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ID PMID Title PublicationDate abstract
32171920 Exosomes: Effectual players in rheumatoid arthritis. 2020 Jun Rheumatoid arthritis is a well-known chronic inflammatory joint disorder. It encompasses systemic inflammation, autoimmunity and development of several joint abnormalities leading to the lifelong disability and increased mortality. Exosomes are nano-sized (30-100 nm) mammalian extracellular particles with essential properties to regulate biological processes and cellular signaling by transferring protein and genetic materials. Understanding the diversity in the exosomal contents and their corresponding targets may contribute to better recognition of the processes that are implicated in the development and progression of diseases such as autoimmune disorders. Exosomes may act as a potential biomarker for the diagnosis of autoimmune disorders. In the present review, we aimed to bring together the relevant evidence on the biology of exosomes in rheumatoid arthritis, and also discuss the recent findings regarding the diagnostic, prognostic and therapeutic promise of these nanoparticles.
32764882 A critical review of the United States regulatory pathways for determining the equivalence 2020 We evaluated the appropriateness of various equivalence margins for CT-P13, an infliximab biosimilar, in the PLANETRA clinical trial. The 95-95% method was used to independently determine an equivalence margin by pooling the historical clinical trials with original infliximab versus placebo, identified in a systematic literature search. The constancy assumption with the PLANETRA trial was assessed for each identified historical clinical trial to decide which study was scientifically justifiable to be pooled. A sensitivity analysis was performed for each study-pooling scenario. As a result, we identified two historical clinical trials that were deemed appropriate, whereas the PLANETRA trial pooled three additional studies to determine an equivalence margin, which was accepted by the United States Food and Drug Administration. However, those extra clinical trials did not meet the constancy assumption in baseline characteristics, methotrexate dose, and efficacy assessment time. The clinically more appropriate equivalence margin was 5.7 percentage points, which was much narrower than the 12 percentage points applied in the approval of CT-P13. In conclusion, the equivalence claim for CT-P13 to original infliximab in patients with rheumatoid arthritis did not appear to be supported when the constancy assumption was strictly assessed. The equivalence margin for biosimilars could be determined more conservatively.
33336324 What Are the Preferences of Patients With Rheumatoid Arthritis for Treatment Modification? 2021 Sep OBJECTIVES: Optimal care of rheumatoid arthritis (RA) patients entails regular assessment of disease activity and appropriate adjustment of disease-modifying antirheumatic drugs (DMARDs) until a predefined treatment goal is achieved. This raises questions about the approach to treatment decision making among RA patients and their preference for associated treatment changes. We aimed to systematically identify and synthesize the available evidence of RA patients' preferences regarding DMARD modification with an emphasis on escalating, tapering, stopping, or switching of DMARDs. METHODS: A scoping review was undertaken to gauge the breadth of evidence from the range of studies relating to RA patients' preferences for DMARD modification. Pertinent databases were searched for relevant studies published between 1988 and 2019. Conventional content analysis was applied to generate themes about how patients perceive changes to their RA treatment. RESULTS: Of the 1730 distinct articles identified, 32 were included for review. Eight studies investigated RA patients' perceptions of switching to other DMARDs, 18 studies reported RA patients' preferences for escalating treatment, and six studies explored the possibility of tapering or stopping of biologic DMARDs. Four overarching themes relating to RA patients' preferences for treatment modification were identified: (i) patient satisfaction, (ii) patients' beliefs, (iii) information needs, and (iv) patient-clinician relationships. CONCLUSION: Uptake of treatment changes in clinical practice can be improved by understanding how RA patients approach the decision to modify their treatment and how this relates to their satisfaction, beliefs, information needs, and relationships with clinicians. Future work is needed to systematically determine the significance of these factors in RA patients' decision-making processes.
32048365 The effect of saffron supplement on clinical outcomes and metabolic profiles in patients w 2020 Jul Rheumatoid arthritis (RA) is a systemic autoimmune and inflammatory disease. Our study aimed to determine the effect of saffron supplement on clinical outcomes and metabolic profiles in patients with active RA. In this randomized, double-blind, placebo-controlled trial, 66 women older than 18 years old received 100 mg/day either saffron supplement in the intervention group (n = 33) or matched placebo in the placebo group (n = 33) for a period of 12 weeks. Sixty-one patients (30 in the control and 31 in the saffron group) remained for the final analysis. No adverse effects were reported by the patients. Saffron supplementation significantly decreased the number of tender (-1.38 ± 1.66 vs. 0.10 ± 0.40, p < .001) and swollen (-2.12 ± 2.34 vs. 0.63 ± 2.79, p < .001) joints, pain intensity based on visual analogue scale (-18.36 ± 15.07 vs. -2.33 ± 5.04), p < .001), and disease activity score (DAS28) (-0.75 ± 0.67 vs. 0.26 ± 0.77, p < .001) at the end of intervention between the two groups and in saffron group compared with baseline values. Physician Global Assessment (p = .002) and erythrocyte sedimentation rate were significantly improved after intervention (24.06 ± 12.66 vs. 32.00 ± 14.75, p = 0.028). High-sensitivity C-reactive protein reduced at the end of the intervention in the saffron group compared with baseline values (12.00 ± 7.40 vs. 8.82 ± 7.930, p = .004). Tumor necrosis factor alpha, interferon gamma, and malondialdehyde were decreased, and total antioxidant capacity were increased, but their differences between the two groups were not significant (p > .05). According to the results, saffron supplements could positively and significantly improve clinical outcomes in RA patients.
32537893 Selection and perception of methotrexate treatment information in people with rheumatoid a 2020 Jun OBJECTIVE: To determine beliefs about methotrexate (MTX) in patients with rheumatoid arthritis (RA) in relation to utilized information sources. METHODS: RA patients, who were current participants in the Australian national biologic registry, completed an online questionnaire regarding their use and views about MTX (N = 1010). Participants who used MTX were asked about which MTX information sources they consulted, and whether positive or negative views were obtained. The Beliefs about Medicine Questionnaire (BMQ), was used to measure patient beliefs about MTX. RESULTS: The survey response rate was 804/1010 (80%). MTX survey data were analyzed for 742 RA participants (mean age 59 years, 76% female, mean disease duration 19 years) who had used MTX, with 494/742 (67%) reporting current use. Participants consulted multiple information sources (median 3, interquartile range 1-5). Rheumatologists (98%), general practitioners (GPs) (55%), internet searches (39%), educational websites (38%), and pharmacists (37%) were the most common information sources utilized. Positive MTX information was most often obtained from rheumatologists (92%), GPs (66%), and educational websites (56%). Negative information was most often obtained from relatives, social media, internet chat rooms and friends. Information from rheumatologists was the most influential on favorable BMQ MTX-specific scores, whereas information from educational websites also affirmed the need for MTX. CONCLUSION: RA patients have significant concerns regarding MTX and consult a variety of sources for MTX information. However, the patient perception of this information varies widely. Rheumatologists and educational websites are the most important information sources in terms of a positive influence on the patient's perception of MTX.
32948325 Adherence to biologic disease-modifying antirheumatic drugs in adult patients with rheumat 2021 Sep INTRODUCTION: The emergence of biologics has revolutionized the management of refractory rheumatic diseases (RD) by improving clinical outcomes. Unfortunately, the impact of non-adherence to the emerging therapy can limit their potential benefit. The objective of our study was to evaluate biologics' adherence in Tunisian patients with RD and to assess the determinants of non-adherence. METHODS: We conducted a cross-sectional study involving patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) treated with bDMARDs (biologic disease-modifying antirheumatic drugs) for at least three months. Socio-demographic, clinical and biological data were collected. Biologic adherence was assessed using the compliance questionnaire for rheumatology (CQR). RESULTS: One hundred patients with RD (45 RA and 55 SpA) were collected. Non-adherence to bDMARDs was found in 70% of cases. In univariate analysis, non-adherence to bDMARDs was statistically related to the absence of coxitis (P=0.003), to a low ASDAS-CRP (ankylosing spondylitis disease activity score) prior to the initiation of the bDMARDs (P=0.01), to a rate of administration of bDMARDs less than one injection per month (P=0.01), to the subcutaneous delivery route (P=0.02) as well as to non-adherence to csDMARDs (conventional disease-modifying antirheumatic drugs) (P=0.001). In multivariate analysis, the predictors of non-adherence were the absence of coxitis (OR=6.01; IC 95% [1.88-19.12]; P=0.002], and a rate of administration of bDMARDs less than one injection per month (OR=8.79; IC 95% [2.13-36.22]; P=0.003). CONCLUSION: This work has revealed the low rate of adherence to biological treatments in Tunisian patient with RD. Predictors of poor adherence were the absence of coxitis and a rate of administration of bDMARDs less than one injection per month. Detection of these factors could help us to adapt our strategies to improve adherence that are essentially based on therapeutic education program.
33257093 Impact of a risk-sharing agreement in rheumatoid arthritis in Spain. 2021 Mar CONTEXT AND OBJECTIVE: Risk-sharing agreements(RSA) allow decision-makers to manage the uncertainty associated with effectiveness and costs of treatments. Our objective was to estimate the economic impact of RSA implementation on treatment of patients diagnosed with rheumatoid arthritis(RA) with certolizumab pegol(CZP) and assess the potential impact of alternative RSA. METHODS: Under original RSA, treatment with CZP was reimbursed when the response was optimal (DAS28 score <3.2) or satisfactory (DAS28 score ≥3.2 and reduction from baseline ≥1.2) at 12 weeks. Alternative RSA would additionally include a 50 % reimbursement for moderate responders(DAS28 score >3.2 and ≤5.1, and reduction from baseline between 0.6 and 1.2). We estimated average savings per patient for hospital's pharmacy service(HPS) at 12 weeks, taking into account the pharmacological cost of CZP. Uncertainty associated with effectiveness of CZP was assessed through 1000 Monte Carlo simulations. RESULTS: After 12 weeks of treatment, 57.8 % (n = 52) and 22.2 %(n = 20) of patients had optimal and satisfactory responses, respectively, and average disease activity improved by 1.77 points. Average savings for HPS amounted to 876.9€ and 706.4€ per patient under original and alternative RSA, respectively. Savings in simulated cohort reached 846.2€ and 681.8€ per patient, respectively, leading to estimated net savings for HPS of 846,209€ and 681,790€, respectively. CONCLUSIONS: RSA implementation on patients with RA treated with CZP has generated savings and improved efficiency within HPS.
32946265 Proarrhythmic electrophysiological and structural remodeling in rheumatoid arthritis. 2020 Nov 1 Chronic inflammatory disorders, including rheumatoid arthritis (RA), are associated with a twofold increase in the incidence of sudden cardiac death (SCD) compared with the healthy population. Although this is partly explained by an increased prevalence of coronary artery disease, growing evidence suggests that ischemia alone cannot completely account for the increased risk. The present review explores the mechanisms of cardiac electrophysiological remodeling in response to chronic inflammation in RA. In particular, it focuses on the roles of nonischemic structural remodeling, altered cardiac ionic currents, and autonomic nervous system dysfunction in ventricular arrhythmogenesis and SCD. It also explores whether common genetic elements predispose to both RA and SCD. Finally, it evaluates the potential dual effects of disease-modifying therapy in both diminishing and promoting the risk of ventricular arrhythmias and SCD.
32896260 Rheumatoid arthritis patients with low baseline Health Assessment Questionnaire scores hav 2020 Nov OBJECTIVES: To determine prognostic factors for the Health Assessment Questionnaire-Disability Index (HAQ-DI) progression in patients with rheumatoid arthritis (RA) in clinical practice. METHODS: We evaluated 388 biological disease-modifying anti-rheumatic drug (bDMARD)-naïve Japanese patients with RA with moderate to high disease activity at study entry after being treated with conventional synthetic DMARDs. These patients were treated according to a treat-to-target (T2T) strategy for one year. The Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the HAQ-DI were assessed every three months. We also evaluated joint destruction using a modified total Sharp score at baseline and at one year. HAQ-DI progression was defined as the yearly progression of HAQ-DI >0.1. We performed a multiple logistic regression analysis to explore the factors predicting HAQ-DI progression at one year. RESULTS: HAQ-DI progression was observed in 18% of the patients. The multiple logistic regression analysis revealed the independent variables associated with HAQ-DI progression were: DAS28-ESR >5.1 at baseline (odds ratio [OR] 0.31, 95% con dence interval [CI] 0.13-0.74, p=0.0083); HAQ-DI score at baseline <0.5 (OR 2.27, 95% CI 1.22-4.26, p=0.0102); and achievement of low disease activity at 12 weeks (OR 0.42, 95% CI 0.21-0.82, p=0.0112). CONCLUSIONS: Our data suggest that maintaining clinical improvement according to T2T and initiating the treatment at an early stage are important for functional improvement after one year and that patients with low baseline HAQ scores have a higher risk of HAQ disability progression.
33189451 Hypothesis: Rheumatoid arthritis and periodontitis: A new possible link via prolactin horm 2021 Jan Rheumatoid arthritis and periodontitis are two common chronic inflammatory diseases affecting human population worldwide. The association between the two conditions have been the focus of many researches, trying to explore the possible mechanisms underlying this association. Prolactin hormone, besides its known lactogenic effects acts as a cytokine secreted from various tissues other than the pituitary gland with multiple pleotropic actions in immunity and inflammation. Several data showed that prolactin levels are increased significantly in the synovial and periodontal tissues, and this increase is correlated with disease activity and tissue destruction. Our hypothesis suggests that local prolactin can represent a link between the two conditions. In this work, we suggest a possible mechanistic interactions, hypothesized to form a common path linking between rheumatoid arthritis, periodontitis and prolactin. This is because of the need to develop new treatment strategies for the most effective long term control of inflammation in both conditions.
32371020 Cortical thickness relative to the transverse diameter of third metacarpal bone reflects b 2020 Aug OBJECTIVE: Rheumatoid arthritis (RA) is accompanied by potential risk of bone mineral loss. In this study, we developed a screening index for the osteoporosis related level of bone mineral density loss for RA patients as a substitute to the dual-energy X-ray absorptiometry (DXA) method. METHODS: X-ray pictures of both sides of the hand were taken in order to evaluate Sharp/van der Heijde Scores (SHSs). This score was calculated for RA patients at the first consultation and routinely thereafter. We measured cortical thickness and the transverse diameter of the mid-portion of the metacarpal bone of the right middle finger with the same radiograph. Cortical Thickness Ratio (CTR) was then calculated as cortical thickness relative to the transverse diameter. Bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN) was measured at the same time. The relationship between BMD and CTR was evaluated using multivariate linear regression analysis. Clinical backgrounds and disease indices were also evaluated. The cut-off index (COI) of the CTR for osteoporosis criteria that represented with a T-score < -2.5 for both bones was calculated using the Receivers Operation Characteristics technique. RESULTS: In 300 subjects, the CTR demonstrated significant correlation with BMD in both bones (p < 0.01). The COI was determined to be 0.25 and the odds ratio was 4.19 and 4.90 for the LS and FN, respectively. CONCLUSION: Our findings indicated that the CTR correlated with BMD. This index may represent a promising screening tool for the judgment of osteoporosis in RA patients.
32645358 Natural products action on pathogenic cues in autoimmunity: Efficacy in systemic lupus ery 2020 Oct Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by self-perpetuating inflammation and tissue/organ damage, resulting from the failure of lymphocyte auto-tolerance, cause morbidity and mortality worldwide. The current drugs or therapies including conventional non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), as well as several biologic therapies such as B cell-targeted, T cell-targeted, cytokines-targeted and cytokines receptors-targeted therapy, cannot completely cure SLE and RA, and are always accompanied by unexpected side effects. Therefore, more studies have explored new methods for therapy and found that the herbal medicine as well as its natural products (NPs) exhibited promising therapeutic value through exerting effects of immunomodulation, anti-inflammation, anti-oxidation, and anti-apoptosis, etc. via regulating abnormal responses in kidney, innate and adaptive immune systems, intestine, synoviocytes, as well as bone system including chondrocytes, osteoclasts, joints and paw tissues. In the present review, we will elucidate the current mainstream drugs and therapies for SLE and RA, and summarize the efficacy and mechanisms of NPs in the treatment of SLE and RA based on available findings including in vitro and in vivo animal models, as well as clinical studies, and further analyze the existing challenges, in order to provide comprehensive evidence for improvement of SLE and RA therapy by NPs and to promote management of these two autoimmune diseases.
30098882 Expert Recommendations on the Interleukin 6 Blockade in Patients with Rheumatoid Arthritis 2020 Jul OBJECTIVE: To draft recommendations on interleukin 6 (IL-6) blockade in rheumatoid arthritis (RA), based on best evidence and experience. METHODS: A group of 10 experts on IL-6 blockade in RA was selected. The 2 coordinators formulated 23 questions about IL-6 blockade (indications, efficacy, safety, etc.). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (Medline, EMBASE and the Cochrane Library were searched). Two different reviewers selected the articles. Evidence tables were created. At the same time, European League Against Rheumatism and American College of Rheumatology abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted on in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Centre for Evidence Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). RESULTS: The 8 preliminary recommendations were accepted after the Delphi process. They covered aspects such as the use of these therapies in monotherapy, in combination, in patients with refractory disease or intolerant patients, response evaluation, optimization and risk management. CONCLUSIONS: The manuscript aims to solve frequently asked questions and aid in decision making strategies when treating RA patients with IL-6 blockade.
31430553 The association between genetic polymorphisms of interleukin 23 receptor gene and the risk 2020 Jan This meta-analysis was conducted to confirm whether seven single nucleotide polymorphisms (SNPs) of interleukin-23 receptor (IL23R) gene are associated with rheumatoid arthritis (RA) susceptibility. RevMan version 5.3 was used to calculate statistical data. Sixteen articles involving 11,816 RA patients and 14,268 healthy controls were included in this meta-analysis. A significant association was identified between the rs11209026 polymorphism and RA susceptibility in Caucasians (AA vs. GG: OR = 1.78, 95% CI = 1.02-3.10, P = .04; AA vs. AG + GG: OR = 1.77, 95% CI = 1.02-3.08, P = .04). Additionally, our result showed that the G allele of IL23R/rs10489629 had a significantly increased frequency in RA patients of Caucasians and Asians (A vs. G: OR = 0.92, 95% CI = 0.88-0.97, P = .002; OR = 0.62, 95% CI = 0.44-0.87, P = .006, respectively). Furthermore, the meta-analysis revealed a significant association between the rs1343151 polymorphism and RA susceptibility in Caucasians (C vs. T: OR = 0.91, 95% CI = 0.87-0.96, P = .0004). Our meta-analysis confirmed the IL23R gene might be treated as a susceptible factor for RA.
33225988 Presence of salivary IgA anti-citrullinated protein antibodies associate with higher disea 2020 Nov 23 BACKGROUND: Circulating IgA anti-citrullinated protein antibodies (ACPA) associate with more active disease, but a previous study implied that salivary IgA ACPA is related to a less severe disease. Therefore, we aimed to characterize the IgA ACPA response in the saliva and serum in relation to clinical picture and risk factors among patients with rheumatoid arthritis (RA). METHODS: RA patients (n = 196) and healthy blood donors (n = 101), included in the cross-sectional study "Secretory ACPA in Rheumatoid Arthritis" (SARA), were analyzed for ACPA of IgA isotype, and for subclasses IgA1 and IgA2 ACPA in paired saliva and serum samples using modified enzyme-linked immunosorbent assays (ELISA) targeting reactivity to a cyclic citrullinated peptide (anti-CCP). Cutoff levels for positive tests were set at the 99th percentile for blood donors. Antibody levels were related to clinical characteristics, radiographic damage, smoking habits, and carriage of HLA-DRB1/shared epitope (SE). RESULTS: IgA ACPA in the saliva was found in 12% of RA patients, IgA1 occurred in 10%, and IgA2 in 9%. In serum, IgA ACPA was found in 45% of the patients, IgA1 in 44%, and IgA2 in 39%. Levels of IgA ACPA in the saliva correlated significantly with serum levels of IgA (r = 0.455). The presence of salivary IgA ACPA was associated with a higher erythrocyte sedimentation rate (ESR), 28-joint disease activity score, tender joint count, and patient global assessment at the time of sampling. None of the antibodies was associated with smoking, SE, or radiographic damage. CONCLUSION: Salivary IgA ACPAs were detected in a subset of RA patients in association with higher disease activity. This suggests that mucosal ACPA responses in the oral cavity may contribute to disease-promoting processes in RA.
32734446 Comparative study between human mesenchymal stem cells and etanercept as immunomodulatory 2020 Oct To compare human adipose tissue mesenchymal stem cells (AT-MSCs) and etanercept as immunomodulatory agents for collagen-induced arthritis (CIA). CIA was induced by rats' immunization with collagen type II (CII) in complete Freund's adjuvant in days 0 and 7. Before the onset of CIA, prevention group received five doses of AT-MSCS intraperitoneally. After establishment of arthritis, rats received either five doses of AT-MSCs or phosphate-buffered saline (PBS) intraperitoneally or six doses of etanercept subcutaneously. Clinical and histopathological evaluation were performed in all groups; serum levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and anti-collagen II were assessed by enzyme-linked immunosorbent assay (ELISA). A total percent of autoreactive T and regulatory T (Treg) cells were quantified using spleen immune histochemical analysis. AT-MSCs were able to delay the onset of CIA, suppress the ongoing clinical and histopathological signs, decrease serum levels of TNF-α and anti-collagen type II, and downregulate the autoreactive T cells as etanercept. AT-MSCs were more potent in Treg cells upregulation, producing high serum levels of IL10. AT-MSCs might have a therapeutic effect in CIA via their potency in immune cell education, representing an effective new promising approach in rheumatoid arthritis in human.
32270591 Patient and clinician perspectives on a patient-facing dashboard that visualizes patient r 2020 Aug BACKGROUND: Poor patient-clinician communication around patient-reported outcomes (PROs) is a barrier to the effective management of rheumatoid arthritis (RA). We aimed to develop an RA 'dashboard' that could facilitate conversations about PROs and that would be acceptable to a wide range of patients, including English and Spanish speakers and patients with adequate or limited health literacy. METHODS: A diverse group of RA patients along with clinicians from two academic rheumatology clinics joined separate focus groups. We solicited feedback and made iterative changes to mock-ups of an RA dashboard that visualized PROs using a human-centred design process. We used the thematic analysis method to identify and characterize themes from the focus groups and used these insights to refine the dashboard. RESULTS: We conducted six focus groups involving 25 RA patients and three groups with 11 clinicians. Patients and clinicians agreed that the dashboard could enhance communication about PROs and RA disease activity and could promote patient self-management. Patients varied in their (a) comprehension, (b) preferences for the display and features of the dashboard, and (c) desired uses for the dashboard. Clinicians expressed significant concerns about the logistics of using the dashboard in clinical practice. CONCLUSION: Using principles of human-centred design, we created an RA dashboard that was well-accepted among patients and clinicians. The ability to customize the data display is important for tailoring the dashboard to patients with diverse needs and preferences. Special attention should be given to feasibility concerns voiced by clinicians.
31451935 Nailfold capillaroscopy and autoimmune connective tissue diseases in patients from a Portu 2020 Feb Raynaud's phenomenon (RP) is frequent in autoimmune connective tissue diseases (AICTD) and its approach includes nailfold capillaroscopy (NFC), as it is a non-invasive technique that permits direct visualization of the microcirculation. The aim of this study is to analyze and establish clinical correlations between NFC findings and particular aspects of autoimmune disorders. This is a retrospective study. Clinical data from patients attending our NFC clinic were reviewed. Inclusion criteria included AICTD previous diagnosis, which included systemic sclerosis (SSc), mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), Sjögren syndrome, inflammatory idiopathic myopathies (IIM), rheumatoid arthritis, undifferentiated connective tissue disease and antiphospholipid syndrome (APS). Videocap(®) version 3.0 biomicroscope was used. NFC score was determined. For statistics, SPSS software was utilized. 384 patients were included; most of them were women, with mean age of 47 years. RP was present in 91% of the patients, with greater prevalence in SSc and MCTD. Scleroderma pattern was the most prevalent NFC pattern, mainly in SSc, MCTD and IIM. Mean capillary density was reduced in IIM, SSc and MCTD. NFC score was worse in SSc, IIM and MCTD. In patients with AICTD, RP is related to microvascular damage and worse NFC score. NFC scleroderma pattern correlates with SSc classification criteria score. In MCTD, scleroderma pattern relates to myositis. SLE and APS reveal significant hemorrhages, but not related to APS antibodies. This study highlights the possible role of NFC as biomarker of AICTD, particularly in SSc and IIM.
31958282 ​Risk of major adverse cardiovascular events among patients with rheumatoid arthritis af 2020 Jan OBJECTIVE: Rheumatoid arthritis (RA) is a known risk factor for developing coronary artery disease (CAD). The influence of RA on the prognosis after initial CAD diagnosis and treatment is however largely unknown. We examined the risk of major cardiovascular events among RA and non-RA patients with chest pain referred to cardiac CT. METHODS: This was a follow-up study, using data from the Western Denmark Heart Registry, containing data on CT angiography examinations (Cardiac CT). Information on RA diagnosis and covariates were identified through nationwide administrative registers. The primary outcome was a combined outcome including, myocardial infarction, ischaemic or unspecified stroke, coronary artery bypass grafting, percutaneous coronary intervention, and all-cause mortality. Median time until events or censoring was 3.5 years (min/max: 0.0: 9.2). Cox proportional hazard models were used to examine the association between RA/non-RA patients and outcomes. RESULTS: Among 42 257 patients, referred between 2008 and 2016, we identified 358 (0.8%) with RA. An increased risk was seen in RA compared with non-RA (adjusted HR 1.35, 95% CI 0.93 to 1.96). Among patients who had received flare treatment more than once prior to cardiac CT the adjusted HR 1.80 (95% CI 1.08 to 3.00), and among patients with seropositive RA the adjusted HR 1.42 (95% CI 0.93 to 2.16). CONCLUSION: In patients referred to cardiac CT due to chest pain, we found a trend of an association between RA and the combined primary outcome, supporting that RA per se, but in particular seropositive and active RA, may increase the risk of CAD even after initial CAD diagnosis and treatment.
32363771 Population pharmacokinetics of adalimumab biosimilar adalimumab-adbm and reference product 2020 Nov AIMS: Adalimumab-adbm is a monoclonal antibody developed as a biosimilar to adalimumab (Humira, AbbVie Inc.). The key objectives of this study were using a population pharmacokinetic (PPK) approach to assess pharmacokinetic (PK) similarity between adalimumab-adbm and Humira in patients with active rheumatoid arthritis (RA), to quantify the effects of potential covariates on adalimumab PK and to assess the impact of switching treatment from Humira to adalimumab-adbm on PK. METHODS: A PPK model was firstly developed using intensive PK data from the phase-1 study in healthy subjects (NCT02045979). PPK models were developed separately for phase-3 base study (NCT02137226) and its extension study (NCT02640612) in patients with active RA. RESULTS: PPK models were developed for adalimumab from adalimumab-adbm and Humira treatment in healthy subjects and RA patients. Weight and anti-drug antibodies were found to be important predictors of adalimumab clearance. Adalimumab PK was similar between adalimumab-adbm and Humira. The estimated effect of Humira on clearance, relative to the adalimumab-adbm, was 1.02 (i.e., Humira has 0.02 greater clearance). Similarly, the effect of treatment arms (switching) on clearance was estimated to be 1.00 and 0.997 for Humira:Humira:BI and Humira:BI:BI arms, respectively, relative to the BI:BI:BI arm (BI refers to adalimumab-adbm) in the phase-3 extension study. CONCLUSION: PK similarity between adalimumab-adbm and Humira in patients with active RA was demonstrated using PPK approach. Adalimumab PK was also similar when switching treatment from Humira to adalimumab-adbm at either week 24 or 48.