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ID PMID Title PublicationDate abstract
32001166 Assessment of structural damage progression in established rheumatoid arthritis by convent 2019 Oct Structural damage progression in patients with established rheumatoid arthritis (RA) has traditionally been assessed by conventional radiography (CR), which has proven its value in clinical practice and clinical trials over the past decades. The most prominent abnormalities visualized by CR in RA patients are erosions as a consequence of bone destruction and joint space narrowing (JSN) as a consequence of cartilage damage. Several validated scoring systems to quantify the structural joint damage and progression herein are available. Computed tomography and magnetic resonance imaging are newer, more sensitive methods for detection and monitoring of structural joint damage. A validated scoring system for magnetic resonance imaging of the hands and wrists exists, while no consensus has been reached on a scoring system for computed tomography. Structural damage identified by either CR or magnetic resonance imaging predicts a poorer disease course in patients with both early and established rheumatoid arthritis.
29807861 Evaluation of pain intensity in people with rheumatoid arthritis using the MOS intensity s 2019 Aug 2 INTRODUCTION AND OBJECTIVE: Patients with rheumatoid arthritis (RA) consider pain to be their main problem. The goal of this study was to evaluate validity and sensitivity to change to measure pain intensity using the MOS scale in RA patients. PATIENTS AND METHODS: Three hundred sixty-three RA subjects were included. Internal consistency of the instrument was assessed with Chronbach́s alpha, construct validity was estimated with confirmatory factor analysis and hypothesis testing and sensitivity to change was evaluated with the standard response mean and hypothesis testing. RESULTS: The MOS scale showed an appropriate internal consistency (α=0.89) and confirmatory factor analysis revealed it to be a unidimensional scale. In addition, the MOS scale was strongly correlated (rho=0.86) with the visual analogue scale. Convergent validity was demonstrated with the acceptance of 83% of hypotheses a priori. MOS scale standard response mean was 0.33 and 0.21 for the visual analogue scale, pain intensity changes in scales were strongly correlated, supporting its sensitivity to change. CONCLUSION: MOS scale is a useful instrument to measure pain intensity as well as pain relief.
30761753 Real-world effectiveness and safety of rituximab in the treatment of rheumatoid arthritis: 2019 May AIM: To assess the real-world effectiveness and safety of rituximab (RTX) at 24 months in patients with established rheumatoid arthritis (RA) and to identify predictors of low disease activity/remission and a good European League Against Rheumatism (EULAR) response. METHODS: Seventy RTX-treated RA patients were enrolled. Predictors for low disease activity/remission and a good EULAR response at 24 months were identified by multivariate analyses. RESULTS: At 24 months, the mean Disease Activity Score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR) decreased from 6.88 ± 0.85 at baseline to 3.47 ± 0.85. Twenty-nine patients (41.4%) reached low disease activity/remission, while all patients had a moderate/good EULAR response. After adjustment by multivariate analyses, we found concomitant methotrexate at a dosage >10 mg/week (odds ratio [OR] 5.17; 95% CI 1.34-19.93; P = 0.017) predicted low disease activity/remission, and baseline DAS28 ≤6.5 (OR 4.97; 95% CI 1.22-20.30; P = 0.026) predicted good EULAR response at 24 months. The most common adverse events were infusion-related (5.7%), and there was no incidence of malignancy or mortality during the treatment. CONCLUSIONS: RTX was effective and safe in real-life management of RA patients with high disease activity. Patients taking concomitant methotrexate and with lower baseline DAS28-ESR were more likely to benefit from RTX.
31235679 Positive affect as a predictor of adherence in patients with Rheumatoid Arthritis. 2019 Apr The study was conducted in order to investigate adherence in patients with Rheumatoid arthritis (RA), correlating it with other variables such as affect and self-esteem. Seventy-eight patients with RA between 20 and 81 years of age were evaluated. Patients were assessed for Medical Outcomes Study (MOS) Measures of Patient Adherence, Rosenberg self-esteem scale and Short Portuguese version of the Positive and Negative Affect Schedule (PANAS). Pearson's correlation coefficient was used to assess the correlation between the therapeutic compliance and age, disease activity, disability, GPA, self-esteem, affect and inflammatory parameters. An independent T-test was used to evaluate differences in adherence within gender. The one-way analysis of variance (ANOVA) was used to determine associations between adherence and marital status, education level and employment status. A linear regression model was adjusted with stepwise data entry to determine predictors of therapeutic compliance. Patients had a mean age of 57 years and disease duration of 12.8 years. We observed higher levels of adherence in patients with higher self-esteem (r= 0.343, p<0.05) and positive affect (r= 0.345, p<0.01). The adjusted linear regression model allowed the identification of positive affect as a RA patient's adherence predictor (R = 0.347, p<0.05). In our study, high levels of self-reported adherence in RA patients were found. Positive affect seems to be an important determinant of therapeutic adherence in RA patients. These results suggest a relevant role of psychosocial aspects in therapeutic compliance and outcome, which should alert physicians to the need of an holistic approach of the patient.
31823143 Risk factors, including different biologics, associated with depression and anxiety in pat 2020 Mar BACKGROUND: To evaluate the associated factors of depression and anxiety in patients with rheumatoid arthritis (RA) and examine the effect of different biologics. METHODS: This cross-sectional study was conducted in a regional hospital in southern Taiwan from August of 2017 to April of 2018. A total of 625 patients with RA were included. RA disease activity was measured with Disease Activity Score over 28 joints based on erythrocyte sedimentation rate (DAS28-ESR). Depression and anxiety were measured with Hospital Anxiety and Depression Scale (HADS). RESULTS: Based on HADS scores, 38 subjects (6.1%) and 15 subjects (2.4%) were classified as depression and anxiety, respectively. Increased disease activity of RA is noted in RA patients with depression or anxiety, and among the items of DAS28-ESR, only the two subjective components: tender joint count over 28 joints (TJC28) and patient's global assessment (PGA) were significantly different. Multiple logistic regression analysis indicated that depression was significantly associated with TJC28 (adjusted odds ratio [aOR] = 1.10, 95% confidence interval [CI] 1.05-1.14) and female (aOR = 5.43, 95% CI 1.25-23.52); and anxiety was associated with TJC 28 (aOR = 1.07, 95% CI 1.00-1.15) and PGA (aOR = 1.03, 95% CI 1.01-1.06). Secondary analysis found a significantly lower risk of depression (aOR = 0.20, 95% CI 0.04-0.88) in patients receiving etanercept, but not anxiety, when compared with the non-biologic group. CONCLUSIONS: This study suggests that only subjective components of DAS28-ESR were significantly associated with depression and anxiety. In comparison with other biologics, patients receiving etanercept appeared to have a lower risk of depression.Key Points• Rheumatoid arthritis patients possessed higher risk of depression and anxiety.• Both depression and anxiety are strongly correlated with the subjective components of DAS28-ESR.• Etanercept might be the choice of biologics in rheumatoid arthritis patients with depression.
31861764 DNA Damage Response and Oxidative Stress in Systemic Autoimmunity. 2019 Dec 20 The DNA damage response and repair (DDR/R) network, a sum of hierarchically structured signaling pathways that recognize and repair DNA damage, and the immune response to endogenous and/or exogenous threats, act synergistically to enhance cellular defense. On the other hand, a deregulated interplay between these systems underlines inflammatory diseases including malignancies and chronic systemic autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Patients with these diseases are characterized by aberrant immune response to self-antigens with widespread production of autoantibodies and multiple-tissue injury, as well as by the presence of increased oxidative stress. Recent data demonstrate accumulation of endogenous DNA damage in peripheral blood mononuclear cells from these patients, which is related to (a) augmented DNA damage formation, at least partly due to the induction of oxidative stress, and (b) epigenetically regulated functional abnormalities of fundamental DNA repair mechanisms. Because endogenous DNA damage accumulation has serious consequences for cellular health, including genomic instability and enhancement of an aberrant immune response, these results can be exploited for understanding pathogenesis and progression of systemic autoimmune diseases, as well as for the development of new treatments.
31026991 Anti-Inflammatory Effects of Step Electrical Stimulation on Complete Freund's Adjuvant (CF 2019 Oct 1 Rheumatoid arthritis is a chronic inflammatory disease that affects joints and induces pain and swelling. We evaluated the anti-inflammatory effects of step electrical stimulation (SES) in this study. SES was carried out by increasing the voltage (3 V/s) from 5 V to 100 V for 60 cycles. The viability of mouse embryonic fibroblasts (NIH-3T3) was evaluated after step-electrical stimulation. After the injection of complete Freund's adjuvant (CFA) on the right hind paw of Sprague Dawley (SD) rats (6 weeks old), the degree of swelling was measured using a digital plethysmometer and Vernier caliper. Histological changes in inflamed tissues were observed with hematoxylin and eosin (H&E) staining, while the degree of inflammation was evaluated from the expression level of inflammatory factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). As a result, we found no difference in cell viability after SES treatment between the control and SES-treated groups. On day 21 after CFA injection, the swelling of right hind paws decreased by 1.09 times in SES-treated group as compared with the untreated group. In addition, the levels of COX-2, TNF-α and IL-6 significantly decreased after SES treatment. Thus, SES treatment decreased paw swelling and alleviated inflammation.
31435752 Cervical proprioceptive impairment in patients with rheumatoid arthritis. 2019 Dec Rheumatoid arthritis (RA) involving the cervical spine can lead to various neurologic defects and impairment of proprioception is just one of them. The aim of this study was the assessment of cervical proprioception and its relation with radiographic, clinical, and functional characteristics of patients with RA. One hundred and six rheumatoid arthritis patients who diagnosed according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria and age, gender, educational status matched one hundred and six healthy volunteers were enrolled in this study. Cervical joint position error test (CJPET) was applied to healthy volunteers and RA patients for cervical proprioception assessment. Fatigue, depression, balance, quality of life and balance scales were administered to all patients. Cervical radiography was used to assess cervical subluxations. Regression analysis was used for grading the factors which had relations with cervical proprioception. Mean age of patients and healthy volunteers was 51 ± 11.1 and 48.9 ± 9.2, respectively. Scores of CJPET were statistically significantly higher in RA group than healthy volunteers (p = 0.001). CJPET scores were negatively correlated with Berg balance scale findings in right rotation, left rotation, flexion and extension (rho = - 0.421,- 0.473,- 0.448,- 0.515). There was weak or not significant correlation between the scores of CJPET and fatigue, depression, and quality of life scales. Scores of CJPET in patients with atlantoaxial subluxations (AAS) were statistically significantly higher than those without AAS (p < 0.05). Regression analysis results showed that the AAS was related to impaired cervical proprioception on right and left rotations. There was no correlation between CJPET scores and functional parameters. Cervical proprioception impaired in RA patients. This impairment was related to the existence of AAS and balance problems.
30278237 Disease-related outcomes influence prevalence of falls in people with rheumatoid arthritis 2019 Mar BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of falls, with potential adverse outcomes. There is a considerable variation across studies regarding the prevalence of falls and its correlation with clinical data, disease-related outcomes and physical performance tests. OBJECTIVE: The aim of this study was to evaluate the prevalence of falls and its association with clinical data, disease-related outcomes and physical performance tests. METHODS: In this cross-sectional study, 113 RA patients were divided into 3 groups - "non-fallers", "sporadic fallers" and "recurrent fallers" - and compared in terms of clinical data, Clinical Disease Activity Index (CDAI), lower-limb tender and swollen joint count, disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]), Foot Function Index (FFI), Berg Balance Scale (BBS), Timed-up-and-go Test (TUG) and 5-Time Sit Down-To-Stand Up Test (SST5). Logistic regression analysis was performed to analyze the associations between the studied variables and the occurrence of falls, estimating odds ratios (ORs). We also analyzed the correlation between disease outcome measures (HAQ-DI and CDAI) and physical tests (BBS, TUG, SST5). RESULTS: Falls and fear of falling were reported by 59 (52.21%) and 71 (64.5%) patients, respectively. Significant associations were found between "recurrent fallers" and vertigo (OR=3.42; P=0.03), fear of falling (OR=3.44; P=0.01), low income (OR=2.02; P=0.04), CDAI (OR=1.08; P<0.01), HAQ-DI (OR=3.66; P<0.01), Lower-limb HAQ (OR=3.48; P<0.01), FFI-pain (OR=1.24; P=0.03), FFI-total (OR=1.23; P=0.04), lower-limb tender joint count (OR=1.22; P<0.01), BBS score (OR=1.14; P<0.01), TUG score (OR=1.13; P=0.03) and SST5 score (OR=1.06; P=0.02). On multivariate analysis, CDAI was the only significant predictor of recurrent falls (OR=1.08; P<0.01). Physical performance test scores (BBS, TUG, SST5) were correlated with the CDAI and HAQ-DI. CONCLUSION: The prevalence of falls in RA is high, most influenced by disease-related outcomes and linked to worse performance on physical tests (BBS, TUG and SST5).
31602895 [Effect of Tripterygium Glycosides Tablets in treating rheumatoid arthritis:a systematic r 2019 Aug To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.
31059844 Challenges in the treatment of Rheumatoid Arthritis. 2019 Jul Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by a heterogeneous clinical response to the different treatments. Some patients are difficult to treat and do not reach the treatment targets as clinical remission or low disease activity. Known negative prognostic factors, such as the presence of auto-antiantibodies and joint erosion, the presence of a genetic profile, comorbidities and extra-articular manifestations, pregnancy or a pregnancy wish may concur to the treatment failure. In this review we aimed at identify difficult to treat RA patients and define the optimal therapeutic and environmental targets. Genetic markers of severity such as HLA-DRB1, TRAF1, PSORS1C1 and microRNA 146a are differently associated with joint damage; other gene polymorphisms seem to be associated with response to biologic disease modifying anti-rheumatic drugs (bDMARDs). The presence of comorbidities and/or extra-articular manifestations may influence the therapeutic choice; overweight and obese patients are less responsive to TNF inhibitors. In this context the patient profiling can improve the clinical outcome. Targeting different pathways, molecules, and cells involved in the pathogenesis of RA may in part justify the lack response of some patients. An overview of the future therapeutic targets, including bDMARDs (inhibitors of IL-6, GM-CSF, matrix metalloproteinases, chemokines) and targeted synthetic DMARDs (filgotinib, ABT-494, pefacitinib, decernotinib), and environmental targets is addressed. Environmental factors, such as diet and cigarette smoke, may influence susceptibility to autoimmune diseases and interfere with inflammatory pathways. Mediterranean diet, low salt intake, cocoa, curcumin, and physical activity seem to show beneficial effects, however studies of dose finding, safety and efficacy in RA need to be performed.
31461667 The role of registries in the treatment of rheumatoid arthritis with biologic disease-modi 2019 Oct Registries characterize the effectiveness and safety of therapeutic interventions in daily clinical practice. Data from registries enable mining the records of tens of thousands of patients towards determining the effectiveness, safety, and cost-benefit of any given therapeutic. The strengths of registries include real-life settings, greater power than clinical trials to detect rare events, and the study of multiple outcomes and several research questions. Registries also have their weaknesses. They are expensive, less accurate than clinical trials, affected by channelling bias, often require links to external sources or use historic and selected control cohorts or combine datasets to increase power, and have the risk of multiple confounders. Since the beginning of biological era, registries were developed to profile emerging treatments. This article reviews the role of registries in the treatment of rheumatoid arthritis with biologic disease-modifying anti-rheumatic drugs.
31842970 Protein profiling and network enrichment analysis in individuals before and after the onse 2019 Dec 16 BACKGROUND: Antibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses. METHODS: A case-control study was conducted within the Biobank of northern Sweden. The plasma samples from 118 pre-symptomatic individuals (207 samples; median predating time 4.1 years), 79 early RA patients, and 74 matched controls were analyzed. The levels of 122 unique proteins with an acknowledged relationship to autoimmunity were analyzed using 153 antibodies and a bead-based multiplex system (FlexMap3D; Luminex Corp.). The data were analyzed using multifactorial linear regression model, random forest, and network enrichment analysis (NEA) based on the 10 most significantly differentially expressed proteins for each two-by-two group comparison, using the MSigDB collection of hallmarks. RESULTS: There was a high agreement between the different statistical methods to identify the most significant proteins. The adipogenesis and interferon alpha response hallmarks differentiated pre-symptomatic individuals from controls. These two hallmarks included proteins involved in innate immunity. Between pre-symptomatic individuals and RA patients, three hallmarks were identified as follows: apical junction, epithelial mesenchymal transition, and TGF-β signaling, including proteins suggestive of cell interaction, remodulation, and fibrosis. The adipogenesis and heme metabolism hallmarks differentiated RA patients from controls. CONCLUSIONS: We confirm the importance of interferon alpha signaling and lipids in the early phases of RA development. Network enrichment analysis provides a tool for a deeper understanding of molecules involved at different phases of the disease progression.
31739406 miRNAs Regulate Cytokine Secretion Induced by Phosphorylated S100A8/A9 in Neutrophils. 2019 Nov 14 The release of cytokines by neutrophils constitutes an essential process in the development of inflammation by recruiting and activating additional cells. Neutrophils are also able to secrete a complex of S100A8 and S100A9 proteins (S100A8/A9), which can amplify the general inflammatory state of the host and is involved in the pathogenesis of several chronic inflammatory diseases, such as rheumatoid arthritis (RA). S100A8/A9 have received renewed attention due to their susceptibility to several function-altering post-translational modifications. In that context, it has been recently demonstrated that only the phosphorylated form of S100A8/A9 (S100A8/A9-P) is able to induce the secretion of several cytokines in neutrophils. Here, we investigate the mechanism by which this post-translational modification of S100A8/A9 can regulate the extracellular activity of the protein complex and its impact on the inflammatory functions of neutrophils. We found that S100A8/A9-P are present in large amounts in the synovial fluids from RA patients, highlighting the importance of this form of S100A8/A9 complex in the inflammation process. Using miRNA-sequencing on S100A8/A9-P-stimulated differentiated HL-60 cells, we identified a dysregulation of miR-146a-5p and miR-155-5p expression through TRL4 signaling pathways. Our data reveal that overexpression of these miRNAs in neutrophil-like cells reduces S100A8/A9-P-mediated secretion of pro-inflammatory cytokines.
31471142 Autotaxin and chronic inflammatory diseases. 2019 Nov Autotaxin (ATX) is a secreted glycoprotein, widely present in biological fluids including blood. ATX catalyzes the hydrolysis of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a growth factor-like, signaling phospholipid. LPA exerts pleiotropic effects mediated by its G-protein-coupled receptors that are widely expressed and exhibit overlapping specificities. Although ATX also possesses matricellular properties, the majority of ATX reported functions in adulthood are thought to be mediated through the extracellular production of LPA. ATX-mediated LPA synthesis is likely localized at the cell surface through the possible interaction of ATX with integrins or other molecules, while LPA levels are further controlled by a group of membrane-associated lipid-phosphate phosphatases. ATX expression was shown to be necessary for embryonic development, and ATX deficient embryos exhibit defective vascular homeostasis and aberrant neuronal system development. In adult life, ATX is highly expressed in the adipose tissue and has been implicated in diet-induced obesity and glucose homeostasis with multiple implications in metabolic disorders. Additionally, LPA has been shown to affect multiple cell types, including stromal and immune cells in various ways. Therefore, LPA participates in many processes that are intricately involved in the pathogenesis of different chronic inflammatory diseases such as vascular homeostasis, skeletal and stromal remodeling, lymphocyte trafficking and immune regulation. Accordingly, increased ATX and LPA levels have been detected, locally and/or systemically, in patients with chronic inflammatory diseases, most notably idiopathic pulmonary fibrosis (IPF), chronic liver diseases, and rheumatoid arthritis. Genetic and pharmacological studies in mice have confirmed a pathogenetic role for ATX expression and LPA signaling in chronic inflammatory diseases, and provided the proof of principle for therapeutic interventions, as exemplified by the ongoing clinical trials for IPF.
31327821 Gastric Perforation due to Iatrogenic Immunodeficiency-associated Lymphoproliferative Diso 2019 Nov 15 A 71-year-old woman being treated with methotrexate (MTX) and tacrolimus (TAC) for rheumatoid arthritis (RA) was admitted to our hospital and underwent surgery for gastric perforation and peritonitis. An endoscopic examination six days post-surgery showed an extensive ulcer in the stomach, and a biopsy revealed diffused large B-cell lymphoma. We diagnosed her with immunodeficiency-associated lymphoproliferative disorder (LPD) and discontinued the MTX and TAC. She underwent gastrectomy due to stenosis approximately two months after the first operation, but the histopathological findings of lymphoma had disappeared. LPD should be considered as a potential cause of gastric perforation during RA treatment.
30810911 Diagnostic accuracy of anti-keratin antibody for rheumatoid arthritis: a meta-analysis. 2019 Jul OBJECTIVES: Anti-keratin antibody (AKA) is a serum antibody for patients with rheumatoid arthritis (RA), and it has a high specificity. Diagnostic role of AKA in RA was evaluated in this study. METHODS: PubMed, EMBASE, and Web of Science were searched to acquire eligible studies. Articles published before 15 March 2018 were considered to be included. Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the risk of bias and application concern of the included articles. Pooled analysis of diagnostic indicators of AKA for RA was conducted by using a random effects model. Subgroup analysis was employed to explore the potential influencing factors. RevMan 5.3, Stata 11.0, and Meta-DiSc 1.4 software were used in this study. RESULTS: A total of 15 studies (2350 positive and 2067 negative participants) were included. The pooled sensitivity was 0.46 (95% CI 0.44-0.48), pooled specificity was 0.94 (95% CI 0.93-0.95), and pooled diagnostic odds ratio was 15.86 (95% CI 9.48-26.52). In addition, the area under the curve was 0.7194. CONCLUSIONS: The current evidence indicated that AKA has high diagnostic specificity in RA and may be useful for RA diagnostic application in clinic.
31854453 Rheumatoid arthritis research in the 21st century: Limitations of traditional models, new 2020 Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease characterized by progressive bone and cartilage destruction, functional impairment, and long-term disability. Although RA has been described in the medical lit­erature for over two hundred years, its etiology and pathophysiology are insufficiently understood. The current treatment of RA is mainly empirical or based on drugs that interfere with generic steps of the immune response, with limited efficacy and/or significant side effects. Much of RA research has been traditionally based on animals and simplistic in vitro models, which have been shown to poorly recapitulate human RA etiopathogenesis and drug responses. A revolution in science and technology has produced a new generation of more relevant and predictive tools. These tools, which include patient-derived cells, innovative 3D cell culture systems, computational analyses and models, together with omics and large-scale epidemiological studies represent novel and exciting approaches to enhance and forward RA research in a human biology-based perspective. After considering some pitfalls and flaws of traditional models, in this review we discuss novel tools applicable to design human-oriented RA research, while fostering the need for a more holistic and pre­ventative approach to the disease. Our goal is to stimulate discussion, both at scientific and public level, on the need to explore new avenues in RA research and to support a paradigm-shift from animal-based towards human biology-based systems to better understand human pathophysiology and to develop more effective targeted therapies for personalized treatment and prevention.
31338093 Candidate Markers for Stratification and Classification in Rheumatoid Arthritis. 2019 Rheumatoid arthritis (RA) is a chronic autoimmune, inflammatory disease, characterized by synovitis in small- and medium-sized joints and, if not treated early and efficiently, joint damage, and destruction. RA is a heterogeneous disease with a plethora of treatment options. The pro-inflammatory cytokine tumor necrosis factor (TNF) plays a central role in the pathogenesis of RA, and TNF inhibitors effectively repress inflammatory activity in RA. Currently, treatment decisions are primarily based on empirics and economic considerations. However, the considerable interpatient variability in response to treatment is a challenge. Markers for a more exact patient classification and stratification are lacking. The objective of this study was to identify markers in immune cell populations that distinguish RA patients from healthy donors with an emphasis on TNF signaling. We employed mass cytometry (CyTOF) with a panel of 13 phenotyping and 10 functional markers to explore signaling in unstimulated and TNF-stimulated peripheral blood mononuclear cells from 20 newly diagnosed, untreated RA patients and 20 healthy donors. The resulting high-dimensional data were analyzed in three independent analysis pipelines, characterized by differences in both data clean-up, identification of cell subsets/clustering and statistical approaches. All three analysis pipelines identified p-p38, IkBa, p-cJun, p-NFkB, and CD86 in cells of both the innate arm (myeloid dendritic cells and classical monocytes) and the adaptive arm (memory CD4(+) T cells) of the immune system as markers for differentiation between RA patients and healthy donors. Inclusion of the markers p-Akt and CD120b resulted in the correct classification of 18 of 20 RA patients and 17 of 20 healthy donors in regression modeling based on a combined model of basal and TNF-induced signal. Expression patterns in a set of functional markers and specific immune cell subsets were distinct in RA patients compared to healthy individuals. These signatures may support studies of disease pathogenesis, provide candidate markers for response, and non-response to TNF inhibitor treatment, and aid the identification of future therapeutic targets.
31211506 Comparison of the efficacy and safety of tofacitinib and upadacitinib in patients with act 2019 Aug OBJECTIVES: The relative efficacy and safety of tofacitinib and upadacitinib were assessed in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic (cs) or biologic (b) disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib and upadacitinib in combination with methotrexate (MTX) in RA patients with an inadequate cs- or b-DMARD response. RESULTS: Nine RCTs including 5794 patients met the inclusion criteria. There were 15 pairwise comparisons including 10 direct comparisons of 6 interventions. Upadacitinib 15 mg + MTX and upadacitinib 30 mg + MTX were among the most effective treatments for active RA with an inadequate cs- or b-DMARD response, followed by tofacitinib 10 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab + MTX. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX and upadacitinib 30 mg + MTX had the highest probability of being the best treatment in terms of the American College of Rheumatology 20 response rate (SUCRA = 0.820, 0.762), followed by tofacitinib 10 mg + MTX (SUCRA = 0.623), tofacitinib 5 mg + MTX (SUCRA = 0.424), adalimumab + MTX (SUCRA = 0.371), and placebo + MTX (SUCRA = 0.001). No significant differences were observed in the incidence of serious adverse events after treatment with tofacitinib + MTX, upadacitinib + MTX, adalimumab + MTX, or placebo + MTX. CONCLUSIONS: In RA patients with an inadequate response to cs- or b-DMARDs, upadacitinib 15 mg + MTX and upadacitinib 30 mg + MTX were the most efficacious interventions and were not associated with significant risks of serious adverse events.