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ID PMID Title PublicationDate abstract
32951253 The value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as comple 2021 Jan BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have drawn attention in recent years as novel non-specific inflammatory markers; however, only a few studies have been conducted to investigate their value in RA. OBJECTIVE: To investigate the value of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as complementary diagnostic tools in rheumatoid arthritis (RA). METHOD: This study included 1009 patients with RA, 170 patients with other rheumatic diseases, and 245 healthy individuals from four medical centers. The patients' general data, including complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF), were retrospectively analyzed, and the NLR and PLR were calculated. Potential effective indicators were screened by logistic regression analysis, and a receiver operating characteristic (ROC) curve was plotted to evaluate their diagnostic value for RA. RESULTS: (a) The NLR and PLR were significantly higher in the RA group than in the non-RA group and the control group (P < .05). (b) Spearman's Rho showed that the NLR was positively correlated with the PLR (r = .584, P < .05), RF (r = .167, P < .01), and CRP (r = .280, P < .01) but was not significantly correlated with ESR (r = .100, P > .05). The PLR was positively correlated with RF (r = .139, P < .01), CRP (r = .297, P < .01), and ESR (r = .262, P < .05). (c) Logistic analysis showed that RF, CRP, ESR, and the NLR had diagnostic value for RA. (d) For the NLR, the area under the curve (AUC) of the ROC curve was 0.831; at the cutoff value of 2.13, the diagnostic sensitivity, specificity, accuracy, and Youden index were 76.7%, 75.9%, 76.4%, and 0.5424, respectively. CONCLUSION: The NLR was less effective than CRP and RF but was superior to ESR in the diagnosis of RA. The NLR can thus be used as a complementary diagnostic indicator in the diagnosis of RA.
32124567 Adherence to subcutaneous anti-TNFα agents in patients with rheumatoid arthritis is large 2020 Apr AIM: The aims of this prospective study were to determine the dimension of adherence in rheumatoid arthritis (RA) patients receiving subcutaneously administered anti-tumor necrosis factor-α (anti-TNFα) agents and to evaluate the influence of injection site pain and skin perceptions following subcutaneous administration of anti-TNFα drugs on patients' adherence. METHOD: An inception cohort of patients starting subcutaneously administered anti-TNFα treatment was enrolled. Injection site pain perception was assessed through the Self-Injection Assessment Pain Questionnaire (SIAPQ), and adherence to treatment was ascertained by the Compliance Questionnaire for Rheumatology (CQR5). Associations between beliefs and non-adherence, and the influence of demographic (age, disease duration, educational level), clinical (body mass index, patient global assessment, physician global assessment, Numerical Rating Scale of pain, Health Assessment Questionnaire-Disability Index, Simplified Disease Activity Index, and comorbidities measured by the modified Rheumatic Disease Comorbidty Index), and radiographic (Simple Erosion Narrowing Score) variables were assessed using logistic regression models. RESULTS: Adherence data over a 12-month interval were available for 193 patients. Of these, 21.7% reported non-adherence to anti-TNFα therapy. No difference (P = .383) was found for anti-TNFα drugs (adalimumab, etanercept, certolizumab pegol and golimumab). In the logistic model, age (P = .0029), higher disease activity (P = .020), low numbers of comorbidity conditions (P = .0004), injection site pain and skin perception (P = .0008), were significantly associated with increased likelihood of medication adherence. CONCLUSION: Adherence is influenced by both demographic characteristics (age) and clinical factors (disease activity, comorbidity burden and injection site pain and skin perception) in RA patients.
31709477 The impact of different criteria sets on early remission and identifying its predictors in 2020 Feb OBJECTIVES: To assess rates of early remission and investigate the concordance across different remission definitions, and to identify predictors of early remission in Chinese patients with rheumatoid arthritis (RA). METHODS: For this study, clinical records were retrospectively reviewed for RA patients at rheumatologic clinic in Peking University First Hospital from 2009 to 2018. Disease activity and remission were determined according to DAS28-ESR, CDAI, SDAI, and Boolean criteria. Early remission was defined as time to remission ≤ 6 months. A secondary definition evaluated early remission as ≤ 3 months. Logistic-regression analyses were performed to identify determinants of early remission. RESULTS: A total of 869 consecutive patients contributing 8640 clinic visits were studied. Early remission rates were respectively 42.0% (DAS28-ESR), 25.0% (CDAI), 29.4% (SDAI), and 26.1% (Boolean). Notably, patients achieving remission within 6 months more frequently attained sustained remission in contrast to those not achieving early remission (68.7-75.1% vs. 31.2-33.1%, p < 0.0001). Further logistic-regression analyses revealed male, early RA, as well as initial hydroxycloroquine treatment were independently associated higher probability of early remission, as demonstrated by nearly all definitions, while a higher baseline disease activity (DAS28-ESR, CDAI, and SDAI) lowered the possibility of early remission in corresponding remission indices. The significant associations of treatment-naïve, serological features with early remission were not confirmed. CONCLUSIONS: Early remission was strongly associated with sustained remission, however. infrequently achievable in real-life practice. Male, early RA, a low baseline disease activity, and initial hydroxycloroquine treatment were stable independent predictors of early remission.Key Points• Early remission was infrequently achievable in real-life practice, especially measured by stringent indices.DAS28-based early remission appears to be the loosest criterion and the remaining three broadly agreed with each other.• Early remission was significantly associated with sustained remission.• Male, early RA, a low baseline disease activity, and initial hydroxycloroquine treatment were positively correlated with early remission.
32975562 "A Necessary Investment in Future Health": Perceptions of Physical Activity Maintenance Am 2020 Dec 7 OBJECTIVE: A few studies with a qualitative design have addressed physical activity (PA) maintenance in people with rheumatoid arthritis (RA), but none of them focused specifically on maintenance of PA according to public health recommendations. The purpose of this study was to describe perceptions of PA maintenance during the second year of an outsourced 2-year support program among people with RA. METHODS: For this descriptive design with a qualitative inductive approach, semi-structured interviews were conducted with 18 participants with RA (3 men and 15 women). Variation in age, disease duration, activity limitation, pain, levels of PA, and PA maintenance was targeted through strategic sampling. Qualitative content analysis was used, and a pattern of theme, subthemes, and categories was constructed based on the participants' perceptions of PA maintenance. RESULTS: A main overarching theme, "A necessary investment in future health"-with 3 subthemes of dedication, awareness, and affinity-was identified as participants' perceptions of PA maintenance. Eight categories further described are a changed mindset, habits, commitments, monitoring, insights in PA, health gains, social support, and PA context. CONCLUSIONS: PA according to public health recommendations was perceived as a true investment in future health and wellness requiring dedication, awareness, and affinity. To promote PA maintenance, physical therapists working with people with chronic conditions should consider strengthening these prerequisites by targeting patients' negative attitudes to PA, supporting their creation of PA habits to incorporate in daily routines, introducing monitoring of PA intensity, supporting development of PA self-regulation skills, and providing suitable gym facilities with the possibility of peer support.
31939225 Quantification of joint blood flow by dynamic contrast-enhanced near-infrared spectroscopy 2020 Jan SIGNIFICANCE: Current guidelines for rheumatoid arthritis (RA) management recommend early treatment with disease modifying antirheumatic drugs (DMARDs). However, DMARD treatment fails in 30% of patients and current monitoring methods can only detect failure after 3 to 6 months of therapy. AIM: We investigated whether joint blood flow (BF), quantified using dynamic contrast-enhanced time-resolved near-infrared spectroscopy, can monitor disease activity and treatment response in a rat model of RA. APPROACH: Ankle joint BF was measured every 5 days in eight rats with adjuvant-induced arthritis (AIA) and four healthy controls. Arthritis was allowed to progress for 20 days before rats with AIA were treated with a DMARD once every 5 days until day 40. RESULTS: Time and group had separate significant main effects on joint BF; however, there was no significant interaction between time and group despite a notable difference in average joint BF on day 5. Comparison of individual blood flow measures between rats with AIA and control group animals did not reveal a clear response to treatment. CONCLUSIONS: Joint BF time courses could not distinguish between rats with AIA and study controls. Heterogeneous disease response and low temporal frequency of BF measurements may have been important study limitations.
32111860 Peripartum issues in the inflammatory arthritis patient: A survey of the RAPPORT registry. 2020 Feb 28 Childbearing women with rheumatoid (RA) and psoriatic arthritis (PsA) have significant peripartum issues. A retrospective anonymous RedCAP survey of peripartum period in females with RA/PsA in the RAPPORT registry was performed. Completed analyses included descriptive statistics, Chi-square and Fisher's exact test. 162 patients (133 RA/29 PsA) completed the survey (103 women having 234 pregnancies), 164 pregnancies occurring before and 70 pregnancies occurring after diagnosis. Pregnancy outcomes from 103 patients included: 96% live births, 1.9% stillbirths, 23% miscarriages, and 15% therapeutic abortions. A third of patients had fewer children than desired due to disease activity, medications and other reasons. For 63 pregnancies after diagnosis: (1) 49% of pregnancies received pre-conception counseling; (2) 65% described good disease control during pregnancy but 74% flared in the first 3 months postpartum; (3) 79% of pregnancies discontinued IA medications; (4) 35% of pregnancies occurred on biologic therapy at or prior to conception. Gestational age at time of delivery was 37-40 weeks in 58% (33/57) post-arthritis vs 66% (83/126) pre-arthritis pregnancies. No statistically significant differences occurred between pregnancies before or after RA/PsA diagnosis for: pregnancy planning, fertility treatment, pregnancy and labour/delivery complications, birth defect frequency or neonatal complications. Neonatal ICU admissions were significantly lower in pre- compared to post-arthritis pregnancies (3.2% vs 14.5%). No pregnancy complications were noted in 24/54 pregnancies on medications compared to 6/9 pregnancies not on medications. The impact of RA/PsA before, during and after pregnancy varied considerably in this cohort emphasizing the importance of informed-decision making at all stages.
31324694 Diagnostic value of the serum Midkine in patients with rheumatoid arthritis. 2020 Jan Early diagnosis and detection of rheumatoid arthritis (RA) activity which is a potential therapeutic target, depends mainly on clinical presentation. However, laboratory tests may contribute to diagnosis and disease activity assessment of RA. This study aims to evaluate the accuracy of serum Midkine as serological marker for RA diagnosis and its activity detection. All patients with RA were recruited during the period from January 2016 to August 2018 in addition to healthy subjects as control. Serum Midkine level was estimated using enzyme immunoassay. The accuracy was determined for serum Midkine against the used American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for RA diagnosis and disease activity score derivative for 28 joints-erythrocyte sedimentation rate (ESR) score for assessment of RA disease activity. A total of 211 of patients with RA (group I) were enrolled in this study with 112 healthy subjects (group II). Patients with RA were divided into two subgroups according to the disease activity; patients with active RA (group IA) and RA in remission (group IB). We detected that the area under curve (AUC) of serum Midkine level (AUC=0.851) was significantly lower than that of rheumatoid factor IgM and anti-cyclic citrullinated peptide IgG for RA diagnosis. However, Midkine presents a significantly higher diagnostic accuracy (AUC=0.939) in detecting RA activity than that offered by C reactive protein (CRP) or ESR. Our study suggested that serum Midkine is a potential serological marker for detection of active inflammatory state with higher diagnostic accuracy than other inflammatory markers as CRP or ESR. Therefore, it can be used as an inflammatory marker for detection of disease activity rather than diagnosis of RA.
30557057 Fibrosis-4 index at diagnosis can predict all-cause mortality in patients with rheumatoid 2020 Jan Objectives: Comorbidities and conventional risk factors influence the prognosis of patients with rheumatoid arthritis (RA). We investigated whether liver fibrosis burden is associated with all-cause mortality in patients with RA.Methods: A total of 2812 patients with RA were retrospectively selected and reviewed. Liver fibrosis was assessed using the fibrosis-4 index (FIB-4) [age (years)× aspartate aminotransferase level (IU/L)/platelet count (10(9)/L)/√alanine aminotransferase (IU/L)].Results: The mean patient age was 51.5 years (482 men and 2330 women). The mean erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and FIB-4 were 43.5 mm/h, 9.0 mg/L, and 1.0, respectively. Methotrexate was used in 2524 (89.9%) patients, and biological or targeted synthetic disease-modifying antirheumatic drugs were used in 310 (11.0%) patients. During the follow-up period (mean 93.7 months), 89 (3.2%) patients died. Deceased patients had a significantly higher age (mean 64.4 vs. 51.1 years); frequency of male sex (31.5% vs. 16.7%), hypertension (HTN; 40.4 vs. 18.5%), and diabetes mellitus (DM; 25.8% vs. 7.7%); ESR (mean 57.1 vs. 43.0 mm/h); CRP (mean 16.9 vs. 8.7 mg/L); and FIB-4 (mean 1.5 vs. 1.0) (all p < .05) than the survivors. On multivariate analysis, higher FIB-4 was found to be independently associated with a higher rate of all-cause mortality (hazard ratio =1.130, p = .004), together with male sex, HTN, DM, ESR, and intensity of glucocorticoid exposure, whereas the use of methotrexate was independently protective (all p < .05).Conclusion: Besides conventional risk factors, fibrotic burden, assessed using FIB-4, might be useful for risk stratification of patients newly diagnosed as having RA.
31644400 Study of Monocytes/Macrophages Stimuli as the Targets of Treating Inflammatory Bone Diseas 2020 Inflammation is the most common pathology in many orthopedic diseases, such as: rheumatoid arthritis (RA), osteoarthritis (OA) and other reasons caused osteolysis. The leading factor of inflammation was considered as the differentiation of monocyte and the polarization of macrophage. However, cytokines and different cell models could regulate this progress in some aspects. Therefore, in the current review, we summarize several cytokines and cell models, which could lead to inflammatory orthopedic diseases via regulating monocytes and macrophages. In order to extensively explore the potential therapeutic and medicine targets for inflammation-induced bone diseases.
32446651 Development of a process to improve medication adherence in patients with rheumatoid arthr 2020 May OBJECTIVE: To develop a disease-specific patient questionnaire to be used during monthly follow-up telephone calls ("refill calls") for patients with rheumatoid arthritis receiving a noninfused biologic medication. SETTING: Independent specialty community pharmacy in North Carolina. PRACTICE DESCRIPTION: Realo Specialty Care was formed to provide a patient-centered care approach to patients with complex, chronic conditions such as HIV/AIDS, hepatitis, rheumatoid arthritis, and plaque psoriasis. The services include medication therapy management, patient education, prior authorization assistance, adverse drug reaction monitoring, and an adherence program. PRACTICE INNOVATION: Using national guidelines, an 8-item questionnaire that addressed overall health, adherence, and adverse medication events for noninfused biologic medications for rheumatoid arthritis was developed. When an eligible patient was identified, a notification was added within the pharmacy's dispensing software. The pharmacist or technician was prompted to use the newly developed questionnaire during the monthly refill call. EVALUATION: Patients' responses were archived in their profiles within the pharmacy's dispensing software. The change in adherence was assessed by the mean medication possession ratio (MPR) before the intervention (July 2018 to September 2018) and monthly after the intervention (November 2018 to February 2019). RESULTS: A total of 29 patients were eligible on the basis of an MPR less than 90%; data from 18 patients were used. The mean MPR increased from 71% preintervention (September 2018) to 75% in the first month after the start of the intervention (November 2018). The mean MPR reached a high of 81% in the fourth month after the start of the intervention (February 2019), representing a 10% increase in the MPR. CONCLUSION: The specialty pharmacy team successfully developed and used the rheumatoid arthritis questionnaire during the monthly refill calls. The implementation of the disease-specific questionnaire led to increased medication adherence and enhanced communication with patients with regard to their health and outcome of therapy.
32911284 Predictive ability, validity, and responsiveness of the multi-biomarker disease activity s 2020 Oct BACKGROUND/OBJECTIVE: We assessed the predictive value, validity, and responsiveness of the multi-biomarker disease activity (MBDA) score in rheumatoid arthritis (RA) patients initiating methotrexate. METHODS: We examined data from a 16-week, open-label study of methotrexate in RA. Disease activity was assessed and the MBDA score was calculated using serum that was collected and banked from baseline and week 16. Multivariable logistic regression models assessed whether MBDA scores predicted treatment response. Pearson correlations assessed the convergent validity and external responsiveness of the MBDA score with other measures of RA disease activity. Internal responsiveness was assessed by calculating standardized response means (SRMs). RESULTS: A total of 130 patients initiated the study, with follow-up MBDA scores available on 95 patients. Baseline MBDA scores did not predict ACR response or achieving low disease activity. Higher baseline DAS28-ESR scores were significantly associated with an ACR20 response (odds ratio 1.89 per unit, 95% CI 1.20-2.96) but not ACR50, ACR70, or low disease activity. The MBDA score moderate-to-weakly correlated with the DAS28-ESR and ESR at baseline and week 16, with weak-to-very weak correlations with patient global and function. Change in MBDA scores moderately correlated with changes in DAS28-ESR and ESR, while weakly correlating with changes in patient global and function. The DAS28-ESR (SRM 1.31) demonstrated greater responsiveness following methotrexate treatment than the MBDA score (SRM 0.71). CONCLUSIONS: MBDA scores did not predict treatment response to methotrexate. The MBDA score weak-to-moderately correlated with baseline and post-treatment disease activity measures and was less responsive to methotrexate-related improvement than the DAS28-ESR.
32906025 Real-world clinical effectiveness of rituximab rescue therapy in patients with progressive 2020 Oct OBJECTIVE: To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with progressive rheumatoid arthritis-related interstitial lung disease (RA-ILD) in whom more conventional therapy has failed. METHODS: Longitudinal retrospective observational study of a cohort of patients with RA-ILD that started treatment with RTX due to ongoing progressive ILD despite treatment with glucocorticoids and csDMARDs or immunosuppressants (IS). All patients were treated with two or more cycles of RTX and evaluated for at least 12 months. Ongoing therapy with csDMARDs or IS remained unchanged. RESULTS: Thirty-one patients were analyzed. Before initiation of RTX the mean decline (delta) in %pFVC and %pDLCO from the ILD diagnosis (median 21 months) was -16.5% and -19.7%, respectively. After 1 year of treatment, RTX was able to reverse the decline of pulmonary function test (PFTs) parameters: ∆%pFVC +8.06% compared to baseline (95% CI: -10.9 to -5.2; p<0.001) and ∆%pDLCO +12.7% (95% CI: -16.3 to -9.1; p<0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 26% of cases. Dividing the population into UIP and non-UIP patterns, we observed a significant increase in PFTs parameters in both groups. In the 25 patients (80.6%) that completed 2 years of treatment, the statistically significant amelioration in PFTs parameters observed at one year was maintained: ∆%pFVC +11.2% (95% CI: -15.6 to -6.8; p<0.001) and ∆%pDLCO +14.8% (95% CI: -19.3 to -10.3; p<0.001). At the end of the follow-up period (median 32 months; IQR 25th-75th 26-64), only 23 of the 31 patients (74.2%) were still undergoing treatment with RTX: in 3 cases (10%) it was stopped due to adverse events, in another 3 (10%) treatment failed ultimately requiring a lung transplant, and 2 patients (6%) died due to progression of the ILD and infectious complications. The frequency of adverse events reached 32% of cases. CONCLUSION: Based on our results, RTX appears to be effective as rescue therapy in a considerable proportion of patients with progressive RA-ILD unresponsive to conventional treatment.
31947680 Understanding the Molecular Mechanisms Underlying the Pathogenesis of Arthritis Pain Using 2020 Jan 14 Arthritis, including osteoarthritis (OA) and rheumatoid arthritis (RA), is the leading cause of years lived with disability (YLD) worldwide. Although pain is the cardinal symptom of arthritis, which is directly related to function and quality of life, the elucidation of the mechanism underlying the pathogenesis of pain in arthritis has lagged behind other areas, such as inflammation control and regulation of autoimmunity. The lack of therapeutics for optimal pain management is partially responsible for the current epidemic of opioid and narcotic abuse. Recent advances in animal experimentation and molecular biology have led to significant progress in our understanding of arthritis pain. Despite the inherent problems in the extrapolation of data gained from animal pain studies to arthritis in human patients, the critical assessment of molecular mediators and translational studies would help to define the relevance of novel therapeutic targets for the treatment of arthritis pain. This review discusses biological and molecular mechanisms underlying the pathogenesis of arthritis pain determined in animal models of OA and RA, along with the methodologies used.
32635659 JAK-Inhibitors for the Treatment of Rheumatoid Arthritis: A Focus on the Present and an Ou 2020 Jul 5 Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and biological drugs. JAKi are characterized by a novel mechanism of action, consisting of the intracellular interruption of the JAK-STAT pathway crucially involved in the immune response. The aim of this narrative review is to globally report the most relevant pharmacological features and clinical outcomes of the developed and incoming JAKi for RA, based on the available preclinical and clinical evidence. A total of 219 papers, including narrative and systematic reviews, randomized controlled trials (RCTs), observational studies, case reports, guidelines, and drug factsheets, were selected. The efficacy and safety profile of both the first generation JAKi (baricitinib and tofacitinib) and the second generation JAKi (upadacitinib, filgotinib, peficitinib, decernotinib and itacitinib) were compared and discussed. Results from RCTs and real-life data are encouraging and outline a rapid onset of the pharmacologic effects, which are maintained during the time. Their efficacy and safety profile are comparable or superior to those of biologic agents and JAKi proved to be efficacious when given as monotherapy. Finally, the manufacturing of JAKi is relatively easier and cheaper than that of biologics, thus increasing the number of compounds being formulated and tested for clinical use.
32662413 ICHIBAN, a non-interventional study evaluating tocilizumab long-term effectiveness and saf 2021 Mar OBJECTIVES: We aimed to measure long-term effectiveness and safety of tocilizumab in patients with rheumatoid arthritis in daily German practice. METHODS: ICHIBAN was a prospective, multi-centre, non-interventional study (ML22928) that enrolled adult patients with active moderate to severe rheumatoid arthritis. Patients were to be treated according to tocilizumab label and observed for up to two years. Effectiveness outcomes included DAS28-ESR remission, EULAR response, CDAI and HAQ. RESULTS: Overall, 3164 patients received at least one dose of tocilizumab. Patient mean age was 55.5±13.1 years (74.8% female). At baseline, 72.1% of patients had at least one comorbidity. Approximately 50.9% of patients received concomitant csDMARDs, mostly methotrexate, and 80.7% received concomitant glucocorticoids (GCs). In patients receiving GCs at baseline, the mean dose decreased from 9.32±16.36 mg/d to 4.60±4.48 mg/d at week 104. In the effectiveness population with no prior TCZ (n=2902), 61.4% of patients achieved the primary outcome, DAS28-ESR remission. Improvements were seen as early as week 4. At week 104, 77.9% of patients had DAS28-ESR low disease activity, 89.6% achieved good or moderate EULAR response, and 29.5% achieved a CDAI-based remission. Effectiveness outcomes were similar in all previous therapy subgroups. The incidence of serious infections was similar to the rates in former studies involving tocilizumab. Patients receiving GC at baseline experienced slightly higher rates of treatment-related serious adverse events, mainly infections. No new safety signals were observed. CONCLUSIONS: Long-term effectiveness and safety in ICHIBAN were in line with previously reported tocilizumab efficacy and safety studies.
32365786 Differentially Expressed Genes of Natural Killer Cells Can Distinguish Rheumatoid Arthriti 2020 Apr 30 Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases, while its molecular triggers are not fully understood. A few studies have shown that natural killer (NK) cells may play either a pathogenic or a protective role in RA. In this study, we sought to explore NK cell markers that could be plausibly used in evaluating the differences among healthy controls and RA patients. Publicly available transcriptome datasets from RA patients and healthy volunteers were analyzed, in order to identify differentially expressed genes (DEGs) between 1. different immune cells as compared to NK cells, and 2. NK cells of RA patients and healthy controls. The identified DEGs were validated using 16 healthy controls and 17 RA patients. Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll density gradient method, while NK cells were isolated using RosetteSep technique. RNA was extracted and gene expression was assessed using RT-qPCR. All selected genes were differentially expressed in NK cells compared to PBMCs. CD56, CXCL16, PECAM-1, ITGB7, BTK, TLR10, and IL-1β were significantly upregulated, while CCL2, CCR4, RELA and IBTK were downregulated in the NK cells of RA patients when compared to healthy controls. Therefore, these NK specific genes might be used as promising biomarkers for RA diagnosis.
31544586 Peptidylarginine deiminase 4 (PAD4) activity in early rheumatoid arthritis. 2020 Mar Objectives: Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes catalysing the conversion of arginine residues to citrulline, which may constitute a risk factor in rheumatoid arthritis (RA) pathogenesis. We investigated PAD activation by serum (PAD(Act)) in early RA, and the associations between PAD activation and disease characteristics, treatment response, and progression of radiographic damage.Method: Sera from disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients (n = 225), classified according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and healthy controls (n = 63) were analysed for PAD4 activating capacity at 0, 3, 12, and 24 months using a high-performance liquid chromatography fluorometric method. Associations for PAD(Act) were evaluated by Mann-Whitney U and chi-squared tests. Changes in PAD(Act) levels were compared using the Wilcoxon signed-rank test.Results: PAD(Act) positivity occurred in 42% (n = 95) of the patients and was more prevalent in anti-citrullinated protein antibody (ACPA)-positive vs ACPA-negative patients (47% vs 20%, p = 0.002), but not in rheumatoid factor (RF)-positive vs RF-negative patients (44% vs 38%, p = 0.49). PAD(Act)-positive were younger than PAD(Act)-negative patients [mean ± sd 48.7 ± 13.5 vs 53.2 ± 13.7 years, p = 0.011]. Median [25th, 75th percentile] PAD(Act) levels were higher in patients than in controls (8768 [7491, 11 393] vs 7046 [6347, 7906], p < 0.0001) and decreased after initiation of DMARD treatment, but were not associated with treatment response or progression of radiographic damage after 2 years of follow-up.Conclusion: Serum capacity to activate PAD4 was associated with ACPA and RF positivity and earlier disease onset in early RA patients, and decreased after initiation of DMARD treatment, indicating that anti-PAD treatment could potentially be beneficial in RA.
31858209 A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation 2020 Mar Increased cardiovascular (CV) morbidity and mortality have been found in rheumatoid arthritis (RA). Tumour necrosis factor α (TNF-α) inhibitors may improve vascular function. In the first part of this study, we determined microcirculation during postoocclusive reactive hyperemia (PORH) representing endothelial function. In a nonselected population (n = 46) we measured flow-mediated vasodilation (FMD) of the brachial artery and laser Doppler flow (LDF) by ultrasound. Among LDF parameters, we determined TH1 (time to half before hyperemia), TH2 (time to half after hyperemia), Tmax (time to maximum) and total hyperemic area (AH). We measured von Willebrand antigen (vWF:Ag) by ELISA. In the second part of the study, we assessed the effects of adalimumab treatment on microcirculatory parameters in 8 early RA patients at 0, 2, 4, 8 and 12 weeks. We found significant positive correlations between FMD and LDF Tmax (R = 0.456, p = 0.002), FMD and TH2 (R = 0.435, p = 0.004), and negative correlation between vWF:Ag and Tmax (R = - 0.4, p = 0.009) and between vWF:Ag and TH2 (R = - 0.446, p = 0.003). Upon adalimumab therapy in early RA, TH2 times improved in comparison to baseline (TH2(baseline) = 26.9 s vs. TH2(4weeks) = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH2(8weeks) = 40.5, p = 0.026; TH2(12weeks) = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AH(baseline) = 1599 Perfusion Units [PU] vs. AH(8weeks) = 2724 PU, p = 0.045). The PORH test carried out with LDF is a sensitive option to measure endothelial dysfunction. TH1 and TH2 may be acceptable and reproducible markers. In our pilot study, treatment with adalimumab exerted favorable effects on disease activity, endothelial dysfunction and microcirculation in early RA patients.
32757727 Major differences in medical and surgical treatment of psoriatic arthritis and rheumatoid 2020 Jul OBJECTIVES: Substantial changes in the handling of patients with inflammatory arthritis have occurred during the past half century. Polyarticular psoriatic arthritis (PsA) has been treated with the same synthetic disease-modifying anti-rheumatic drugs (DMARDs) as rheumatoid arthritis (RA), but for PsA there is less documentation regarding their effect. For biologic DMARDs, evidence of effect is more convincing. We have previously investigated the risk of orthopaedic surgery in patients with RA and PsA to see whether the change in treatment over time has improved the long-term outcome of inflammatory arthritis. For RA, patients diagnosed from 1999 onwards had a lower risk of surgery than patients diagnosed in earlier years. For PsA, the risk of surgery did not change similarly. We wished to compare RA patients to PsA patients with regard to medical and surgical treatment. METHOD: We compared a historic cohort of 1010 RA patients diagnosed in 1972-2009 to a historic cohort of 590 PsA patients diagnosed in 1954-2011. RESULTS: PsA patients received significantly less medical treatment both in the first year of disease and during the disease course. Risk of surgery during the disease course was lower for PsA than for RA (20% vs 31%). The risk of surgery in RA patients diagnosed from 1999 onwards was similar to that of PsA patients. CONCLUSIONS: PsA patients received less intensive treatment than RA patients. Their prognosis, regarding orthopaedic surgery, was also less severe. Contrary to RA, the change in treatment did not have beneficial effects regarding the risk of orthopaedic surgery.
32234405 Autoimmune thyroid disorders and rheumatoid arthritis: A bidirectional interplay. 2020 Jun Rheumatoid arthritis (RA) and autoimmune thyroid disease (AITD) can occur in the same patient in the autoimmune polyglandular syndrome 2. The association of the two conditions has been recognized long-time ago and the prevalence of AITD in patients with RA and vice versa is well assessed. Geographical variation of AITD and related autoantibodies in RA patients is partly due to ethnic and environmental differences of the studied populations. The impacts of thyroid disorders on RA outcome and vice versa are still controversy. In both AITD and RA genetic susceptibility and environmental factors play a synergic role in the development of the diseases. In this review we aimed at investigating the association of AITD and thyroid autoantibodies with RA, the common pathogenic pathways, the correlation with RA disease activity, and influence of the treatment.