Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
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32735158 | Anti-TNF biosimilars in rheumatology: the end of an era? | 2021 Jan | INTRODUCTION: Tumor necrosis factor inhibitors (TNFi) have revolutionized the treatment of rheumatic diseases. Whilst extremely efficacious, the original TNFi also carried a high acquisition cost that limited their use. 'Biosimilar' TNFi's, developed on expiry of the patents for the biooriginators, have comparable efficacy and safety, are less expensive and provide the potential to improve access to these effective therapies in a more cost-effective manner. AREAS COVERED: The background and development of TNFis, their biosimilars and follow on 'copycat' drugs are discussed, together with their use in both developed and developing countries, focusing on the potential to enhance access to effective targeted therapies. EXPERT OPINION: Bridging the economic gap to facilitate universal access to anti-TNF biosimilars has been largely unsuccessful, driving the development of copycat mimics in developing countries. Meanwhile, the more recent introduction of targeted synthetic disease-modifying drugs has provided cheaper, equally effective treatments for rheumatic diseases that are conveniently delivered by mouth. We review the TNF biosimilars in rheumatic diseases, their role in a rapidly evolving treatment landscape, and speculate about the future for this iconic therapeutic class. | |
31496278 | Analysis of bioactive components and pharmacokinetics of Caulophyllum robustum in rat plas | 2021 Mar | A UPLC-MS/MS method was developed and validated the determination and pharmacokinetic study of magnoflorine, cauloside C, hederagenin, and oleanolic acid from Caulophyllum robustum. Digoxin was used as the internal standard. The pretreated plasma samples were carried out on a Waters ACQUITYUPLC HSS T3 column at 35 °C with a mobile phase of acetonitrile-water (90:10, v/v) at a flow rate of 0.2 mL/min. This article describes the most simple, sensitive, and validated UPLC-MS/MS method to date for the simultaneous successful determination of four compounds in rat plasma after oral administration of the extract of C. robustum and their pharmacokinetic studies. | |
34940570 | Metabolomics in Autoimmune Diseases: Focus on Rheumatoid Arthritis, Systemic Lupus Erythem | 2021 Nov 29 | The metabolomics approach represents the last downstream phenotype and is widely used in clinical studies and drug discovery. In this paper, we outline recent advances in the metabolomics research of autoimmune diseases (ADs) such as rheumatoid arthritis (RA), multiple sclerosis (MuS), and systemic lupus erythematosus (SLE). The newly discovered biomarkers and the metabolic mechanism studies for these ADs are described here. In addition, studies elucidating the metabolic mechanisms underlying these ADs are presented. Metabolomics has the potential to contribute to pharmacotherapy personalization; thus, we summarize the biomarker studies performed to predict the personalization of medicine and drug response. | |
34912747 | Mixed Cryoglobulinaemia Vasculitis Treated with Obinutuzumab in a Patient Allergic to Ritu | 2021 | Cryoglobulinaemia is defined as the presence of cryoglobulins in the serum, which are immunoglobulins that reversibly precipitate and form a gel when the temperature is <37ºC. Autoimmune diseases such as Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis could be associated with mixed cryoglobulinaemia vasculitis (MCV). The treatment of MCV generally consists of glucocorticoids, cytotoxic agents such as cyclophosphamide, plasmapheresis or anti-CD20 monoclonal antibodies including rituximab. Here, we present a case of a 60-year-old woman who developed type II MCV in the context of overlap autoimmune disease and who has been treated with a new anti-CD20 agent, obinutuzumab. LEARNING POINTS: Mixed cryoglobulinaemia can occur in the context of autoimmune diseases such as Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis.The treatment generally consists of glucocorticoids, cytotoxic agents such as cyclophosphamide, plasmapheresis or anti-CD20 monoclonal antibodies including rituximab.New generations of humanized anti-CD20 monoclonal antibodies such as obinutuzumab have been developed to increase complement-dependent cytotoxicity and/or antibody-dependent cellular cytotoxicity, while limiting immunogenicity. These new optimized B-cell depletion strategies could be very interesting and useful in autoimmune disease treatment. | |
34632553 | Surgical resection of a rapidly growing pulmonary spindle cell carcinoma by robot-assisted | 2021 Oct 10 | BACKGROUND: Pulmonary spindle cell carcinoma (PSCC) is an extremely rare tumor that is highly malignant and fast-growing. As chemotherapy and radiation therapy are ineffective, early surgical resection is effective for PSCC. CASE PRESENTATION: A 70-year-old woman with rheumatoid arthritis was referred to our hospital with an abnormal shadow. Chest computed tomography revealed a 33-mm-wide lobular mass in the right upper lobe. She was diagnosed with non-small cell lung cancer by bronchoscopic smear cytology. Although staging evaluation indicated stage IIIB (T3N2M0) disease, she required continued administration of immunosuppressants and prednisolone for rheumatoid arthritis. Therefore, robot-assisted thoracoscopic surgery (RATS) right upper lobectomy followed by lymph node dissection was performed without preoperative chemotherapy and radiotherapy. Pathological findings revealed PSCC. CONCLUSIONS: We report a very rare case of pulmonary spindle cell carcinoma, successfully resected with RATS. | |
34596032 | The erratic C-reactive protein: a novel outcome measure for longitudinal disease activity | 2021 Sep 21 | OBJECTIVES: There is a relationship between both the magnitude and variability of C-reactive protein (CRP) levels and disease activity level in rheumatoid arthritis (RA). It seems that CRP levels remain low and stable in clinical remission then increase and become erratic in active disease. The purpose of this research was to determine if there is a difference in the variability of CRP levels over time in patients in clinical remission versus those with active disease. METHODS: Patients with a diagnosis of RA with a minimum of 3 CRP readings in the previous 12-month period were included at a single site. At each visit the patient was evaluated by an experienced rheumatologist to determine current disease activity - remission versus active disease. The primary outcome measure was the difference between the coefficient of variation of the CRP (CRP-COV) in patients in remission versus those with active disease. RESULTS: 272 patients were enrolled into the study. The mean CRP and CRP-COV was significantly smaller for patients in clinical remission versus active disease, for patients in CDAI remission (<2.6), and for those who did not require a change in treatment. Smokers, on average, had higher mean CRP readings regardless of clinical status. CONCLUSIONS: We have identified a new clinical outcome measure of disease activity in RA that captures longitudinal variability in disease activity and identifies those patients with clinically active disease despite a "normal" CRP level due to the higher variability of CRP if not in remission. | |
34283371 | Role of Myeloid-derived suppressor cell (MDSC) in autoimmunity and its potential as a ther | 2021 Oct | Myeloid suppressor cells (MDSCs) are an important class of immune-regulating cells that can suppress T cell function. Most of our knowledge about the function of MDSC comes from studies of cancer models. Recent studies, however, have greatly contributed to the description of MDSC involvement in autoimmune diseases. They are known as a cell population that may negatively affect immune responses by regulating the function of CD4(+) and CD8(+) cells, which makes them an attractive target for autoimmune diseases therapy. However, many questions about MDSC activation, differentiation, and inhibitory functions remain unanswered. In this study, we have summarized the role of MDSCs in various autoimmune diseases, and the potential of targeting them for therapeutic benefits has been discussed. | |
34003926 | Precision medicine in autoimmune diseases: fact or fiction. | 2021 Sep 1 | Much is said about precision medicine, but its real significance and potential are far from certain. Several studies in each of the autoimmune diseases have provided important insights into molecular pathways, but the use of molecular studies, particularly those looking into transcriptome pathways, has seldom approached the possibility of using the data for disease stratification and then for prediction, or for diagnosis. Only the type I IFN signature has been considered for therapeutic purposes, particularly in the case of SLE. This review provides an update on precision medicine, on what can be translated into clinical practice and on what single-cell molecular studies contribute to our knowledge of autoimmune diseases, focusing on a few examples. The main message is that we should try to move from precision medicine of established diseases to preventive medicine in order to predict the development of disease. | |
34144533 | Medicinal Plants and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Treatment of Arthrit | 2021 Jun 18 | CONTEXT: Arthritis is an inflammatory disease of diarthrodial joints and is associated with swollen inflamed joints, disruption of joints, and loss of integrity of articular cartilage and synovial joints. OBJECTIVE: The current review intended to examine the data on the epidemiology, causes, clinical diagnosis, and prevention and control of different types of arthritis and on the use of medicinal plants in gouty arthritis. DESIGN: The research team performed a literature review, searching relevant literature databases, including bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, and PubMed. The search terms were arthritis, diarthodial joints, use of medicinal plants in gouty arthritis, and synovial joints. SETTING: The study took place in the main library of the University of Sargodha in Sargodha, Pakistan. RESULTS: The research team identified 135 studies, and eventually 92 unique academic publications were included in the analysis. Arthritis can develop and progress in any musculoskeletal joint, and most commonly occurs in knees, hips, shoulders, and hands. Major risk factors for arthritis include age, obesity, trauma, other diseases, and smoking. Arthritis is classified into various types, including rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis, septic arthritis, and psoriatic arthritis (PsA). RA and OA are the most common types worldwide. RA is an autoimmune disease in which the body's immune cells attack the joints. OA develops due to damage of cartilage, tissues, and joints due to age, obesity, or stress on joints. Gouty arthritis develops due to hyperuricemia; deposits of monosodium urate crystals can lead to gouty arthritis. Septic arthritis occurs due to a microbial infection in synovial joints because in synovial joints the basement membrane is absent. PsA develops due to the psoriasis-skin disease. CONCLUSIONS: The current review showed that different types of arthritis has different causes and pathogeneses. Pain in joints is a major and common symptom in all types of arthritis. Arthritis is managed pharmacologically and nonpharmacologically. Treatment is different for each class of arthritis according to its cause and symptoms. | |
34376145 | Comparison of prevalence and exposure-disease associations using self-report and hospitali | 2021 Aug 10 | BACKGROUND: Although many studies have investigated agreement between survey and hospitalization data for disease prevalence, it is unknown whether exposure-chronic disease associations vary based on data collection method. We investigated agreement between self-report and administrative data for the following: 1) disease prevalence, and 2) the accuracy of self-reported hospitalization in the last 12 months, and 3) the association of seven chronic diseases (rheumatoid arthritis, hypertension, heart attack, stroke, asthma, diabetes, hyperlipidemia) with four measures of 9/11 exposure. METHODS: Enrollees of the World Trade Center Health Registry who resided in New York State were included (N = 18,206). Hospitalization data for chronic diseases were obtained from the New York State Planning and Research Cooperative System (SPARCS). Prevalence for each disease and concordance measures (kappa, sensitivity, specificity, positive agreement, and negative agreement) were calculated. In addition, the associations of the seven chronic diseases with the four measures of exposure were evaluated using logistic regression. RESULTS: Self-report disease prevalence ranged from moderately high (40.5% for hyperlipidemia) to low (3.8% for heart attack). Self-report prevalence was at least twice that obtained from administrative data for all seven chronic diseases. Kappa ranged from 0.35 (stroke) to 0.04 (rheumatoid arthritis). Self-reported hospitalizations within the last 12 months showed little overlap with actual hospitalization data. Agreement for exposure-disease associations was good over the twenty-eight exposure-disease pairs studied. CONCLUSIONS: Agreement was good for exposure-disease associations, modest for disease prevalence, and poor for self-reported hospitalizations. Neither self-report nor administrative data can be treated as the "gold standard." Which source to use depends on the availability and context of data, and the disease under study. | |
34563686 | Chikungunya and arthritis: An overview. | 2021 Nov | Chikungunya is caused by CHIKV (chikungunya virus), an emerging and re-emerging arthropod-vectored viral infection that causes a febrile disease with primarily long term sequelae of arthralgia and myalgia and is fatal in a small fraction of infected patients. Sporadic outbreaks have been reported from different parts of the world chiefly Africa, Asia, the Indian and Pacific ocean regions, Europe and lately even in the Americas. Currently, treatment is primarily symptomatic as no vaccine, antibody-mediated immunotherapy or antivirals are available. Chikungunya belongs to a family of arthritogenic alphaviruses which have many pathophysiological similarities. Chikungunya arthritis has similarities and differences with rheumatoid arthritis. Although research into arthritis caused by these alphaviruses have been ongoing for decades and significant progress has been made, the mechanisms underlying viral infection and arthritis are not well understood. In this review, we give a background to chikungunya and the causative virus, outline the history of alphavirus arthritis research and then give an overview of findings on arthritis caused by CHIKV. We also discuss treatment options and the research done so far on various therapeutic intervention strategies. | |
34594409 | Frequent injections of high-dose human umbilical cord mesenchymal stem cells slightly aggr | 2021 Nov | A single injection of low-dose human umbilical cord-derived mesenchymal stem cells (UC-MSCs) has been previously demonstrated to relieve synovitis and bone erosion in animal models of arthritis, but whether frequent injections of high-dose UC-MSCs relieve arthritis and inhibit loss of muscle mass has remained elusive. In the present study, DBA/1 mice were randomly divided into three groups: Normal (wild-type mice; n=11), collagen-induced arthritis (CIA; n=12) and CIA treated with UC-MSCs (n=11; 5x10(6) UC-MSCs per week for 3 weeks). Arthritis and skeletal muscle cachexia were evaluated until the end of the experiment on day 84. It was indicated that both the CIA and UC-MSC groups had lower body weights compared with the normal mice. Clinical arthritis scores, hind ankle diameters, synovitis and bone erosion progressively increased and were similar between the CIA and UC-MSC groups. Although there was no difference in food intake among the three groups, the normalized food intake of normal group was significantly higher than CIA group and UC-MSC group from day 42 onwards; there was no significance on day 77 but this could be neglected. Furthermore, gastrocnemius muscle weight in the UC-MSC group was significantly reduced compared with that in the CIA and normal groups. The UC-MSC group had higher levels of proinflammatory cytokines, such as TNF-α, IL-6 and IL-1β than those in the CIA group. However, the other cytokines assessed and the fibrosis indices in the CIA and UC-MSC groups were not different from those in the control group and there was no inflammatory cell infiltration. Thus, frequent injections of high-dose UC-MSCs slightly aggravated synovitis and muscle cachexia in the murine CIA model and should therefore be avoided in the treatment of arthritis. | |
33547063 | Tenosynovitis has a high sensitivity for early ACPA-positive and ACPA-negative RA: a large | 2021 Feb 5 | OBJECTIVES: Clinically evident tenosynovitis can be seen in established rheumatoid arthritis (RA). Imaging research has recently shown that tenosynovitis at small joints occurs in early RA, contributes to typical RA symptoms (including joint swelling) and is infrequent in healthy controls. Imaging-detectable tenosynovitis is often not recognisable at joint examination, hence its prevalence can therefore be underestimated. We hypothesised that if MRI-detectable tenosynovitis is a true RA feature, the sensitivity for RA is high, in both anti-citrullinated protein antibodies (ACPA)-positive and ACPA-negative RA, and lower in other diseases that are associated with enthesitis (such as spondyloarthritis (SpA) and psoriatic arthritis (PsA)). So far, no large MRI study addressed these questions. METHODS: Consecutive patients with early arthritis (n=1211) from one healthcare region underwent contrast-enhanced 1.5T MRI of hand and foot at diagnosis. MRIs were scored for synovitis and tenosynovitis by two readers blinded for clinical data. All included patients with ACPA-positive RA (n=250), ACPA-negative RA (n=282), PsA (n=88), peripheral SpA (n=24), reactive arthritis (n=30) and self-limiting undifferentiated arthritis (UA; n=76) were studied. Sensitivity was calculated. RESULTS: The sensitivity of tenosynovitis in RA was 85%; 88% for ACPA-positive RA and 82% for and ACPA-negative RA (p=0.19). The sensitivity for RA was significantly higher than for PsA (65%; p=0.001), SpA (53%; p<0.001), reactive arthritis (36%; p<0.001) and self-limiting UA (42%; p<0.001). The observed sensitivity of MRI synovitis was 91% in RA and ranged from 83% to 54% in other groups. CONCLUSIONS: MRI-detected tenosynovitis has a high sensitivity for early ACPA-positive and ACPA-negative RA. This supports that both juxta-articular (tenosynovitis) and intra-articular synovial involvement is characteristic of RA. | |
33498217 | DGEMRIC in the Assessment of Pre-Morphological Cartilage Degeneration in Rheumatic Disease | 2021 Jan 20 | BACKGROUND: Even though cartilage loss is a known feature of psoriatic (PsA) and rheumatoid arthritis (RA), research is sparse on its role in the pathogenesis of PsA, its potential use for disease monitoring and for differentiation from RA. We therefore assessed the use of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) to evaluate biochemical cartilage changes in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints in PsA patients and compared these to RA patients. MATERIALS AND METHODS: A total of 17 patients with active PsA and 20 patients with active RA were evaluated by high-resolution 3 Tesla dGEMRIC using a dedicated 16-channel hand coil. Images were analyzed by two independent raters for dGEMRIC indices and joint space width (JSW) at MCP and PIP joint levels. RESULTS: No significant differences of dGEMRIC values could be found between both study populations (PsA 472.25 ms, RA 461.11 ms; p = 0.763). In all RA and most PsA patients, PIP joints showed significantly lower dGEMRIC indices than MCP joints (RA: D2: p = 0.009, D3: p = 0.008, D4: p = 0.002, D5: p = 0.002; PsA: D3: p = 0.001, D4: p = 0.004). Most joint spaces had similar widths in both disease entities and no significant differences were found. CONCLUSIONS: As evaluated by dGEMRIC, the molecular composition of the MCP and PIP joint cartilage of PsA patients is similar to that of RA patients, demonstrating the scientific and clinical feasibility of compositional magnetic resonance (MR) imaging in these disease entities. Patterns and severity of compositional cartilage degradation of the finger joints may therefore be assessed beyond mere morphology in PsA and RA patients. | |
34432308 | Incidence, prevalence, and predictors of inflammatory arthritis in patients with hidradeni | 2021 Aug 25 | An increasing amount of evidence has emerged suggesting that hidradenitis suppurativa (HS) is associated with inflammatory arthritis. This study reviewed the incidence, prevalence, and predictors of inflammatory arthritis in patients with HS. A comprehensive literature search was conducted in CINAHL, Embase, and Medline from inception to February 14, 2020. Articles were included in the review if they provided data on disease epidemiology or predictors of adult or pediatric HS patients with comorbid inflammatory arthritis. There are no validated diagnostic criteria for HS, thus we considered patients as having HS if they had at least one diagnostic code in a hospital or claims database or a diagnosis of HS/inflammatory arthritis in a medical record. The same criteria were used to confirm presence of inflammatory arthritis. We identified an increased incidence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in HS patients when compared with estimates in the general population. We identified a relatively high prevalence of RA, spondyloarthritis (SpA), and PsA in HS patients when compared with estimates in the general population. There was evidence to suggest that patients who are younger than 30, male, have severe HS, or are taking infliximab or adalimumab (which may also be confounded by HS disease severity) may be at greater risk for specific subtypes of inflammatory arthritis. However, further data are needed to confirm these associations. The increased incidence and prevalence of inflammatory arthritis within HS patients underscore the need for increased awareness and interdisciplinary partnership within rheumatology and dermatology. | |
34883551 | Two-year clinical outcomes after discontinuation of long-term golimumab therapy in Korean | 2021 Dec 13 | BACKGROUND/AIMS: The aim of this study was to investigate long-term post-discontinuation outcomes in patients with rheumatoid arthritis (RA) who had been treated with tumor necrosis factor-α inhibitors (TNF-αi) which was then discontinued. METHODS: Sixty Korean patients with RA who participated in a 5-year GO-BEFORE and GO-FORWARD extension trials were included in this retrospective study. Golimumab was deliberately discontinued after the extension study (baseline). Patients were then followed by their rheumatologists. We reviewed their medical records for 2 years (max 28 months) following golimumab discontinuation. Patients were divided into a maintained benefit (MB) group and a loss-of-benefit (LB) group based on treatment pattern after golimumab discontinuation. The LB group included patients whose conventional disease-modifying antirheumatic drug(s) were stepped-up or added/switched (SC) and those who restarted biologic therapy (RB). RESULTS: The mean age of patients at baseline was 56.5 years and 55 (91.7%) were females. At the end of follow-up, 23 (38.3%) patients remained in the MB group. In the LB group, 75.7% and 24.3% were assigned into SC and RB subgroups, respectively. Fifty percent of patients lost MB after 23.3 months. Demographics and clinical variables at baseline were comparable between MB and LB groups except for age, C-reactive protein level, and corticosteroid use. Restarting biologic therapy was associated with swollen joint count (adjusted hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.01 to 3.55) and disease duration (adjusted HR, 1.12; 95% CI, 1.02 to 1.23) at baseline. CONCLUSIONS: Treatment strategies after discontinuing TNF-αi are needed to better maintain disease control and quality of life of patients with RA. | |
33811036 | Five-year treat-to-target outcomes after methotrexate induction therapy with or without ot | 2021 Apr 2 | OBJECTIVES: To compare outcomes of different treatment schedules from the care in early rheumatoid arthritis (CareRA) trial over 5 years. METHODS: Patients with RA completing the 2-year CareRA randomised controlled trial were eligible for the 3-year observational CareRA-plus study. 5-year outcomes after randomisation to initial methotrexate (MTX) monotherapy with glucocorticoid bridging (COBRA-Slim) were compared with MTX step-up without glucocorticoids or conventional synthetic disease-modifying antirheumatic drug (DMARD) combinations with glucocorticoid bridging, per prognostic patient group. Disease activity (Disease Activity Score based on 28 joints calculated with C reactive protein (DAS28-CRP)) and functionality (Health Assessment Questionnaire (HAQ)) were compared between treatment arms using longitudinal models; safety and drug use were detailed. RESULTS: Of 322 eligible patients, 252 (78%) entered CareRA-plus, of which 203 (81%) completed the study. Treatments for high-risk patients resulted in comparable DAS28-CRP (p=0.539) and HAQ scores over 5 years (p=0.374). Low-risk patients starting COBRA-Slim had lower DAS28-CRP (p<0.001) and HAQ scores (p=0.041) than those starting only on MTX. At study completion, 114/203 (56%) patients never had their original DMARD therapy intensified, with comparable rates between all treatments. Safety was comparable between treatments in high-risk patients. In low-risk patients, there were 18 adverse events in 10 COBRA-Slim and 36 in 17 patients treated with initial MTX monotherapy (p=0.048). Over 5 years, 22% of patients initiated biologics, 25% took glucocorticoids for >3 months and 17% for >6 months outside the bridging period. CONCLUSIONS: All intensive treatments with glucocorticoids bridging demonstrated excellent 5 year outcomes. Initiating COBRA-Slim was comparably effective as more complex treatments for high-risk patients with early RA and more effective than initial MTX monotherapy for low-risk patients with limited need for biologics and chronic glucocorticoid use. | |
34028703 | Efficacy of Long-Term Treatment with Once-Daily Baricitinib 2 mg in Patients with Active | 2021 Jun | INTRODUCTION: To evaluate long-term efficacy of once-daily baricitinib 2 mg in patients with active rheumatoid arthritis who had an inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or biologic DMARDs (bDMARD). METHODS: Data from patients treated with baricitinib 2 mg daily in two 24-week, phase III studies, RA-BUILD (csDMARD-IR; NCT01721057) and RA-BEACON (bDMARD-IR; NCT01721044), and one long-term extension study (RA-BEYOND; NCT01885078), were analyzed (120 weeks). The main outcomes were achievement of low-disease activity (LDA; Simple Disease Activity Index [SDAI] ≤ 11), clinical remission (SDAI ≤ 3.3), Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5 and improvement from baseline of ≥ 0.22, and safety. Analysis populations included (1) all patients and (2) never-rescued patients. Completer and non-responder imputation (NRI) analyses were conducted on each population. RESULTS: In RA-BUILD, 684 were randomized (229 to baricitinib 2 mg, 180 of whom completed RA-BUILD and entered RA-BEYOND). In RA-BEACON, 527 were randomized (174 to baricitinib 2 mg, 117 of whom completed RA-BEACON and entered RA-BEYOND). In RA-BUILD-BEYOND, 85.1% (63/74, completer) and 27.5% (63/229, NRI) of csDMARD-IR patients treated with baricitinib 2 mg achieved SDAI LDA; 40.5% (30/74, completer) and 13.1% (30/229, NRI) were in SDAI remission; 62.2% (46/74, completer) and 20.1% (46/229, NRI) had HAQ-DI ≤ 0.5 and 81.1% (60/74, completer); and 26.2% (60/229, NRI) achieved ≥ 0.22 change from baseline at week 120. In RA-BEACON-BEYOND, 86.5% (32/37, completer) and 18.4% (32/174, NRI) of bDMARD-IR patients treated with baricitinib 2 mg achieved SDAI LDA; 24.3% (9/37, completer) and 5.2% (9/174, NRI) were in SDAI remission; 50.0% (19/38, completer) and 10.9% (19/174, NRI) had HAQ-DI ≤ 0.5; and 73.7% (28/38, completer) and 16.1% (28/174, NRI) achieved ≥ 0.22 change from baseline at week 120. Rates of adverse events of special interest were consistent with previous reports. CONCLUSIONS: Long-term treatment with baricitinib 2 mg demonstrated efficacy for up to 120 weeks and was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01721057, NCT01721044, and NCT01885078. | |
34913662 | Septic Arthritis: Diagnosis and Treatment. | 2021 Dec 1 | Septic arthritis must be considered and promptly diagnosed in any patient presenting with acute atraumatic joint pain, swelling, and fever. Risk factors for septic arthritis include age older than 80 years, diabetes mellitus, rheumatoid arthritis, recent joint surgery, hip or knee prosthesis, skin infection, and immunosuppressive medication use. A delay in diagnosis and treatment can result in permanent morbidity and mortality. Physical examination findings and serum markers, including erythrocyte sedimentation rate and C-reactive protein, are helpful in the diagnosis but are nonspecific. Synovial fluid studies are required to confirm the diagnosis. History and Gram stain aid in determining initial antibiotic selection. Staphylococcus aureus is the most common pathogen isolated in septic arthritis; however, other bacteria, viruses, fungi, and mycobacterium can cause the disease. After synovial fluid has been obtained, empiric antibiotic therapy should be initiated if there is clinical concern for septic arthritis. Oral antibiotics can be given in most cases because they are not inferior to intravenous therapy. Total duration of therapy ranges from two to six weeks; however, certain infections require longer courses. Consideration for microorganisms such as Neisseria gonorrhoeae, Borrelia burgdorferi, and fungal infections should be based on history findings and laboratory results. | |
32573420 | Interleukin 17E associates with haematologic involvement and autoantibody production in pr | 2021 Mar | OBJECTIVES: Primary Sjögren's syndrome (pSS) is one of the most prevalent systemic autoimmune diseases characterised by inflammation and tissue damage of exocrine glands, especially salivary or lacrimal gland. IL-17 related immune response is pathogenic with proinflammatory feature in pSS. However, whether IL-17E, an IL-17 family member, is involved in pSS pathogenesis or not, has not been determined. METHODS: Serum levels of IL-17E and IL-17A as comparison in 107 patients with pSS and 42 healthy controls were determined with multiplex cytokine assays. EULAR Sjögren's syndrome disease activity index (ESSDAI) score was calculated. Laboratory parameters were measured by standard laboratory techniques. The inflammatory infiltration of minor labial gland biopsies was graded based on numbers of lymphocyte and quantified by Focus Score (FS). Expression of IL-17E and IL-17A in the biopsy was evaluated with immunohistochemistry. RESULTS: Significantly elevated IL-17E in pSS patients associated with ESSDAI, haematologic disorders and autoantibody production, including anti-nuclear antibodies (ANA), rheumatoid factor (RF) and anti-SSA antibodies were found. Histopathological features showed that expression of IL-17E was found in labial salivary gland and correlated with lymphocytic infiltration. CONCLUSIONS: IL-17E expression in pSS patients was increased and associated with haematologic disorders, autoantibody production and lymphocytic infiltration in salivary gland. This finding indicated that IL-17E is involved in pSS pathogenesis. |