Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
29781581 Brain Correlates of Continuous Pain in Rheumatoid Arthritis as Measured by Pulsed Arterial 2019 Feb OBJECTIVE: Central nervous system pathways involving pain modulation shape the pain experience in patients with chronic pain. The aims of this study were to understand the mechanisms underlying pain in patients with rheumatoid arthritis (RA) and to identify brain signals that may serve as imaging markers for developing targeted treatments for RA-related pain. METHODS: Patients with RA and matched control subjects underwent functional magnetic resonance imaging, using pulsed arterial spin labeling. The imaging conditions included 1) resting state, 2) low-intensity stimulus, and 3) high-intensity stimulus. Stimuli consisted of mechanical pressure applied to metacarpophalangeal (MCP) joints with an automated cuff inflator. The low-intensity stimulus was inflation to 30 mm Hg. The high-intensity stimulus was the amount of pressure required to achieve a pain intensity rating of 40 on a 100-point scale for each RA patient, with the same amount of pressure used in the matched control. RESULTS: Among RA patients, regional cerebral blood flow (rCBF) in the medial frontal cortex and dorsolateral prefrontal cortex increased during both low-pressure and high-pressure stimulation. No rCBF changes were observed in pain-free controls. Region-of-interest analyses in RA patients showed that baseline rCBF in the medial frontal cortex was negatively correlated with the pressure required for the high-intensity stimulus and positively correlated with pain induced by the low-intensity stimulus. Baseline rCBF was also marginally correlated with disease activity). Regional CBF during high pain was positively correlated with pain severity and pain interference. CONCLUSION: In response to clinically relevant joint pain evoked by pressure applied to the MCP joint, neural processing in the medial frontal cortex increases and is directly associated with clinical pain in patients with RA.
31287314 Synthesis and Evaluation of Carbonic Anhydrase Inhibitors with Carbon Monoxide Releasing P 2019 Aug 8 Carbon monoxide (CO) is a gas endogenously produced in humans, reported to exhibit anti-inflammatory and cytoprotective effects at low concentration. In this context, CO releasing molecules (CORMs) are attracting enormous interest. Herein, we report a series of small-molecule hybrids consisting of a carbonic anhydrase (CA; EC 4.2.1.1) inhibitor linked to a CORM tail section (CAI-CORMs). All compounds were screened in vitro for their inhibition activity against the human (h) CA I, II, IV, IX, and XII isoforms. On selected CAI-CORM hybrids, the CO releasing properties were evaluated, along with their pain-relieving effect, in a model of rheumatoid arthritis. One CAI-CORM hybrid (5b) induced a higher pain-relieving effect compared to the one exerted by the single administration of CAI (5a) and CORM (15b) fragments, shedding light on the possibility to enhance the pain relief effect of CA inhibitors inserting a CO releasing moiety on the same molecular scaffold.
30073771 Comparison of outpatient reimbursement for interstitial cystitis/bladder pain syndrome and 2019 Apr OBJECTIVE: This study compared Taiwanese public health insurance outpatient reimbursements for interstitial cystitis (IC)/bladder pain syndrome (BPS) and rheumatoid arthritis (RA) treatment. METHODS: This observational study used data from the Taiwan Longitudinal Health Insurance Database between 2002 and 2013. Patients with International Classification of Diseases, Ninth Revision, Clinical Modification codes for IC/BPS and RA were selected and matched in a ratio of 1 : 5 based on index year. After adjustment for possible confounders, including age, sex, income, hospital levels of care, and reimbursements for 24 comorbidities, yearly and per-visit pharmacy, non-pharmacy, and total claims were determined. RESULTS: In all, 1438 IC/BPS and 7190 RA patients were identified in the database. IC/BPS patients were significantly younger, and the proportion of females in this group was higher. Income levels were lower in the IC/BPS cohort, but not significantly. There were no significant differences between cohorts in terms of reimbursements for treatment for comorbidities, with the exception of end-stage renal disease, for which reimbursement was higher in the RA cohort. After adjusting for confounders, the regression coefficient for IC/BPS to RA was significantly lower for yearly total pharmacy claims, yearly total claims, per-visit pharmacy claims, and total claims per visit. CONCLUSIONS: Outpatient reimbursement was significantly lower for IC/BPS than for RA treatment, primarily with regard to pharmacy costs. This indicates less medical utilization for IC/BPS, possibly due to poor treatment outcomes and copayment polices. Further advances in the treatment of IC/BPS and health budget reallocation are encouraged.
31856612 Effects of guluronic acid, as a new NSAID with immunomodulatory properties on IL-17, RORγ 2020 Feb Aim: Rheumatoid arthritis (RA) is a prevalent inflammatory, autoimmune diseases characterized by inflammation and destruction of joints. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can have modulatory interference in disease process. In this study, the effect of Guluronic Acid (G2013) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunomodulatory effects was evaluated on IL-17, RORγt, IL-4 and GATA-3 gene expression in RA patients.Methods: Fourteen patients with RA who had an inadequate response to conventional treatments were included in this clinical trial. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. G2013 was administered orally at dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the gene expression levels of IL-4, GATA-3, IL-17 and RORγt.Results: Primary and secondary efficacy endpoints and Disease Activity Score (DAS) 28 showed an improvement after 12 weeks of treatment. G2013 has a potent efficacy on gene expression of these molecules, so that it could decrease IL-17 and RORγt levels and increase IL-4 and GATA-3 levels after 12 weeks of treatment. Reduction of IL-17 was statistically non-significant whereas for its transcription factor (RORγt) was statistically significant. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments.Conclusion: G2013 as a natural novel drug showed a significant increase on IL-4 and GATA-3 and a significant decrease on RORγt gene expression after 12 weeks oral administration of this drug in RA patients. (Clinical trial identifier: IRCT2016092813739N5).
31350056 Different risk profiles of biologic agents for new-onset psoriasis in patients with rheuma 2020 Feb OBJECTIVE: To investigate rates and risk factors for incident and recurrent psoriasis in rheumatoid arthritis (RA) patients treated with different biologic (b) and conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs). METHODS: RA patients enrolled in the German biologics register RABBIT without (n = 14,525) or with a history of psoriasis (n = 375) were analyzed separately. All first events of psoriasis reported until October 2017 were assigned to the treatments prescribed in the previous 3 months. Crude incidence rates (IR) of psoriasis were calculated per 1000 patient-years. To investigate risk factors for psoriasis, cox regressions with and without inverse probability weights were applied to adjust for confounding by indication. RESULTS: 117 incident and 37 recurrent psoriatic events were reported. Patients exposed to TNFi had a significantly higher incidence rate (IR = 3.04/1,000 PY) than those exposed to csDMARDs only (IR = 0.65), whereas IRs for abatacept, rituximab and tocilizumab did not differ significantly from csDMARDs. Adjusted Cox regression confirmed a higher risk for TNFi. Female sex (HR: 1.7) and smoking (HR: 2.1) were significantly associated with incident psoriasis while methotrexate decreased the risk (HR: 0.5). For recurrent psoriasis, IRs for TNFi, abatacept and rituximab were significantly higher than for csDMARDs. CONCLUSIONS: Our data confirm a previously observed increased risk of incident psoriasis in patients exposed to TNFi compared to csDMARDs. However, the overall risk is low and the event is usually non-serious. Comedication of TNFi with methotrexate seems to lower the risk of incident psoriasis. In patients with a history of psoriasis, recurrence as adverse event is rare.
30912120 Downregulated microRNA-135a ameliorates rheumatoid arthritis by inactivation of the phosph 2019 Aug Synovial fibroblasts (SFs) of rheumatoid arthritis (RA) are phenotypically aggressive, typically progressing into arthritic cartilage degradation. Throughout our study, we made explorations into the effects of microRNA-135a (miR-135a) on the SFs involved in RA by mediating the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway via regulation of phosphatidylinositol 3-kinase regulatory subunit 2 (PIK3R2). The expression of PI3K was higher, the expression of PIK3R2 was lower, and AKT was phosphorylated in the RA synovial tissues, relative to the levels found in the normal synovial tissues. We predicted miR-135a to be a candidate miR targeting PIK3R2 using an online website, microRNA.org, which was verified with a dual-luciferase reporter gene assay. Subsequently, high miR-135a expression was observed in RA synovial tissues. To study the effect of the interaction between miR-135a and PIK3R2 in RA, the SFs isolated from RA samples were cultured and transfected with mimic, inhibitor, and small interfering RNA. The proliferation, invasion, and apoptosis of the SFs were detected after the transfection. The cells transfected with miR-135a inhibitor showed inhibited cell proliferation, migration, and invasion, while also displaying promoted cell apoptosis, G0/G1 cell ratio, and decreased S cell ratio, through upregulation of PIK3R2 and inactivation of the PI3K/AKT signaling pathway. These findings provided evidence that downregulation of miR-135a inhibits proliferation, migration, and invasion and promotes apoptosis of SFs in RA by upregulating the PIK3R2 coupled with inactivating the PI3K/AKT signaling pathway. The downregulation of miR-135a might be a potential target in the treatment of RA.
31872724 [Nanometer preparation of traditional Chinese medicine for rheumatoid arthritis]. 2019 Sep Rheumatoid arthritis( RA) is a chronic autoimmune disease,which can occur at any age. Repeated severe attacks can cause joint deformities. Its pathogenesis is complex,and the pathophysiological process involves many different types of cells. At present,the pathogenesis of RA is still unclear,and the clinical medication mainly aims to alleviate inflammation and symptoms.DMARDs,non-steroidal anti-inflammatory drugs,adrenocortical hormones,biological agents and traditional Chinese medicine are all applied in clinic. Traditional Chinese medicine has a long history in the treatment of RA. In particular,traditional Chinese medicine compounds can treat RA through multiple target points. The combination of nanotechnology and anti-inflammatory traditional Chinese and western medicines has also attracted extensive attention. Nanotechnology can selectively deliver drugs to articular cavity by taking advantage of its small carrier size and biodegradable materials. It can reduce the size of drug delivered,and increase the accuracy,safety and effectiveness of drugs,and further improve the therapeutic efficacy of drugs on RA. In this paper,traditional Chinese and western medicines and their nano-preparations used in the treatment of RA were reviewed in the past five years. The researches of nano-preparation were discussed in terms of pharmacology category. This paper provided reference for the research and development of new-type nano-preparation with outstanding clinical efficacy.
31810550 Suspected very early inflammatory rheumatic diseases in primary care. 2019 Aug As primary care clinicians are typically the first point of contact for patients with musculoskeletal problems, they are crucial to the early diagnosis and treatment of patients with an incident inflammatory arthritis, like rheumatoid arthritis. Current UK and international guidelines recognise this, recommending the prompt referral of patients with suspected persistent synovitis to secondary care. In England and Wales, this is advised to occur within 3 working days. However, recent audit data suggests this recommendation is infrequently met, with some patients waiting many months for referral. In this review article we will discuss the various challenges to achieving the early referral of patients with a new-onset inflammatory arthritis from primary to secondary care. We will also describe how these challenges could potentially be overcome, with the ultimate goal of ensuring that the right patients are referred to the right services, and at the right time.
29532734 Efficacy and safety of sirukumab in Japanese patients with active rheumatoid arthritis who 2019 Mar OBJECTIVE: To evaluate the efficacy and safety of sirukumab, a human anti-interleukin six monoclonal antibody, in Japanese patients with rheumatoid arthritis who were refractory to anti-tumor necrosis factor therapy. METHODS: This subgroup analysis, based on a double-blind, placebo-controlled, 52-week phase 3, global study (SIRROUND-T) assessed the American College of Rheumatology (ACR) 20 response at week 16 (primary endpoint). Secondary endpoints: ACR 50, Disease Activity Score in 28 joints-C reactive protein, Health Assessment Questionnaire-Disability Index and safety were assessed. Results 116/878 patients received sirukumab 50 mg/4 weeks (q4w, n = 35), 100 mg/2 weeks (q2w, n = 44) or placebo (n = 37) subcutaneously. Significantly more patients achieved ACR 20 response at week 16 with sirukumab (50 mg q4w:20 [57.1%]; p < .001, 100 mg q2w:24 [54.5%]; p = .001) versus placebo (7 [18.9%]); consistent significant improvement in secondary endpoints at week 24 and 52 was observed. At week 24, incidence of treatment-emergent adverse events (TEAEs) was numerically higher with sirukumab groups (50 mg q4w:29 [82.9%]; 100 mg q2w:38 [86.4%] versus placebo (28 [75.7%]); however, at week 52, sirukumab combined groups had comparable incidence of TEAEs. CONCLUSION: Efficacy findings through 52 weeks were comparable between sirukumab doses in Japanese patients and consistent with primary SIRROUND-T study results. No new safety signals were observed.
31522386 Detecting joints with erosion(s) in rheumatoid arthritis: a novel individualized-ultrasoun 2019 Nov PURPOSE: To determine if a novel individualized-ultrasound (IUS) method can detect more joints with erosion(s) in rheumatoid arthritis (RA) patients versus existing methods. MATERIALS AND METHODS: The IUS method selects up to 7 or 14 ultrasonographically most inflamed joints whereas existing methods pre-fix 7 or 14 joints for ultrasonography. Using ultrasonography, the mean total inflammatory score (TIS), mean number of affected joints and mean number of joints with erosion(s) were compared between novel and existing methods among 30 RA patients using the paired Student t test. RESULTS: Using 7-joint approach, comparing IUS versus existing methods, the mean (95% CI) for TIS, number of affected joints, and number of joints with erosion(s) were: 2.18 (1.88, 2.48) versus 0.95 (0.78, 1.11); 7 (7, 7) versus 4.43 (3.93, 4.94); 3.20 (2.44, 3.96) versus 1.33 (0.94, 1.72), respectively. Using 14-joint approach, comparing IUS versus existing methods, the mean (95% CI) for TIS, number of affected joints, and number of joints with erosion(s) were: 3.17 (2.75, 3.6) versus 1.71 (1.38, 2.04); 13.5 (13.05, 13.95) versus 8.13 (7.24, 9.02); 4.23 (3.13, 5.34) versus 2.77 (2.03, 3.50), respectively. p values all < 0.0001. CONCLUSIONS: A novel IUS method detects substantially more joints with erosion(s) in RA patients versus existing methods.
30318125 Keeping physically active with rheumatoid arthritis: semi-structured interviews to explore 2019 Sep BACKGROUND: Regular physical activity is safe and beneficial for people with rheumatoid arthritis (RA) but the majority of people with RA are less active than the general population and have a higher risk of co-morbidities. Exploring strategies used by physically active people with RA could inform effective methods to support those who are less active. OBJECTIVE: To explore the perspectives, experiences and strategies employed by people with RA who successfully engage with regular physical activity. DESIGN: Individual semi-structured interviews and thematic analysis. PARTICIPANTS: A purposive sample of physically active people with RA. RESULTS: Twelve females and three males participated (mean age 56, range 29 to 80; mean disease duration 13 years, range 10 months to 46 years). Analysis revealed eight constructs clustered into three themes. Theme 1: 'the individual' incorporated constructs of symptoms, feelings and role; theme 2: 'management' incorporated medical and self-management; theme 3: 'physical activity' incorporated constructs of type of physical activity, including barriers or facilitators. Participants reported a long history of physical activity prior to diagnosis and good support networks. All participants recognised that physical activity was key to their RA management, acknowledged the benefits from engaging in physical activity and were able to overcome barriers. Participants had strong beliefs that physical function would decline without regular physical activity. CONCLUSIONS: People with RA who successfully maintain physical activity are motivated by a desire to manage symptoms, resist functional decline and maintain health and independence. These findings should be explored with a wider range of people with RA.
31148565 Periodontal treatment prevents arthritis in mice and methotrexate ameliorates periodontal 2019 May 31 Recent studies indicate a causal relationship between the periodontal pathogen P. gingivalis and rheumatoid arthritis involving the production of autoantibodies against citrullinated peptides. We therefore postulated that therapeutic eradication P. gingivalis may ameliorate rheumatoid arthritis development and here turned to a mouse model in order to challenge our hypothesis. F1 (DBA/1 x B10.Q) mice were orally inoculated with P. gingivalis before collagen-induced arthritis was provoked. Chlorhexidine or metronidazole were orally administered either before or during the induction phase of arthritis and their effects on arthritis progression and alveolar bone loss were compared to intraperitoneally injected methotrexate. Arthritis incidence and severity were macroscopically scored and alveolar bone loss was evaluated via microcomputed tomography. Serum antibody titres against P. gingivalis were quantified by ELISA and microbial dysbiosis following oral inoculation was monitored in stool samples via microbiome analyses. Both, oral chlorhexidine and metronidazole reduced the incidence and ameliorated the severity of collagen-induced arthritis comparable to methotrexate. Likewise, all three therapies attenuated alveolar bone loss. Relative abundance of Porphyromonadaceae was increased after oral inoculation with P. gingivalis and decreased after treatment. This is the first study to describe beneficial effects of non-surgical periodontal treatment on collagen-induced arthritis in mice and suggests that mouthwash with chlorhexidine or metronidazole may also be beneficial for patients with rheumatoid arthritis and a coexisting periodontitis. Methotrexate ameliorated periodontitis in mice, further raising the possibility that methotrexate may also positively impact on the tooth supporting tissues of patients with rheumatoid arthritis.
31339961 Cost-effectiveness of abatacept, tocilizumab and TNF-inhibitors compared with rituximab as 2019 OBJECTIVES: The objective of this study was to evaluate the cost-effectiveness of abatacept, tocilizumab, and tumor necrosis factor (TNF) inhibitors as compared with rituximab in Finnish rheumatoid arthritis patients, who have previously been treated with TNF inhibitors. METHODS: A patient-level simulation model was developed to predict costs and outcomes associated with four biological drugs (abatacept, tocilizumab, rituximab and TNF inhibitors) in the treatment of rheumatoid arthritis. Following lack of efficacy or adverse events, the patients were switched to another biological drug until all four options were exhausted. After that, the patients were assumed to receive a 6th line treatment until death. The patients' baseline characteristics and regression models used in the simulation were based on observational data from the National Register for Biological Treatments in Finland. Direct costs comprised drug costs, administration costs, costs of switching, and outpatient and inpatient care, while indirect costs included disability pension and sick leaves due to rheumatoid arthritis. Several subgroup and deterministic sensitivity analyses were conducted. RESULTS: Drug costs were the lowest for rituximab, but when administration costs and costs of switching were included, drug costs were the lowest for TNF inhibitors. Abatacept was associated with the highest drug costs, whereas rituximab was associated with the highest healthcare costs. In total, TNF inhibitors had the lowest direct costs, while rituximab had the highest direct costs. The amount of quality-adjusted life years (QALY) gained ranged from 9.405 for rituximab to 9.661 for TNF inhibitors. TNF inhibitors, abatacept, and tocilizumab were dominant in comparison to RTX. CONCLUSIONS: TNF inhibitors, abatacept, and tocilizumab had lower costs and higher QALYs than rituximab, and therefore, they were dominant in comparison to rituximab. As TNF inhibitors had the lowest costs and highest QALYs, they were the most cost-effective treatment option.
30834699 microRNA involvement in the regulation of survivin in peripheral blood mononuclear cells f 2019 Jun AIM: Impaired regulation of immune tolerance results in autoimmune diseases, such as rheumatoid arthritis (RA). Survivin is an anti-apoptotic protein and can induce cellular mitosis. In the current study, we assessed the transcript level of total survivin (survivin-TS) and its three major variants and evaluated the expression level of important micro RNAs (miRNAs) involved in survivin expression regulation in RA patients. METHOD: Peripheral blood mononuclear cells (PBMCs) were isolated from 50 healthy controls and 50 RA-active patients. RNA extraction was performed and then single-strand complementary DNA was synthesized. Quantitative real-time polymerase chain reaction was used to assess the expression level of survivin-TS and its variants with effective miRNAs in PBMCs. RESULTS: Overexpression of survivin-2B (fold change = 1.57, P = 0.005), survivn-ΔEx3 (fold change = 1.93, P = 0.009) and downregulation of survivin-WT (fold change = 0.64, P = 0.0002) were found in PBMCs of patients, while messenger RNA (mRNA) expression of survivin-TS had no significant difference between RA patients and controls. Expression levels of miR-335-5p, miR-485-5p, miR-16-5p, miR-150-5p, miR-34a-5p, and miR-203a-3p were significantly increased in PBMCs from patients compared with healthy controls. In a correlation study, dysregulation of these miRNAs were not correlated with mRNA expression level of survivin. CONCLUSION: While survivin-TS was not differently expressed in RA patients, its variants had altered expression. Although miRNAs were aberrantly expressed in PBMCs from RA subjects, they did not regulate survivin-TS. miRNAs might be involved in RA pathogenesis, but not through controlling survivin.
30173156 High Burden of Sexual Dysfunction in Female Patients with Rheumatoid Arthritis: Results of 2019 Jan OBJECTIVE: To evaluate the effect of rheumatoid arthritis (RA) on impairing women's sexuality regarding motivation, activity, and satisfaction, and to assess the correlation of disease-related physical impairment within sexual functioning. METHODS: An anonymous survey among women with RA and healthy controls (HC) using standardized questionnaires, predominantly the Changes in Sexual Functioning Questionnaire-short form (CSFQ-14). In addition, disease activity, depression, and disability were evaluated. RESULTS: There were 319 questionnaires distributed to patients and 306 to HC. Of these, 235 patient questionnaires (73.7%) and 180 HC questionnaires (58.8%) were returned, of which 203 and 169 were completed, respectively. Of the patients with RA, 47.8% had a total CSFQ-14 score of ≤ 41, indicating female sexual dysfunction (FSD), as compared to 14.2% of HC (p < 0.0001). The median CSFQ-14 score was lower in patients with RA [42 points, interquartile range (IQR) 36-48] than in HC (49 points, IQR 44-54; p < 0.0001), resulting in an OR of 5.53 (95% CI 3.19-9.57; p < 0.0001). After adjustment for confounders, given a higher mean age of patients (55.2 ± 11.3 yrs) than HC (47.4 ± 11.8 yrs; p < 0.0001), the OR for FSD in patients with RA was still 3.04 (95% CI 1.61-5.75; p = 0.001). Neither the Health Assessment Questionnaire-Disability Index nor the Clinical Disease Activity Index was associated with FSD after adjustment. CONCLUSION: FSD apparently is highly prevalent in female patients with RA, affects all subdomains of sexual function, and is most likely underestimated in daily clinical practice. Of note, FSD could not be linked to disability or RA disease activity.
30647173 The 2018 OMERACT Synovial Tissue Biopsy Special Interest Group Report on Standardization o 2019 Oct OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) synovial tissue biopsy (STB) working group initiated an international effort to standardize STB analyses, define consensual items to inform treatment choices, and predict responses in rheumatoid arthritis (RA). METHODS: (1) A Delphi survey to determine items for STB analyses. (2) A multicenter retrospective study of STB data in patients with RA posttreatment with biological disease-modifying antirheumatic drugs. RESULTS: The Delphi survey identified 18 STB analyses items. Consensus on histological markers was achieved in the OMERACT 2018 SIG. CONCLUSION: Six markers were identified for examination in a multicenter study designed to define an OMERACT-endorsed set of STB markers to predict responses to treatment.
30628539 Validation of a clinical pharmacogenetic model to predict methotrexate nonresponse in rheu 2019 Jan AIM: To study the performance of a clinical pharmacogenetic model for the prediction of nonresponse in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) in combination with other synthetic or biologic disease-modifying anti-rheumatic drugs . This prediction model includes gender, smoking status, rheumatoid factor positivity and four genetic variants in AMPD1 (rs17602729), ATIC (rs2372536), ITPA (rs1127354) and MTHFD1 (rs17850560). METHODS: A total of 314 RA patients from three Dutch studies were retrospectively included. Eligible patients were adults diagnosed with RA and had a treatment duration with MTX and follow-up for at least two study evaluation visits. Prediction model risk scores at the first and second evaluation were calculated and compared with the actual nonresponse (disease activity score >2.4). Regression and receiver operating characteristic curve analyses of the prediction model were performed. Also, the sensitivity, specificity and the positive and negative predictive values (PPV and NPV) were determined. RESULTS: The receiver operating characteristic area under the curve was 75% at first and 70% after second evaluation. At the second evaluation, prediction nonresponse had a sensitivity of 67% (CI: 54-78%), specificity of 69% (CI: 60-77%), PPV of 52% (CI: 45-60%) and NPV of 80% (CI: 73-85%). CONCLUSIONS: This study demonstrates that the clinical pharmacogenetic model has an inadequate performance for the prediction of nonresponse to MTX in RA patients treated with combination therapies.
31261500 Correlation of fatigue with other disease related and psychosocial factors in patients wit 2019 Jun To assess the hypothesis if tocilizumab (TCZ) is effective on disease activity, and also its effect in fatigue and other clinical and psychological disease-related factors in patients with rheumatoid arthritis (RA) treated with TCZ.A 24-week, multicenter, prospective, observational study in patients with moderate to severe RA receiving TCZ after failure or intolerance to disease-modifying antirheumatic drugs or tumor necrosis factor-alpha was conducted.Of the 122 patients included, 85 were evaluable for effectiveness (85% female, 51.9 ± 12.5 years, disease duration 8.7 ± 7.4 years). Mean change in C-reactive protein level from baseline to week 12 was -11.2 ± 4.0 (P < .001). Mean Disease Activity Index score (DAS28) decreased from 5.5 ± 1.0 at baseline to 2.7 ± 1.3 (P < .001) at week 24. Mean change in Functional Assessment of Chronic Illness Therapy score was -5.4 ± 11.2 points at week 24. Multiple regression analysis showed that the improvement in DAS28, sleep, and depression explained 56% and 47% of fatigue variance at week 12 and 24, respectively.Tocilizumab is effective in reducing disease activity and results in a clinically significant improvement in fatigue, pain, swollen joint count, morning stiffness, sleepiness, depression, and DAS28; the last 3 were specifically identified as factors explaining fatigue variance with the use of TCZ in RA patients.
31537249 [Up-expression of ICOS and PD-1 on peripheral CD3(+)CD8(+) effector memory T cells and Tfh 2019 Jul Objective To investigate the expression of programmed cell death 1 (PD-1) and inducible costimulatory molecules (ICOS) on peripheral T lymphocytes of patients with rheumatoid arthritis (RA) and to determine its relationship with disease severity. Methods The study included 30 RA patients and 26 healthy people. Flow cytometry was used to detect the ratio of CD3(+)CD8(+) effector memory T cells (Tem) and follicular helper T (Tfh) cells in peripheral blood, and then to detect the proportion of PD-1 and ICOS-positive cells in lymphocyte subsets. Correlation between them and 28 joint disease activity scores (DAS28) was assessed by Spearman correlation analysis. Results The absolute number of Tem and Tfh cells in the RA group was higher than that in the healthy group. The expression of ICOS and PD-1 in the RA group was higher than that in the healthy group. There was a positive correlation between the expression of ICOS and PD-1 on peripheral CD3(+)CD8(+) Tem and Tfh cells and DAS28 in RA group. Conclusion PD-1 and ICOS on peripheral CD3(+)CD8(+) Tem and Tfh cells may be involved in the development of RA and may be an indicator of RA activity.
30844558 The effect of non-TNF-targeted biologics on vascular dysfunction in rheumatoid arthritis: 2019 May BACKGROUND: Rheumatoid arthritis (RA) is burdened by a significant increase in cardiovascular disease (CVD) risk. Amongst CVD risk factors, endothelial dysfunction and arterial stiffness represent powerful predictors of atherosclerosis and cardiovascular events in the general population and in RA patients. METHODS: A systematic review of the literature was performed to identify the available data on the effect of non-TNF-targeted biologics licensed for the treatment of RA on endothelial function, arterial stiffness or subclinical atherosclerosis. MedLine (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science (WOS) databases were searched using a predefined strategy to identify relevant articles. RESULTS: The search strategy initially retrieved 389 records. After screening titles and abstracts, a total of 362 studies were excluded. Amongst the remaining 27 studies selected for final examination, 16 articles were included in the systematic literature review. Included studies demonstrated a significant effect of abatacept, anakinra, rituximab and tocilizumab in improving endothelial dysfunction associated with RA; the effect on arterial stiffness was less consistent and deserves further investigation. No significant effect of non-TNF-targeted biologics was observed for measures of subclinical atherosclerosis. CONCLUSION: Non-TNF-targeted biologics have been associated with favorable effects on endothelial dysfunction as already demonstrated for TNF inhibitors. Future studies are needed to ascertain the impact of this mediations on arterial stiffness in RA patients.