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ID PMID Title PublicationDate abstract
33087182 CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial f 2020 Oct 21 BACKGROUND: Osteoarthritis (OA) and rheumatoid arthritis (RA) are common joint disorders that are considered to be different diseases due to their unique molecular mechanisms and pathogenesis. Chemokines and their corresponding receptors have been well characterized in RA progression, but less so in OA pathogenesis. METHODS: The human primary synovial fibroblasts (SFs) were obtained from human OA and RA tissue samples. The Western blot and qPCR were performed to analyze the expression levels of CXCL1, as well as CXCL-promoted IL-6 expression in both OASFs and RASFs. The signal cascades that mediate the CXCL1-promoted IL-6 expression were identified by using chemical inhibitors, siRNAs, and shRNAs. RESULTS: Here, we found that both diseases feature elevated levels of CXCL1 and interleukin (IL)-6, an important proinflammatory cytokine that participates in OA and RA pathogenesis. In OASFs and RASFs, CXCL1 promoted IL-6 expression in a dose- and time-dependent manner. In OASFs and RASFs overexpressing CXCL1 or transduced with shRNA plasmid, IL-6 expression was markedly upregulated. CXCR2, c-Raf, and MAPKs were found to regulate CXCL1-induced IL-6 expression in OASFs and RASFs. Finally, CXCL1 triggered the transcriptional activities of c-Jun (which regulates the expression of proinflammatory proteins) in OASFs and RASFs. CONCLUSIONS: Our present work suggests that the CXCL1/CXCR2 axis helps to orchestrate inflammatory responses in OA and RA SFs.
31203231 Orthopedic Surgery in Rheumatoid Arthritis: Results from the Spanish National Registry of 2020 Mar OBJECTIVE: To analyze the trend of orthopedic surgery (OS) rates on patients with rheumatoid arthritis (RA). METHODS: Retrospective observational study based on information provided by the Spanish National System of Hospital Data Surveillance. All hospitalizations of patients with RA for orthopedic surgery [total hip arthroplasty (THA), total knee arthroplasty (TKA), arthrodesis, and upper limb arthroplasty (ULA)] during 1999-2015 were analyzed. The age-adjusted rate was calculated. Generalized linear models were used for trend analysis. RESULTS: There were 21,088 OS in patients over 20 years of age (77.9% women). OS rate adjusted by age was 754.63/100,000 RA patients/year (women 707.4, men 861.1). Neither an increasing nor a decreasing trend was noted for the total OS. However, trend and age interacted, so in the age ranges 20-40 years and 40-60 years, an annual reduction of 2.69% and 2.97%, respectively, was noted. In the age ranges over 80 years and 60-80 years, we noted an annual increase of 5.40% and 1.09%, respectively. The average age at time of OS increased 5.5 years during the period analyzed. For specific surgeries, a global annual reduction was noted in rates for arthrodesis. In THA, there was an annual reduction in patients under 80 years. In TKA and ULA, there was an annual reduction in patients under 60 years. CONCLUSION: Although the overall OS rate has not changed, there is a decrease in the rate of arthrodesis at all ages, THA in patients under 80 years of age, as well as TKA and ULA in patients under 60 years of age.
31774612 Patients and relatives coping with inflammatory arthritis: Care teamwork. 2020 Feb OBJECTIVE: To explore how patients and relatives experience and talk together about their life with inflammatory arthritis. DESIGN: Qualitative research. SETTING: A convenience sample was used. Participants were recruited in seven rheumatology departments in France. PARTICIPANTS: Patients with rheumatoid arthritis or spondyloarthritis, agreeing to participate in the study with a relative, age at least 18 years. DATA COLLECTION AND ANALYSIS: Two psychologists conducted face-to-face interviews with 20 patient-relative dyads (40 individuals). A thematic analysis followed a general inductive approach. RESULTS: Saturation was reached after interviews with 20 dyads. The analysis revealed four main themes: (a) disease 'lived' together: a new role for the relative (providing help in physical tasks, emotional support, acting as a driving force, having a role in medical care) and communication around the disease (not focusing on the disease); (b) impact of the disease on the relationship; (c) social impact of the disease on the dyad (social isolation); (d) difficulties and needs of the relative (need to better know the disease). CONCLUSION: This study has highlighted the importance of recognizing the role of the relative in the management of inflammatory arthritis disease, especially when medical decisions are shared with professionals. A joint approach to treatment is a basis for coping with the disease. This approach supposes (a) discussions about relatives' new roles to clarify them, (b) patients' and relatives' communication skills and (c) a good understanding of each other, which can be improved by providing information on the disease and coping strategies for both the patient and the relative.
32075469 Distinct decrease in peripheral lymphocytes in EBER-positive cases of MTX-LPD. 2021 Jan OBJECTIVES: To determine the clinical characteristics of methotrexate-associated lymphoproliferative disorder (MTX-LPD). METHODS: In this study, 12 RA patients who developed MTX-LPD were assessed. The peripheral blood lymphocyte (PBL) count at the onset of MTX-LPD was compared to that 6 months before the onset, in Epstein-Barr virus-encoded RNA (EBER)-positive and -negative subgroups. We examined the change in the PBL count after MTX withdrawal. In patients with relapsed LPD, changes in the PBL count before relapse were also examined. RESULTS: Regression of LPD after MTX withdrawal was noted in eight patients. In these patients, the PBL count was decreased at the onset of MTX-LPD compared to 6 months before the onset; the decrease was significantly more prominent in EBER-positive patients. In cases of spontaneous regression of LPD, the PBL count recovered quickly after MTX withdrawal. Four of eight patients showed a recurrence of LPD after they improved following MTX withdrawal. These patients also exhibited a decreased PBL count at recurrence compared to 6 months before recurrence. CONCLUSION: A decrease in the PBL count might be involved in the pathogenesis of MTX-LPD, especially in EBER-positive cases and in patients with LPD relapse after MTX withdrawal following initial improvement.
32076916 Relative efficacy and safety of iguratimod monotherapy for the treatment of patients with 2020 Jul OBJECTIVES: This study aims to compare the efficacy and the safety of the iguratimod with placebo and other disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis. METHODS: Two authors independently searched and selected randomized controlled trials from Cochrane library, Medline (through Pubmed), and Chinese databases, and then assessed the risk of bias (using ROB 2 tool), and graded the certainty of evidence (using the GRADEpro GDT software). We applied the RevMan 5 software for performing meta-analyses of the final consensus data. RESULTS: We identified 12 trials involving 1938 participants. Ten trials had an overall high risk of bias. Although iguratimod had superior efficacy than placebo, the incidence of adverse events was also higher. Inferring to non-inferiority analysis with other DMARD therapy (primarily comprising methotrexate), iguratimod is likely to result in similar treatment response (20% (OR 1.04, 95% CI 0.79 to 1.36), 50% and 70% improvement in American College of Rheumatology criteria) and functional ability at 24 weeks. Although the disease state was slightly better with iguratimod (MD - 0.55, 95% CI - 0.85 to - 0.25), a clinically important improvement was not achieved. Iguratimod may have lower C-reactive protein and erythrocyte sedimentation rate values. Swollen joint count, tender joint count, pain intensity, and patient's and physician's global assessment of disease state may be comparable between the therapies. Both the therapies are likely to have similar odds (OR 0.91, 95% CI 0.67 to 1.26) of adverse events. CONCLUSION: Our evidence suggests that iguratimod may be considered a potential alternative to methotrexate to treat rheumatoid arthritis.Key Points• The Asia Pacific League of Association for Rheumatology (APLAR) has recommended that iguratimod may be used a first-line drug for rheumatoid arthritis in specific cases.• Patients on iguratimod may have similar treatment response, functional ability, disease state, and adverse event profile at 24 weeks compared with those on methotrexate.• Iguratimod may be considered a better alternative to methotrexate in RA patients having high CRP and ESR values.• Future clinical trials in diverse population comparing the efficacy and safety of iguratimod in monotherapy or combination therapy with DMARDs (other than methotrexate) are warranted.
32715647 Hydroxychloroquine in rheumatic autoimmune disorders and beyond. 2020 Aug 7 Initially used as antimalarial drugs, hydroxychloroquine (HCQ) and, to a lesser extent, chloroquine (CQ) are currently being used to treat several diseases. Due to its cost-effectiveness, safety and efficacy, HCQ is especially used in rheumatic autoimmune disorders (RADs), such as systemic lupus erythematosus, primary Sjögren's syndrome and rheumatoid arthritis. Despite this widespread use in the clinic, HCQ molecular modes of action are still not completely understood. By influencing several cellular pathways through different mechanisms, CQ and HCQ inhibit multiple endolysosomal functions, including autophagy, as well as endosomal Toll-like receptor activation and calcium signalling. These effects alter several aspects of the immune system with the synergistic consequence of reducing pro-inflammatory cytokine production and release, one of the most marked symptoms of RADs. Here, we review the current knowledge on the molecular modes of action of these drugs and the circumstances under which they trigger side effects. This is of particular importance as the therapeutic use of HCQ is expanding beyond the treatment of malaria and RADs.
32281951 Electrocardiogram and heart rate variability assessment in patients with common autoimmune 2020 Apr The aim of this article was to summarize current knowledge about the potential clinical utility of electrocardiogram (ECG) and heart rate variability (HRV) measures in patients with 4 common autoimmune diseases (ADs): rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behcet's disease (BD), and systemic sclerosis (SSc). A search was conducted of the PubMed, Embase, and Scopus databases using terms and a controlled vocabulary associated with these ADs, ECG, and HRV. The available, full-text articles published in English were considered. In all, 20 publications that examined the direct effect of these diseases on the heart were selected according to a systematic review protocol. Time-frequency domain analysis revealed that HRV parameters were lower in patients with the selected ADs in comparison with control groups. An increased QT dispersion and heart rate corrected QT, which are well-known as risk factors for sudden cardiac death, were observed in the patient group. In some studies, a correlation was seen between the duration of the disease and its activity, while others did not report such an association. Heart rate turbulence parameters were also examined. Turbulence onset was increased in SLE and SSc patients, while the turbulence slope was decreased in SLE patients. There was no significant change in these parameters in BD patients. Patients with ADs demonstrate abnormal HRV and ECG parameters, which indicates an autonomic cardiac functional impairment. Measurement of these parameters can be a useful clinical tool in the diagnosis and prediction of some disorders in patients with ADs. Both of these signals can provide helpful information for physicians to trace the efficacy of prescribed medicines.
31025923 Adiponectin promotes fibroblast-like synoviocytes producing IL-6 to enhance T follicular h 2020 Jan OBJECTIVES: Rheumatoid arthritis (RA) is characterised by the overproduction of autoantibodies such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody. T follicular helper (Tfh) cells are a specialised Th subset that provides signals to B cells, promoting the secretion of antibodies. Our previous studies showed that the frequency of circulating Tfh cells were markedly increased in RA patients and positively correlated with disease activity and the levels of anti-CCP autoantibody. Adiponectin (AD) is an adipokine secreted mainly by adipocytes. Our previous work has demonstrated that AD is highly expressed in the inflamed synovial joint tissue and correlates closely with progressive bone erosion in RA patients. However, it remains unknown whether AD aggravates the severity of RA via modulating Tfh cells. This study aims to investigate whether AD exerts effect on Tfh cells in RA. METHODS: CD4+ T cells were purified from peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), and adiponectin receptor 1 (AdipoR1) expression on the surface of CD4+CXCR5+PD-1+ (Tfh) cells was detected by flow cytometry. Purified HC CD4+ T cells were cultured with different concentration fetal bovine serun (FBS) in the presence or absence of AD. The percentages of Tfh cells were analysed by flow cytometry. RA or osteoarthritis (OA) fibroblast-like synoviocytes (FLSs) were stimulated with AD for 72h and then co-cultured with HC CD4+ T cells through cell-to-cell contact or in a transwell system. The percentages of Tfh cells were analysed by flow cytometry and the levels of soluble factors such as interleukin-(IL)-6, IL-21, IL-12 and IFNγ in the supernatants were determined by Human Magnetic Bead Panel or Enzyme linked immunosorbent assay (ELISA). Then anti-IL-6 antibody and/or anti-IL-21 antibody was added to the co-culture system, and the percentages of Tfh cells were analysed by flow cytometry. The frequency of Tfh cells in the joint tissue of collagen-induced arthritis (CIA) mice was examined by flow cytometry. The mRNA expression of Tfh cell transcription factors and functional molecules such as B-cell lymphoma 6 (Bcl-6), B lymphocyte maturation protein 1 (Blimp-1), IL-6, IL-21, IL-12 and IFNγ in the joints of CIA mice were detected by real time PCR (RT-PCR). RESULTS: Adiponectin receptor 1 (AdipoR1) expression was detected on the surface of Tfh cells. However, in the present study, we did not find that AD has a direct effect on Tfh cell generation in vitro. Nonetheless, AD-stimulated RA FLSs could promote Tfh cell generation, predominantly via IL-6 production. And this upregulated effect was partially abolished upon neutralising IL-6. Finally, intraarticular injection of AD aggravated synovial inflammation with increased frequency of Tfh cells in the joints of AD-treated CIA mice. CONCLUSIONS: Our study demonstrated that AD-stimulated RA FLSs promote Tfh cell generation, which is mainly mediated by the secretion of soluble factor IL-6. This finding reveals a novel mechanism for AD in RA pathogenesis.
31474599 Comparative Persistence of Methotrexate and Tumor Necrosis Factor Inhibitors in Rheumatoid 2020 Jun 1 OBJECTIVE: The role of methotrexate (MTX) for the treatment of spondyloarthritis (SpA) remains uncertain. Aims were to compare MTX and tumor necrosis factor inhibitor (TNFi) persistence in spondyloarthritis versus rheumatoid arthritis (RA) and to determine whether concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use is associated with improved TNFi persistence in SpA. METHODS: This retrospective cohort study using Optum's deidentified Clinformatics Data Mart Database 2000-2014 identified patients with RA, psoriatic arthritis (PsA), and ankylosing spondylitis (AS) without prior biologic use who were initiating MTX or a TNFi. Cox proportional hazards models compared time to medication discontinuation over the next 2 years between patients with RA, PsA, or AS, adjusting for potential confounders. In similar analyses stratified by disease, Cox models were used to assess whether concomitant use of csDMARD was associated with TNFi persistence. RESULTS: We identified 31,527 MTX initiators (26,708 RA, 2939 PsA, 1880 AS) and 34,651 TNFi initiators (24,134 RA, 6705 PsA, 3812 AS). MTX was discontinued sooner in patients with PsA [adjusted HR (aHR) 1.10, 95% CI 1.04-1.16] and AS (aHR 1.23, 1.16-1.31) versus RA, while TNFi were discontinued at similar rates in RA and AS and discontinued later in PsA (aHR 0.93, 0.89-0.97). Concomitant use of MTX (compared to no csDMARD) was associated with lower rates of TNFi discontinuation in RA (aHR 0.85, 0.80-0.89), PsA (aHR 0.81, 0.74-0.89), and AS (aHR 0.79, 0.67-0.93). CONCLUSION: MTX discontinuation occurs sooner in patients with PsA and AS versus RA. Concomitant use of MTX with a TNFi, however, is associated with improved TNFi persistence in all 3 diseases.
32831971 Investigating the GWAS-Implicated Loci for Rheumatoid Arthritis in the Pakistani Populatio 2020 Rheumatoid arthritis (RA) is a complex and multifactorial autoimmune disorder with the involvement of multiple genetic and environmental factors. Genome-wide association studies (GWAS) have identified more than 50 RA genetic loci in European populations. Given the anticipated overlap of RA-relevant genes and pathways across different ethnic groups, we sought to replicate 58 GWAS-implicated SNPs reported in Europeans in Pakistani subjects. 1,959 unrelated subjects comprising 1,222 RA cases and 737 controls were collected from three rheumatology facilities in Pakistan. Genotyping was performed using iPLEX or TaqMan® methods. A total of 50 SNPs were included in the final association analysis after excluding those that failed assay design/run or postrun QC analysis. Fourteen SNPs (LINC00824/rs1516971, PADI4/rs2240336, CEP57/rs4409785, CTLA4/rs3087243, STAT4/rs13426947, HLA-B/MICA/rs2596565, C5orf30/rs26232, CCL21/rs951005, GATA3/rs2275806, VPS37C/rs595158, HLA-DRB1/rs660895, EOMES/rs3806624, SPRED2/rs934734, and RUNX1/rs9979383) were replicated in our Pakistani sample at false discovery rate (FDR) of <0.20 with nominal p values ranging from 4.73E-06 to 3.48E-02. Our results indicate that several RA susceptibility loci are shared between Pakistani and European populations, supporting the role of common genes/pathways.
32539813 Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched p 2020 Jun 15 BACKGROUND: This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of 7 biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib (TOF), one of the janus kinase inhibitors, in bDMARDs-naïve and bDMARDs-switched patients with rheumatoid arthritis (RA). METHODS: This study assessed 3897 patients and 4415 treatment courses with bDMARDs and TOF from 2001 to 2019 (2737 bDMARDs-naïve courses and 1678 bDMARDs-switched courses [59.5% of switched courses were their second agent], female 82.3%, baseline age 57.4 years, disease duration 8.5 years; rheumatoid factor positivity 78.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate 4.3; concomitant prednisolone [PSL] dose 6.1 mg/day [usage 42.4%], and methotrexate [MTX] dose 8.5 mg/week [usage 60.9%]). Treatment courses included abatacept (ABT; n = 663), adalimumab (ADA; n = 536), certolizumab pegol (CZP; n = 226), etanercept (ETN; n = 856), golimumab (GLM; n = 458), infliximab (IFX; n = 724), tocilizumab (TCZ; n = 851), and TOF (n = 101/only bDMARDs-switched cases). Drug discontinuation reasons (categorized into lack of effectiveness, toxic adverse events, non-toxic reasons, or remission) and rates were estimated at 36 months using Gray's test and statistically evaluated after adjusted by potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX usage, starting date, and number of switched bDMARDs) using the Fine-Gray model. RESULTS: Cumulative incidence of drug discontinuation for each reason was as follows: lack of effectiveness in the bDMARDs-naïve group (from 13.7% [ABT] to 26.9% [CZP]; P < 0.001 between agents) and the bDMARDs-switched group (from 18.9% [TCZ] to 46.1% [CZP]; P < 0.001 between agents); toxic adverse events in the bDMARDs-naïve group (from 4.6% [ABT] to 11.2% [ETN]; P < 0.001 between agents) and the bDMARDs-switched group (from 5.0% [ETN] to 15.7% [TOF]; P = 0.004 between agents); and remission in the bDMARDs-naïve group (from 2.9% [ETN] to 10.0% [IFX]; P < 0.001 between agents) and the bDMARDs-switched group (from 1.1% [CZP] to 3.3% [GLM]; P = 0.9 between agents). CONCLUSIONS: Remarkable differences were observed in drug retention of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases.
31884118 IDO activation, inflammation and musculoskeletal disease. 2020 Mar The IDO/kynurenine pathway is now established as a major regulator of immune system function. The initial enzyme, indoleamine 2,3-dioxygenase (IDO1) is induced by IFNγ, while tryptophan-2,3-dioxygenase (TDO) is induced by corticosteroids. The pathway is therefore positioned to mediate the effects of systemic inflammation or stress-induced steroids on tissue function and its expression increases with age. Disorders of the musculoskeletal system are a common feature of ageing and many of these conditions are characterized by an inflammatory state. In inflammatory arthritis and related disorders, kynurenine protects against the development of disease, while inhibition or deletion of IDO1 increases its severity. The long-term regulation of autoimmune disorders may be influenced by the epigenetic modulation of kynurenine pathway genes, with recent data suggesting that methylation of IDO may be involved. Osteoporosis is also associated with abnormalities of the kynurenine pathway, reflected in an inversion of the ratio between blood levels of the metabolites anthranilic acid and 3-hydroxy-anthranilic acid. This review discusses evidence to date on the role of the IDO/kynurenine pathway and the highly prevalent age-related disorders of osteoporosis and rheumatoid arthritis and identifies key areas that require further research.
33156359 Temporal artery biopsy for suspected giant cell arteritis: a retrospective analysis. 2021 Oct Temporal artery biopsy (TAB) is one of the diagnostic criteria of giant cell arteritis (GCA) according to 1990 ACR criteria and remains a tool for diagnosis. Although clinicians perform TAB with an intent to confirm suspected GCA, some biopsies result in negative and some lead to non-GCA diagnoses. We aim to review the diagnoses after TAB biopsy performed for suspected GCA and also wanted to evaluate the diagnostic changes and concomitant diseases that develop over time. The patients who had undergone TAB for suspected GCA were identified using the record entry code for TAB. Patients meeting the classification criteria for GCA were designated as the GCA group and not meeting criteria were designated as a non-GCA group. Other classification criteria were implemented for the non-GCA group diseases. A total of 51 patients (Female: 62.7%, median age: 72.1 ± 7.4 years) who had undergone TAB for suspected GCA were evaluated. TAB was positive in 23 (69.6%) of the 33 patients who met the GCA classification criteria. No significant difference was found between TAB-positive and TAB-negative GCA patients in terms of clinical and laboratory parameters. In the non-GCA group, 12 patients had isolated polymyalgia rheumatica (PMR), and the diagnoses of the remaining six patients were as follows: four large vessel vasculitis (LVV) not satisfying GCA diagnostic criteria, one chronic myelomonocytic leukemia (CMML), and one amyloidosis. TAB was negative in all patients with isolated PMR. TAB showed primary amyloidosis in one patient. Out of 33 GCA patients, 21 had "isolated" GCA, four had GCA + Rheumatoid arthritis (RA), seven had GCA + PMR, and one had GCA + polymyositis. RA was diagnosed antecedent to GCA in two patients, and after GCA in the other two patients. One of the patients had developed GCA 20 years after polymyositis had been diagnosed. TAB was found to be positive in two-thirds of patients with suspected GCA. Late-onset RA and rarely other inflammatory rheumatic diseases may develop in the course of GCA.
32240434 Role of HLA-DRB1*04 in the susceptibility and HLA-DRB1*08 in the protection for developmen 2020 Oct Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with an increased prevalence in Mexico. Although its etiology is unknown, its development can be influenced by environmental factors such as smoking and viral infections. But among the factors influencing susceptibility, it is the genetic factors that predominate, mainly the HLA-DRB1 genes, and specifically the alleles that have the shared epitope (SE). A transversal study was performed, in which 31 patients (28 women and 3 men) with RA, treated at the autoimmunity clinic of the High Specialty Hospital Ciudad Salud in Tapachula, Chiapas, southern México, were enrolled. Clinical, biochemical, and demographic data were analyzed; ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), RF (rheumatoid factor), and ACPA (anticitrullinated peptide antibody) were recorded. All patients had at least one positive RA biological marker. For HLA alleles frequencies comparison, we enrolled ethnically matched healthy controls in a ratio of 3:1 for 25 cases and 4:1 for 6 cases in order to guarantee the balance between groups regarding the mean of age and proportion of gender (males vs females). HLA-DRB1*04 was found to be significantly increased in patients compared with ethnically matched healthy controls (p 0.0007, OR: 2.8, 95% CI 1.5-5.1); contrarily, DRB1*08 showed a protective effect (p 0.005, OR 0.1). This paper confirmed the involvement of HLA genes on risk determination for RA in a population of Mexican Mestizos from Tapachula, Chiapas. Key Points • HLA-DRB1*04 confirms the increased risk of rheumatoid arthritis. • HLA-DRB1*08 showed a more definite protective effect in southern Mexicans mestizos, a population with more Amerindian ancestry.
32430630 A useful tool to assess quality of LIFE in rheumatoid arthritis patients that does not req 2020 Nov To validate the Quality of Life-Rheumatoid Arthritis Scale II (QOL-RA II) in an Argentinean cohort of patients with rheumatoid arthritis (RA). Patients ≥ 18 years old, with a diagnosis of RA according to ACR-EULAR 2010 criteria, were included in a cross-sectional study. Sociodemographic data, comorbidities, RA characteristics, disease activity, and current treatment were registered. Questionnaires were administered, including EQ-5D-3 L, QOL-RA II, HAQ-A, and PHQ-9. The QOL-RA II was re-administered in 20 patients to evaluate reproducibility. Four hundred and thirty patients were included. Median QOL-RA was 6.6 (IQR 5.3-8). Mean time to complete it was 1.7 ± 0.57 min and to calculate it was 12 ± 1.7 s. It showed very good reliability (Cronbach's alpha 0.97), reproducibility (ICC, 0.96), and good correlation between the different items and the total questionnaire, without evidence of redundancy. Besides, QOL-RA II presented good correlation with EQ-5D-3L (Rho, 0.6) and moderate with DAS28 (Rho, 0.38), and CDAI (Rho, 0.46). Worse quality of life was observed in patients not doing physical activity, unemployed, and current smokers. Patients with higher disease activity had a significant poorer quality of life. Adjusting by age, sex and disease duration, unemployment, higher disease activity, disability, and the presence of depression were independently associated to worse quality of life. QOL-RA II demonstrated good construct validity, reproducibility, and reliability. It was easy to complete and calculate and does not require a license for its use, thus making it the optimal tool for assessing the quality of life in Spanish-speaking patients with RA. Key Points • The evaluation of quality of life is very important in patients with Rheumatoid Arthritis. • Most of the questionnaires used to assess the quality of life require a license to use. • QOL-RA II is a valid and simple questionnaire to evaluate the quality of life of patients with RA and does not require a license for its use.
30583870 Association between Overweight/Obesity and Clinical Activity in Rheumatoid Arthritis. 2020 Nov INTRODUCTION: The effect of overweight/obesity on clinical status in rheumatoid arthritis (RA) is still a controversial topic. AIM: To assess the association between body composition and clinical status in RA patients. METHODS: A prospective, comparative, cross-sectional study was performed on 123 (98.4% women, 86.3% FR+, 9.3±8.7 duration years) RA patients diagnosed according to ACR/EULAR 2010 criteria who were assessed for inflammatory activity (DAS 28), functional status (HAQ-Di), and type of treatment. Body composition was evaluated by BMI, waist, hip, and middle arm girths, waist/hip ratio, skin fold measurements, and bioelectrical impedance analysis. RESULTS: The prevalence of overweight and obesity (BMI-WHO cut-off points) was 30.9% and 45.5% respectively. Using Stavropoulos-Kalinoglou cut-off points, each corresponding prevalence increased to 31.7% and 58.5%, respectively. Pooled patients in the overweight/obesity classification (Stavropoulos-Kalinoglou classification) exhibited a significantly higher number of swollen joints as compared to subnormal/normal body composition subjects (3.8±3.3 vs. 1.9±2.5; p=.02). Swollen joint count showed significant positive correlation with 6 out of 11 body composition parameters: BMI; arm and hip girths, triceps skin fold, body fat average determined by bioelectrical impedance analysis, and skin fold measurements. CONCLUSIONS: Prevalence of obesity in RA varies according to BMI cut-off points. Overweight and obesity were associated with higher inflammatory activity characterized by a higher count of tender and swollen joints. A positive correlation was found between swollen joint amount and the majority of the body fat mass indicators assessed. Body composition assessment/improvement should be an important part of the routine care of RA patients.
32275944 Regulatory T cells in patients with early untreated rheumatoid arthritis: Phenotypic chang 2020 Jul Rheumatoid arthritis (RA) is frequent systemic autoimmune disease characterized by excessive activation of collagen-specific T helper cells, and elevated level of autoantibodies in the serum. Development of RA is associated with defect in compartment of regulatory CD4+Foxp3+ T cells (Treg), but data concerning suppressive potential of Treg population in RA patients are contradictory and depend on the stage of disease. In this study we aimed to characterize abundance and phenotypic markers of CD4+Foxp3+ Treg in peripheral blood of healthy donors compared to untreated early RA patients to find potential correlations with the disease activity, antibody level, and absolute numbers and proportion of different subpopulations of T cells. Moreover, we assessed the influence of methotrexate (MT) treatment on percentage and absolute numbers of CD4+Foxp3+ Treg from the peripheral blood of untreated early RA patients. We demonstrate that increase and phenotypic changes in Treg population correlate well with response to MT. Analysis of the cohorts of matched RA patients (n = 45) and healthy controls (n = 20) revealed that patients with untreated early RA demonstrate substantial decrease in blood Treg percentage and absolute number, as well as low level of activated Treg surface markers in comparison to healthy control. The defect in Treg compartment negatively correlates with both RA activity and antibody level. MT treatment of patients with early untreated RA increases both proportion and absolute number of Treg with high level of activation markers, suggesting an increase of their functional capacity. Here we speculate the role of Tregs as specific cellular marker of successful RA treatment.
31390271 Discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis 2020 May Objectives: To evaluate the efficacy and safety of methotrexate (MTX) discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing combination therapy with tocilizumab (TCZ) plus MTX.Methods: This multicenter, open-label, uncontrolled, prospective study included RA patients maintaining low disease activity (Clinical Disease Activity Index (CDAI) ≤10) for ≥12 weeks with TCZ plus MTX. Methotrexate was discontinued following 12 weeks of biweekly administration while continuing TCZ therapy. The primary endpoint was the proportion of patients maintaining low disease activity with no flare at week 36.Results: A total of 49 patients completed 36 weeks of therapy. The proportion of patients maintaining low disease activity at week 36 was 75.5%. The lower limit of the 95% confidence interval exceeded the assumed threshold response rate of 60%, demonstrating the clinical feasibility of MTX discontinuation. The prevalence of gastroesophageal reflux disease, defined as a Frequency Scale for Symptoms of Gastroesophageal reflux disease score ≥8, significantly decreased from week 0 to 12 (27.1-18.4%; p= .025).Conclusion: Discontinuation of concomitant MTX is clinically feasible for maintaining low disease activity, and may be beneficial from the perspective of reducing gastrointestinal symptoms in Japanese RA patients treated with TCZ. Trial registration number: UMIN000021247.
31522318 Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rhe 2020 Jan OBJECTIVES: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS. PATIENTS AND METHODS: Thirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (βCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months. RESULTS: TNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/βCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and βCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline βCTX, while femoral neck BMD rather showed inverse correlations with CRP. CONCLUSIONS: Anti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and βCTX in RA, whilst CRP in AS.Key Points• One-year anti-TNF therapy halted generalized bone loss in association with clinical improvement in arthritides.• Anti-TNF therapy may inversely act on DKK-1 and SOST.• Independent predictors of BMD were SOST and βCTX in RA, while CRP in AS.
32128609 Chemosensory function is decreased in rheumatoid arthritis. 2020 Jun PURPOSE: Research indicates that rheumatic disorders are accompanied by decreased chemosensory function. The present study aimed to specifically evaluate this issue in patients with rheumatoid arthritis (RA). METHODS: 212 RA patients (43 men, 169 women, mean age 59 ± 13.3 years), and 30 healthy controls (10 men, 20 women, mean age 40 ± 15.3 years), were included in this study. Chemosensory measurements consisted of olfactory testing using the "Sniffin' Sticks" test battery (with odor thresholds, odor discrimination and odor identification; OT, OD, OI) and gustatory testing on a suprathreshold and a quasi-threshold level using "taste sprays" and "taste strips", respectively. In addition, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) and RA autoantibodies (anti-cyclic citrullinated peptides, RA factors) were evaluated. RESULTS: Olfactory measurements showed 4% of the RA patients functionally anosmic and 40% hyposmic. RA patients scored significantly lower in suprathreshold olfactory tests (OD, OI) compared to controls (OI: 12.5 ± 2.5 vs. 14.1 ± 1.3; OD: 11.3 ± 2.7 vs. 12.9 ± 1.7). In addition, RA patient had decreased taste function compared to healthy individuals (10.4 ± 2.6 vs. 11.7 ± 1.7). Chemosensory function did not correlate with parameters related to the severity of disease. CONCLUSION: Chemosensory function (taste, OD and OI) appears to be decreased in RA patients. In contrast, OT was not affected. Changes in chemosensory function seem to be independent of disease parameters such as duration of disease or disease activity.