank correlations were used to describe correlations between implicit and explicit outcomes. Nested linear regression models were used to assess the additional value of implicit measures over explicit measures and patient-, clinical-, and treatment-related characteristics. RESULTS: Of the 1659 initially-invited patients, 254 patients with RA agreed to participate in this study. Implicit attitudes correlated significantly with necessity-concerns differential (NCD) scores (ρ = 0.13, P = 0.05) and disease activity scores (ρ = -0.17, P = 0.04), whereas implicit health-related associations correlated significantly with mean scores for explicitly reported health-related associations (ρ = 0.18, P = 0.004). Significant differences in age, number of DMARDs, biologic DMARD use, NCD-scores, and self-reported correct dosing were found between the four attitudinal profiles. Nested linear regression models revealed no additional value of implicit measures in explaining self-reported medication-taking behaviour and clinical outcomes, over and above all other variables. CONCLUSION: Implicit attitudes and associations had no additional value in explaining medication-taking behaviour and clinical outcomes over and above often used explicitly measured characteristics, attitudes and outcomes in the studied population. Only age and NCD scores contributed significantly when the dependent variable was correct dosing measured with self-report.
30478638 [Non-drug treatment of rheumatoid arthritis : An analysis of claims data and a survey of 2019 Mar BACKGROUND: Only small amounts of data are available on the prescription frequency of physical therapies (PT) for patients with rheumatoid arthritis (RA). OBJECTIVE: The aim of the study was to evaluate prescription frequencies of PT considering functional status and sociodemographic factors. MATERIAL AND METHODS: A total of 98,963 adults diagnosed with RA in 2013 were identified in claims data from the BARMER health insurance. A questionnaire was sent to a representative sample of 6193 people requesting information on the disease status. Of these 2535 persons were included who agreed to the linking of the questionnaire and claims data and who confirmed a diagnosis of RA. From the routine claims data the prescription of PT and occupational therapy as well as the medical discipline of the prescribing physician were analyzed. Multivariable logistic regression was conducted to determine which variables (age, sex, M05/M06 diagnosis, residential area, income, functional status and rheumatological care) were associated with the use of PT. RESULTS: In 2015 a total of 47% of the study population received PT (35% physiotherapy, 15% thermotherapy, 15% manual therapy, 2% electrotherapy and 6% massage) and 3% occupational therapy. Of the PT prescriptions 37% were issued by general practitioners, 27% by orthopedists and 18% by rheumatologists. Women and persons living in the eastern states of Germany and patients with high functional impairment were prescribed PT more often. Income, educational status, seropositivity and rheumatological care did not have any influence on the frequency of prescription of PT. CONCLUSION: There are deficits in the outpatient prescription of PT but without indications of an undersupply of population groups due to low socioeconomic status. In contrast to the prescription of disease-modifying antirheumatic drug (DMARD) treatment, PT is predominantly prescribed by general practitioners.
31501076 Meta-analysis of preclinical studies of mesenchymal stromal cells to treat rheumatoid arth 2019 Sep BACKGROUND: This study aims to evaluate the quality of preclinical data, determine the effect sizes, and identify experimental measures that inform efficacy using mesenchymal stromal (or stem) cells (MSC) therapy in animal models of rheumatoid arthritis (RA). METHODS: Literature searches were performed on MSC preclinical studies to treat RA. MSC treatment effect sizes were determined by the most commonly used outcome measures, including paw thickness, clinical score, and histological score. FINDINGS: A total of 48 studies and 94 treatment arms were included, among which 42 studies and 79 treatment arms reported that MSC improved outcomes. The effect sizes of RA treatments using MSC, when compared to the controls, were: paw thickness was ameliorated by 53.6% (95% confidence interval (CI): 26.7% -80.4%), histological score was decreased by 44.9% (95% CI: 33.3% -56.6%), and clinical score was decreased by 29.9% (95% CI: 16.7% -43.0%). Specifically, our results indicated that human umbilical cord derived MSC led to large improvements of the clinical score (-42.1%) and histological score (-51.4%). INTERPRETATION: To the best of our knowledge, this meta-analysis is to quantitatively answer whether MSC represent a robust RA treatment in animal models. It suggests that in preclinical studies, MSC have consistently exhibited therapeutic benefits. The findings demonstrate a need for considering variations in different animal models and treatment protocols in future studies using MSC to treat RA in humans to maximise the therapeutic gains in the era of precision medicine. FUNDS: NIH [1DP2CA195763], Baylx Inc.: BI-206512, NINDS/NIH Training Grant [Award# NS082174].
31117160 Reactivation of hepatitis B virus infection following rituximab treatment in HBsAg-negativ 2019 Jun AIM: Longitudinal data of the reactivation of hepatitis B virus (rHBV) and serial serological markers or HBV-DNA has been limited. This study aimed to investigate the temporal course of rHBV development in rheumatoid arthritis (RA) patients undergoing long-term rituximab therapy. METHODS: The occurrence of rHBV was examined in 157 RA patients during rituximab therapy. Serum levels of HBV surface antigen (HBsAg), HBV core antibody (HBcAb), and HBsAb were determined by electrochemiluminescence immunoassays, and viral loads by real-time polymerase chain reaction assay. RESULTS: Among 157 patients undergoing rituximab therapy, 103 (65.6%) were HBsAg-negative and HBcAb-positive. Before rituximab therapy, 20 (19.4%) of these 103 patients were HBsAb-negative, while 83 (80.1%) were HBsAb-positive. Five (20%) HBsAb-negative patients developed rHBV after rituximab therapy. Among 83 HBsAb-positive patients, 4 (4.8%) developed rHBV. Among 9 patients with rHBV, 7 (77.7%) exhibited HBsAg seroreversion. Significant decline of HBsAb titers (mean ± SD, 296.0 ± 417.3 mIU/mL at baseline vs 187.0 ± 332.5 mIU/mL after rituximab therapy, P < 0.001) was observed in HBsAg-/HBsAb + patients. All HBsAg-negative patients who developed rHBV during rituximab therapy were characterized by baseline HBsAb titers < 100 mIU/mL and negative HBsAb at the time of rHBV. HBsAb positivity was an independent protective factor for rHBV (hazards ratio: 0.14, 95% CI: 0.03-0.62, P = 0.009). CONCLUSION: Baseline HBsAb positivity was a significant protective factor for rHBV in HBsAg-negative, HBcAb-positive RA patients receiving rituximab therapy.
31703796 The prevalence and impact of comorbid fibromyalgia in inflammatory arthritis. 2019 Jun Fibromyalgia (FM) is one of the most common conditions that rheumatologists encounter. It is characterised by chronic widespread pain, fatigue, sleep disturbances and impaired cognition. The prevalence of comorbid FM among populations with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are considerably higher than among the general population, with pooled prevalence estimates of 18-24% in RA, 14-16% in axSpA and 18% in PsA. Prevalence estimates should be interpreted with care as the criteria for FM have not been validated for use in patients with inflammatory arthritis. Comorbid FM appears to affect assessment of disease severity in these conditions, particularly patient-reported outcome measures, and may influence response to treatment. There is a need for better identification, classification and management of FM in the context of inflammatory rheumatic diseases.