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ID PMID Title PublicationDate abstract
32991416 Efficacy and safety of total glucosides of paeony for rheumatoid arthritis: A protocol for 2020 Sep 25 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by erosion of joints and surrounding tissues. RA not only causes the decline of patients' physical function and quality of life, but also brings huge economic burden to patients' families and society. Total glucosides of paeony (TGP) is commonly used in treating RA in China. At present, there are many clinical reports about this medicine, but these reports have their own flaws. Therefore, there is an urgent need for systematic review and meta-analysis of the existing clinical evidence. METHODS AND ANALYSIS: Literature search will be carried out in 6 databases, and the literatures will be screened according to the inclusion and exclusion criteria. The clinical effective rate will be taken as primary outcome. Serum rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, Western Ontario and McMaster before and after treatment and adverse effects will be secondary outcomes. The heterogeneity of the study will be examined by χ and I test. To identify the source of heterogeneity, subgroup analysis will be carried out. The sensitivity test will be conducted investigate the stability of results. Funnel plot and Egger test will be used to evaluate publication bias. Finally, the quality of evidence will be summarized. RESULTS: The results will be published in peer-reviewed journals. CONCLUSIONS: This study will systematically evaluate the efficacy of TGP in the treatment of RA. The results of this study can better guide clinical practice. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/85QVF.
32661554 [Perioperative management in the treatment of trauma for rheumatics under immunosuppressio 2020 Aug With an almost 3.5% manifestation rate in Germany, rheumatoid arthritis is a relatively frequent disease. Due to the involvement of diverse locations on the skeleton and often multiple comorbidities, treatment of these patients in cases of acute trauma potentially represents a substantial risk. The anti-inflammatory drug treatment harbors dangers, such as delayed wound healing and infections in the perioperative management of these patients. In an emergency a modification of the basic anti-inflammatory medication is hardly possible, so that the postoperative phase after trauma surgery is of special importance. If necessary, orthopedic or internist rheumatologists should be consulted for additional support. Absolute and urgent surgical interventions do not constitute a contraindication with respect to the antirheumatic medication but should be considered in the assessment of the perioperative risk profile. A close cooperation with anesthesia, the meticulous control of intraoperative positioning and postoperative management are of particular importance.
33046136 The Janus kinase 1/2 inhibitor baricitinib reduces biomarkers of joint destruction in mode 2020 Oct 12 BACKGROUND: Tissue released blood-based biomarkers can provide insight into drug mode of action and response. To understand the changes in extracellular matrix turnover, we analyzed biomarkers associated with joint tissue turnover from a phase 3, randomized, placebo-controlled study of baricitinib in patients with active rheumatoid arthritis (RA). METHODS: Serum biomarkers associated with synovial inflammation (C1M, C3M, and C4M), cartilage degradation (C2M), bone resorption (CTX-I), and bone formation (osteocalcin) were analyzed at baseline, and weeks 4 and 12, from a subgroup of patients (n = 240) randomized to placebo or 2-mg or 4-mg baricitinib (RA-BUILD, NCT01721057). Mixed-model repeated measure was used to identify biomarkers altered by baricitinib. The relationship between changes in biomarkers and clinical measures was evaluated using correlation analysis. RESULTS: Treatment arms were well balanced for baseline biomarkers, demographics, and disease activity. At week 4, baricitinib 4-mg significantly reduced C1M from baseline by 21% compared to placebo (p < 0.01); suppression was sustained at week 12 (27%, p < 0.001). Baricitinib 4-mg reduced C3M and C4M at week 4 by 14% and 12% compared to placebo, respectively (p < 0.001); they remained reduced by 16% and 11% at week 12 (p < 0.001). In a pooled analysis including all treatment arms, patients with the largest reduction (upper 25% quartile) in C1M, C3M, and C4M by week 12 had significantly greater clinical improvement in the Simplified Disease Activity Index at week 12 compared to patients with the smallest reduction (lowest 25% quartile). CONCLUSION: Baricitinib treatment resulted in reduced circulating biomarkers associated with joint tissue destruction as well as concomitant RA clinical improvement. TRIAL REGISTRATION: ClinicalTrials.gov NCT01721057 ; date of registration: November 1, 2012.
32235044 Immobilization of novel inorganic nano-complexes onto MWCNT nanomaterials as a novel adsor 2020 Jul 24 Novel supported inorganic metal nano-complexes of Ag(I) and Co(II) derived from 4-amino-N-(4-methylpyrimidin-2-yl) benzene sulfonamide (SulMer) were synthesized using olive leaf extract as a reducing agent with grinding and microwave methods. The prepared samples were denoted as Comp1-6. The surface morphologies of the synthesized nanomaterials were analyzed using C, H, N, S analysis, Fourier-transform infrared spectroscopy, UV- visible spectroscopy, proton and carbon nuclear magnetic resonance, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, and x-ray powder diffraction (XRD) analysis. The data revealed that all the synthesized complexes exhibited a 1:1 metal-to-ligand ratio with a coordination number of 4 or 6. The mean particle size of the nanomaterial samples was 25-35 nm. The XRD patterns indicated a crystalline nature for the complexes. The supported inorganic metal nano-complexes displayed good activity in the adsorptive removal of Direct Red 81 (DR-81) from aqueous solutions. In addition, the effect of the supported metal nano-complexes on the immune system was studied as well as how these anti-inflammatory compounds could be used to treat many autoimmune diseases, most notably rheumatoid arthritis. An experimental model for arthritis can be induced using complete Freund's adjuvant. It was shown that the supported complex offers several advantages such stability, eco-friendliness, simple experimental conditions, short reaction times, and easy work- up.
31112011 Treatment Strategies in Early Rheumatoid Arthritis Methotrexate Management: Results From a 2020 Aug OBJECTIVE: To assess real-world practice patterns surrounding treatment initiation and adjustments over time for methotrexate (MTX) and non-MTX-based treatment strategies in early rheumatoid arthritis (RA). METHODS: We studied a multicenter, incident early RA cohort (enrolled 2007-2017 within 1 year of symptoms) who fulfilled American College of Rheumatology/European League Against Rheumatism criteria. Adult patients with RA were eligible if treatment with MTX (± other disease-modifying antirheumatic drugs [DMARDs]) was initiated within 90 days of cohort entry. We compared time until treatment change for 4 initial MTX-based therapies and time to second treatment change after the first change. The definition of treatment change included changing of route for MTX monotherapy, adding or stopping a DMARD or biologic, and changing dose/frequency of a DMARD or biologic. RESULTS: There was great variability of treatment at initiation and during therapy adjustment. In 1,484 patients with early RA, the majority initiated MTX monotherapy (oral or subcutaneous [SC]). Patients receiving SC MTX monotherapy changed treatment less (45% versus 79%) and remained on treatment longer (hazard ratio [HR] 0.52 [95% confidence interval (95% CI) 0.4-0.67]) than those receiving oral MTX monotherapy. Most therapy adjustments involved adding a DMARD or changing to a non-MTX DMARD. Those adults taking biologics and who were receiving triple therapy had a longer time without treatment change (HR 0.26 [95% CI 0.16-0.42] and HR 0.57 [95% CI 0.38-0.85], respectively). CONCLUSION: We found large variability in the way MTX-based therapies are prescribed in clinical practice. Our findings support the use of SC MTX monotherapy or MTX combination as initial therapy. For subsequent treatment after initial MTX-based therapy, those patients initiating either biologics or triple therapy had a longer time to treatment change than oral MTX monotherapy.
32005430 Connective Tissue Disease Related Interstitial Lung Disease. 2020 Mar Patients with connective tissue diseases may have pulmonary involvement, including interstitial lung disease. Various patterns of interstitial lung disease have been classically described in certain connective tissue diseases. It is now recognized that there is significant overlap between patterns of interstitial lung disease observed in the various connective tissue diseases. Differentiating idiopathic from connective tissue disease-related interstitial lung disease is challenging but of clinical importance. New concepts in the diagnosis of connective tissue disease related interstitial lung disease may prove useful in making the diagnosis.
32621138 French survey on the crossed needs on sexual health for chronic inflammatory rheumatism pa 2020 Sep Patients with Inflammatory Chronic Rheumatic disease have approximately three times more sexual dysfunction than the healthy population. However, health professionals do not dare to discuss the subject with them, largely because they do not feel educated on the subject. To define the educational needs in the sexual health of health professionals involved in patient education and those of patients with Inflammatory Chronic Rheumatic disease. This French multicenter cross-sectional online study included health professionals involved in patient education and patients with Inflammatory Chronic Rheumatic disease. Two surveys were designed to assess, both of them the specific needs. They were filled out anonymously online with a secured server. The influence of professionals and patients' characteristics on their sexual health needs were tested. 57 health professionals and 239 patients answered. 71,6% of the patients reported sexual difficulties and 79,9% had never discussed them with health professionals. To facilitate discussion, the health professionals most often wanted a colleague specialized in sexual health in their team (59,7%) and access to tools (52,6%). The patients' primary expectations were psychological support (65.7%), information (51.9%), and referral to specialists if needed (43.1%). The topics the health professionals and patients considered most useful were adverse effects of treatment and impact of rheumatism on sexuality and body image. 70,2% of the health professionals felt they needed training. This survey demonstrates the need to offer educational training to health professionals designed to enable them to address and discuss sexual health issues and give their patients appropriate advice.
32990114 Simplified disease activity index and clinical disease activity index before and during pr 2021 Jul OBJECTIVES: We explored rheumatoid arthritis (RA) disease activity before, during, and after pregnancy in patients treated with tight control and investigated the association between disease activity in the postpartum period and those before and during pregnancy. METHODS: We retrospectively reviewed disease activity and medications of 27 patients before pregnancy, at every trimester, and in the postpartum period. RESULTS: Prednisolone was administered to 33% of patients with a median dose of 0 (0-2.5) mg/day and biologic agents was 78% in the third trimester. The median remission rates during all periods were the Disease Activity Score-28-C-reactive Protein assessed with three variables (DAS28-CRP-3) 85%, Simplified Disease Activity Index (SDAI) 55%, and Clinical Disease Activity Index (CDAI) 54%. Although SDAI and CDAI decreased significantly from before pregnancy to the first trimester and increased from the third trimester to the postpartum period, DAS28-CRP-3 did not change during all periods. Although SDAI and CDAI before and during pregnancy were significantly correlated with those in the postpartum period, DAS28-CRP-3 was not. CONCLUSIONS: Tight control before pregnancy suppressed RA disease activity during pregnancy and in the postpartum period. SDAI/CDAI before and during pregnancy were predictive for disease activity in the postpartum period.
32678001 Presence of autoantibodies in "seronegative" rheumatoid arthritis associates with classica 2020 Jul 16 BACKGROUND: Rheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibodies in the RA subset that is traditionally defined as seronegative. METHODS: Anti-CCP2 IgG, 19 ACPA fine-specificities, IgM/IgG/IgA RF, anti-carbamylated-protein (CarP) antibodies, and 17 other autoantibodies, were analysed in 2755 RA patients and 370 controls. Antibody prevalence, levels, and co-occurrence were examined, and associations with risk factors and disease activity during 5 years were investigated for different antibody-defined RA subsets. RESULTS: Autoantibodies were detected in a substantial proportion of the traditionally defined seronegative RA subset, with ACPA fine-specificities found in 30%, IgA/IgG RF in 9.4%, and anti-CarP antibodies in 16%, with a 9.6% co-occurrence of at least two types of RA-associated autoantibodies. HLA-DRB1 shared epitope (SE) associated with the presence of ACPA in anti-CCP2-negative RA; in anti-CCP2-positive RA, the SE association was defined by six ACPA fine-specificities with high co-occurrence. Smoking associated with RF, but not with ACPA, in anti-CCP2-negative RA. Presence of ACPA and RF, but not anti-CarP antibodies, in conventionally defined "seronegative" RA, associated with worse clinical outcome. CONCLUSIONS: "Seronegative" RA is not truly a seronegative disease subset. Additional screening for ACPA fine-specificities and IgA/IgG RF defines a group of patients that resembles seropositive patients with respect to risk factors and clinical picture and may contribute to earlier diagnosis for a subset of anti-CCP2-/IgM RF- patients with a high need for active treatment.
33151161 Asynchronous mHealth Interventions in Rheumatoid Arthritis: Systematic Scoping Review. 2020 Nov 5 BACKGROUND: Mobile devices such as smartphones and tablets have surged in popularity in recent years, generating numerous possibilities for their use in health care as mobile health (mHealth) tools. One advantage of mHealth is that it can be provided asynchronously, signifying that health care providers and patients are not communicating in real time. The integration of asynchronous mHealth into daily clinical practice might therefore help to make health care more efficient for patients with rheumatoid arthritis (RA). The benefits have been reviewed in various medical conditions, such as diabetes and asthma, with promising results. However, to date, it is unclear what evidence exists for the use of asynchronous mHealth in the field of RA. OBJECTIVE: The objective of this study was to map the different asynchronous mHealth interventions tested in clinical trials in patients with RA and to summarize the effects of the interventions. METHODS: A systematic search of Pubmed, Scopus, Cochrane, and PsycINFO was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies were initially screened and later assessed by two independent researchers. Disagreements on inclusion or exclusion of studies were resolved by discussion. RESULTS: The literature search yielded 1752 abstracts. After deduplication and screening, 10 controlled intervention studies were included. All studies were assessed to be at risk for bias in at least one domain of the Cochrane risk-of-bias tool. In the 10 selected studies, 4 different types of mHealth interventions were used: SMS reminders (to increase medication adherence or physical activity; n=3), web apps (for disease monitoring and/or to provide medical information; n=5), smartphone apps (for disease monitoring; n=1), and pedometers (to increase and track steps; n=1). Measured outcomes varied widely between studies; improvements were seen in terms of medication compliance (SMS reminders), reaching rapid remission (web app), various domains of physical activity (pedometer, SMS reminders, and web apps), patient-physician interaction (web apps), and self-efficacy (smartphone app). CONCLUSIONS: SMS reminders, web apps, smartphone apps, and pedometers have been evaluated in intervention studies in patients with RA. These interventions have been used to monitor patients or to support them in their health behavior. The use of asynchronous mHealth led to desirable outcomes in nearly all studies. However, since all studies were at risk of bias and methods used were very heterogeneous, high-quality research is warranted to corroborate these promising results.
32157196 Pharmacomicrobiomics in inflammatory arthritis: gut microbiome as modulator of therapeutic 2020 May In the past three decades, extraordinary advances have been made in the understanding of the pathogenesis of, and treatment options for, inflammatory arthritides, including rheumatoid arthritis and spondyloarthritis. The use of methotrexate and subsequently biologic therapies (such as TNF inhibitors, among others) and oral small molecules have substantially improved clinical outcomes for many patients with inflammatory arthritis; for others, however, these agents do not substantially improve their symptoms. The emerging field of pharmacomicrobiomics, which investigates the effect of variations within the human gut microbiome on drugs, has already provided important insights into these therapeutics. Pharmacomicrobiomic studies have demonstrated that human gut microorganisms and their enzymatic products can affect the bioavailability, clinical efficacy and toxicity of a wide array of drugs through direct and indirect mechanisms. This discipline promises to facilitate the advent of microbiome-based precision medicine approaches in inflammatory arthritis, including strategies for predicting response to treatment and for modulating the microbiome to improve response to therapy or reduce drug toxicity.
31676691 Whole Blood Targeted Bisulfite Sequencing and Differential Methylation in the C6ORF10 Gene 2020 Nov 1 OBJECTIVE: Polymorphisms in human major histocompatibility complex (MHC) are the strongest genetic associations with rheumatoid arthritis (RA). Epigenome-wide methylation studies suggest DNA methylation changes within MHC may contribute to disease susceptibility. We profiled MHC-specific methylated CpG (5'-C-phosphate-G-3') in autoantibody-positive patients with RA and matched unaffected anticitrullinated protein antibodies-negative first-degree relatives (ACPA-/FDR) from an indigenous North American (INA) population that is known to have prevalent RA. METHODS: DNA was isolated from whole blood and targeted bisulfite sequencing was used to profile methylated CpG in patients with RA and ACPA-/FDR. Differentially methylated CpG loci (DML) were mapped and gene annotated. Ingenuity pathway analysis (IPA) was used for curating biomolecular networks of mapped genes. Transcript abundance was determined by quantitative (q)PCR. RESULTS: We identified 74 uniquely methylated CpG sites within the MHC region that were differentially methylated in patients with RA (p < 0.05), compared to ACPA-/FDR. Of these, 32 DML were located on 22 genes. IPA showed these genes are involved in regulating the nuclear factor-κB complex and processes involved in antigen presentation, and immune cell crosstalk in autoimmunity. Pearson correlation analysis demonstrated a negative association between differentially methylated CpG in the C6ORF10 gene and risk factors associated with RA. Analysis by qPCR confirmed differential abundance of C6ORF10, TNXB, and HCG18 mRNA in patients with RA compared to ACPA-/FDR. CONCLUSION: Our results confirm the presence of differential methylation at specific gene loci within the MHC region of INA patients with RA. These epigenetic signatures may precede disease onset, or alternatively, may be a result of developing RA.
32004586 TRAIL-expressing cell membrane nanovesicles as an anti-inflammatory platform for rheumatoi 2020 Apr 10 Rheumatoid arthritis (RA) is one of the most common chronic autoimmune diseases. Although the progress made with current clinical use of biologic disease-modifying antirheumatic drugs (bioDMARDs), the response rate of RA treatment remains ungratified, primarily due to intricacy interactions of multiple inflammatory cytokines and the awkward drug delivery. Thus, it is of great importance to neutralize cytokines and actively deliver therapeutic agents to RA joints for the purpose of promoting in situ activity. Herein, we proposed and validated a nanoparticle-based broad-spectrum anti-inflammatory strategy for RA management by fusing TRAIL-anchored cell membranes onto drug-loaded polymeric cores (TU-NPs), which makes them ideal decoys of inflamed macrophage-targeted biological molecules. Upon intravenous injection of TU-NPs into collagen-induced arthritic mice, the fluorescence/photoacoustic dual-modal imaging revealed higher accumulations and longer retention of TU-NPs in inflamed joints. In vivo therapeutic evaluations suggested that these nanoparticles could neutralize cytokines, suppress synovial inflammation, and provide strong chondroprotection against joint damage by targeting and deep penetration into the inflamed tissues. Overall, our work provides a novel strategy to treat RA with a strong potential for clinical translation.
31498068 Increased serum levels of microfibrillar-associated protein 4 (MFAP4) are not associated w 2020 Jan OBJECTIVES: To study circulating MFAP4 in rheumatoid arthritis (RA) and its associations with clinical phenotype. METHODS: Early RA (ERA): 47 patients with newly diagnosed, treatment naïve RA were included. Serum MFAP4, clinical and laboratory disease variables were recorded serially during 12 months of intensive synovitis suppressive treatment. Long-standing RA (LRA): 317 patients participated, all receiving DMARD treatment. Disease activity, autoantibody status, extra-articular manifestations and cardiovascular morbidity were recorded. Paired serum and synovial fluid samples were obtained from 13 untreated ERA patients. Healthy blood donors served as reference points. MFAP4 was quantified by AlphaLISA immunoassay. Univariate, multivariate and mixed effects regression models were applied in the statistical analysis. RESULTS: ERA: MFAP4 increased from baseline and was significantly elevated at the 12-month follow-up, 17.8 U/l [12.6;24.1] vs. healthy controls, 12.7 U/l [9.5;15.6], p<0.001. MFAP4 did not correlate with joint counts or C-reactive protein. LRA: MFAP4 was increased, 25.9 U/l [20.4;33.7] vs. healthy controls, 17.6 U/l [13.7;21.2], p<0.0001, but did not correlate with disease activity measures or presence of extra-articular manifestations. Notably, MFAP4 correlated inversely with smoking (p<0.0001) and presence of antibodies against cyclic citrullinated peptides (anti-CCP), p=0.005. There was a positive association with systolic blood pressure, p=0.001 and co-occurrence of three cardiovascular events and/or risk factors, p<0.0001. The serum:synovial fluid MFAP4 ratio was 2:1. CONCLUSIONS: MFAP4 increases from diagnostic baseline despite intensive treatment but does not associate with synovitis at early or late stages of RA. Correlation patterns indicate that increased MFAP4 may reflect enhanced RA-related vascular remodelling.
33017281 Potential of B-cell-targeting therapy in overcoming multidrug resistance and tissue invasi 2021 Sep Rheumatoid arthritis (RA) is a systemic autoimmune mediated inflammatory disease characterized by progressive joint damage and extra-articular organ manifestations. Among the effector pathways and cells involved in the development of RA, activated B cells play a pivotal role in the pathological process of RA. P-glycoprotein (P-gp), a member of ATP-binding cassette transporters, is induced on the cell membrane by certain stimuli. P-gp transports various drugs from the cytoplasm to the cell exterior, resulting in the development of drug resistance. P-gp expression on B cells appears in patients with RA as the disease activity increases, and treatment of these patients' results in modification of over-expression of P-gp on activated B cells. Evidence suggests that P-gp expressing-activated B cells play important roles in the pathogenesis and treatment resistance in RA through the efflux of intracellular drugs and progression of infiltration in inflammatory lesions. Therapies designed to target activated B cells might overcome refractory RA. Identification of the subsets of peripheral activated B cells that express P-gp in RA patients might help the selection of suitable treatment strategy.
32372140 Anxiety and depression in reproductive age women with rheumatic diseases. 2020 Sep Women in reproductive age with rheumatic diseases (RD) are especially vulnerable for depression and anxiety which negatively impacts the pregnancy, birth, and RD. The purpose of this study is to describe the frequency of anxiety and depression symptoms employing the Hospital Anxiety and Depression Scale (HADS) in women in reproductive age. We conducted an observational, single-center, cross-sectional, and descriptive study in reproductive-age, non-pregnant women without a prior psychiatric diagnosis. Differences between disease groups, subscale results, and disease activity were analyzed with the Chi square, Mann-Whitney U test, or Kruskal-Wallis test. A total of 100 women were included. Mean age was 35.3 years (SD = 10.07). The most frequent diagnosis was rheumatoid arthritis (RA) with 48, followed by systemic lupus erythematosus (SLE) with 30. A total of 66 (66%) patients had an abnormal HADS score (probable or possible cases) in either subscale. More than 50% of RA patients had an abnormal HADS score. We found an association between RA disease activity groups and total HADS score (p = 0.003). Furthermore, we found a statically significant association between RA activity groups and HADS anxiety subscales group classification (p = 0.01). No differences between disease activity groups of SLE or other diseases and HADS classification or total score was found (p = 0.277). A high frequency of probable or possible cases of depression and anxiety were recognized in reproductive-age women with RD. A high RA disease activity was associated with a high total HADS score and an increased presence of anxiety symptoms.
33087107 Identifying frailty in trials: an analysis of individual participant data from trials of n 2020 Oct 22 BACKGROUND: Frailty is common in clinical practice, but trials rarely report on participant frailty. Consequently, clinicians and guideline-developers assume frailty is largely absent from trials and have questioned the relevance of trial findings to frail people. Therefore, we examined frailty in phase 3/4 industry-sponsored clinical trials of pharmacological interventions for three exemplar conditions: type 2 diabetes mellitus (T2DM), rheumatoid arthritis (RA), and chronic obstructive pulmonary disease (COPD). METHODS: We constructed a 40-item frailty index (FI) in 19 clinical trials (7 T2DM, 8 RA, 4 COPD, mean age 42-65 years) using individual-level participant data. Participants with a FI > 0.24 were considered 'frail'. Baseline disease severity was assessed using HbA1c for T2DM, Disease Activity Score-28 (DAS28) for RA, and % predicted FEV1 for COPD. Using generalised gamma regression, we modelled FI on age, sex, and disease severity. In negative binomial regression, we modelled serious adverse event rates on FI and combined results for each index condition in a random-effects meta-analysis. RESULTS: All trials included frail participants: prevalence 7-21% in T2DM trials, 33-73% in RA trials, and 15-22% in COPD trials. The 99th centile of the FI ranged between 0.35 and 0.45. Female sex was associated with higher FI in all trials. Increased disease severity was associated with higher FI in RA and COPD, but not T2DM. Frailty was associated with age in T2DM and RA trials, but not in COPD. Across all trials, and after adjusting for age, sex, and disease severity, higher FI predicted increased risk of serious adverse events; the pooled incidence rate ratios (per 0.1-point increase in FI scale) were 1.46 (95% CI 1.21-1.75), 1.45 (1.13-1.87), and 1.99 (1.43-2.76) for T2DM, RA, and COPD, respectively. CONCLUSION: The upper limit of frailty in trials is lower than has been described in the general population. However, mild to moderate frailty was common, suggesting trial data may be harnessed to inform disease management in people living with frailty. Participants with higher FI experienced more serious adverse events, suggesting screening for frailty in trial participants would enable identification of those that merit closer monitoring. Frailty is identifiable and prevalent among middle-aged and older participants in phase 3/4 drug trials and has clinically important safety implications.
31897954 The evaluation of gene polymorphisms associated with autoinflammatory syndrome in patients 2020 Mar OBJECTIVES: Palindromic rheumatism (PR) is a type of acute arthritis or periarthritis characterized by recurrence, paroxysmal, or intermittent disease attacks and occasionally progresses to other types of rheumatic disease. PR patients who are anti-citrullinated protein antibodies (ACPA)-negative have a high prevalence of MEFV gene polymorphisms, and intermittent hydrarthrosis (IH) is also associated with MEFV polymorphisms. The purpose of this study was to evaluate the clinical characteristics of and autoinflammatory syndrome-associated gene polymorphisms in patients with PR and IH and to identify predictive factors for developing other rheumatic diseases. METHODS: Six PR patients (four females; median age at disease onset, 20.0 years; median age at evaluation, 47.0 years) were retrospectively evaluated for clinical features and polymorphisms in genes responsible for autoinflammatory diseases. RESULTS: All six patients fulfilled the diagnostic criteria for PR and showed clinical feature of IH. Two presented with recurrent fever. All six patients were negative for rheumatoid factor and ACPA and had normal articular X-ray findings. Among the six patients, MEFV gene polymorphisms known to cause FMF were identified in four, CIAS1 mutation was observed in one, and TNFRSFIA mutation was observed in one. Colchicine was effective in three patients with MEFV polymorphisms. The other five patients continued to experience PR, although three patients achieved remission with medication. CONCLUSIONS: PR presenting with IH might be associated with gene polymorphisms responsible for autoinflammatory diseases; colchicine appears to be effective in these patients.Key Point• Palindromic rheumatism with intermittent hydrarthrosis might be associated with gene polymorphisms responsible for autoinflammatory diseases.
31859346 Effectiveness and safety over 3 years after the 2-year U-Act-Early trial of the strategies 2020 Sep 1 OBJECTIVES: U-Act-Early was a 2-year, randomized placebo controlled, double-blind trial, in which DMARD-naïve early RA patients were treated to the target of sustained remission (SR). Two strategies initiating tocilizumab (TCZ), with and without methotrexate (MTX), were more effective than a strategy initiating MTX. The aim of the current study was to determine longer-term effectiveness in daily clinical practice. METHODS: At the end of U-Act-Early, patients were included in a 3-year post-trial follow-up (PTFU), in which treatment was according to standard care and data were collected every 3 months during the first year and every 6 months thereafter. Primary end point was disease activity score assessing 28 joints (DAS28) over time. Mixed effects models were used to compare effectiveness between initial strategy groups, correcting for relevant confounders. Between the groups as randomized, proportions of patients were tested for DMARD use, SR and radiographic progression of joint damage. RESULTS: Of patients starting U-Act-Early, 226/317 (71%) participated in the PTFU. Over the total 5 years, mean DAS28 was similar between groups (P > 0.20). During U-Act-Early, biologic DMARD use decreased in both TCZ initiation groups and increased in the MTX initiation group, but during follow-up this trend did not continue. SR was achieved at least once in 99% of patients. Of the 226 patients, only 30% had any radiographic progression over 5 years, without significant differences between the groups. CONCLUSION: Although in the short-term the strategies initiating TCZ yielded the most clinical benefit, in the longer-term differences in important clinical outcomes between the strategies disappeared, probably due to continuation of the treat-to-target principle.
31421936 A Minimum 5-Year Longitudinal Study of a New Total Wrist Arthroplasty in Patients With Rhe 2020 Mar PURPOSE: To evaluate the longitudinal clinical outcomes using a new semiconstrained wrist prosthesis for the treatment of severe rheumatoid arthritis of the wrist. METHODS: Twenty patients with rheumatoid arthritis (20 wrists) underwent total wrist arthroplasty with the prosthesis in a clinical trial. The preoperative Larsen classification was grade IV in 16 wrists and grade V in 4 wrists. Assessments were performed before surgery, 1.5 years after surgery, and at final follow-up (≥ 5 years after surgery) using the visual analog scale for pain, Figgie wrist score, Japanese version of the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, and plain radiographs. RESULTS: At final follow-up, no patient had wrist pain. The preoperative flexion-extension arc at final follow-up was similar to the preoperative range. The mean 1.5-year postoperative Figgie score was significantly improved and was unchanged at final follow-up. The DASH score significantly improved from before surgery to 1.5 years after surgery; the DASH score was improved further at final follow-up, but not significantly. Five of the 19 wrists evaluated had radiographic findings indicating carpal component loosening at final follow-up; however, all patients with the loosening were asymptomatic and had not undergone revision surgery. CONCLUSIONS: Total wrist arthroplasty using this wrist prosthesis leads to favorable clinical outcomes regarding pain relief and retained range of wrist motion. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.