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ID PMID Title PublicationDate abstract
31743270 Paraneoplastic Arthritides: Insights to Pathogenesis, Diagnostic Approach, and Treatment. 2021 Dec 1 Paraneoplastic arthritides are a group of inflammatory rheumatic syndromes induced by an occult and manifest malignancy, characterized by a wide range of musculoskeletal signs and symptoms that masquerade other rheumatic diseases such as rheumatoid arthritis. Although the pathogenesis of paraneoplastic arthritides is unknown, immune-mediated mechanisms can induce a paraneoplastic syndrome, with a dominant feature the polyarthritis. Common entities of paraneoplastic arthritides include paraneoplastic polyarthritis, hypertrophic osteoarthropathy, remitting seronegative symmetrical synovitis with pitting edema, palmar fasciitis and polyarthritis, and polyarthritis and panniculitis associated with pancreatic carcinoma. The electronic databases PubMed and Scopus were scrutinized using the following terms: paraneoplastic arthritis, paraneoplastic polyarthritis, or paraneoplastic rheumatic diseases. Abstracts, full articles, and selected references were reviewed. The aim of the present narrative review article was to describe the clinical characteristics, diagnostic evaluation, and management of paraneoplastic arthritides, and highlight the challenges that health care providers may encounter, distinguishing those conditions from other autoimmune rheumatic disorders. Future studies are needed to give insight into the mechanisms associated with paraneoplastic arthritides, leading to the development of novel diagnostic biomarkers.
34916702 [Multicentric reticulohistiocytosis: A case report]. 2021 Dec 18 A 65-year-old woman developed erythema, papules and nodules over the body. Some nodules of her auricles and hands like string beads. Besides, she suffered from symmetrical swelling and pain of multiple joints, morning stiffness with deformity of joints; She had elevated erythrocyte sedimentation rate and C reactive protein levels; Her rheumatoid factor and antinuclear antibody were positive; Joints destruction was found with X-ray imaging; Skin pathology showed Dermal infiltrate of abundant histiocytes, part of them with a ground-glass appearance; A CD68 immunohistochemical stain was positive and the cells were negative for S100, CD1a. These findings were diagnostic evidences of multicentric reticulohistiocytosis (MRH). The patient received high-dose of glucocorticoids combinated with immunosuppressive agents, and achieved a satisfactory effect. MRH was a rare multisystem disease characterized by papulonodular mucocutaneous and destructive arthritis, and its pathogeny was not yet completely understood. The typical lesions of MRH were hard papules or nodules that usually occured on the hands, face and arms. Classic coral bead appearance from periungual cutaneous nodules that were characteristic of MRH. MRH was an inflammatory joint disease, affecting almost all the appendicular joints and characterized by joint multiple, symmetrical, destructive, progressive disability. Joints destruction of the distal interphalangeal joints was a unique feature of MRH. In addition to skin and joints, it could also involve other systems. There were no diagnostic laboratory markers for MRH. Laboratory examinations had often been found to be non-specific. Imageological examination mainly showed bone and joint destruction. Skin biopsy was the best test to diagnose MRH, the typical histopathological findings included an infiltrate with histiocytes and multinucleated giant cells with a ground-glass appearing in eosinophilic cytoplasm, and the immunohistochemical stain was positive for CD68. The diagnosis was typically made based on the clinical presentation, supportive radiographic findings and skin biopsy. MRH was easily possible to mistake for other more common autoimmune conditions, such as rheumatoid arthritis, psoriatic arthritis, osteoarthritis, and dermatomyositis, but the distinctive clinical, radiographic, and histologic features could aid in differentiating these diseases. MRH could mimic other rheumatic diseases, besides, it could also coexist with cancer or other autoimmune disorders. There was no standardized treatment for MRH. However, Nonsteroidal anti-inflammatory drugs, glucocorticoid, Immunosuppressant, biologic medications, and bisphosphonates had been used with varying degrees of curative effect. Treatment with glucocorticoid combined with immunosuppressants were effective for rash and arthritis, early use of them should be strongly considered, and refractory cases could be treated with biological agents. By reporting a MRH case and reviewing literature, this paper aims to help the clinicians improve the understanding of this rare disease, and suggests that when one diagnosis cannot explain the whole picture of the disease, and further evidence should be sought to confirm the diagnosis.
33592889 Evaluation of contrast-enhanced ultrasound for activity of rheumatoid arthritis: A protoco 2021 Feb 5 BACKGROUND: Contrast-enhanced ultrasound (CEUS) refers to a technique that uses contrast medium to strengthen the echo of backscatter, which can significantly improve the resolution, sensitivity and specificity of ultrasound diagnosis. As a quantitative imaging examination of blood flow signals, CEUS has allowed detection of synovial microvascularization in the joints of patients with rheumatoid arthritis (RA). However, the results of these studies have been contradictory. Therefore, the purpose of this study is to evaluate the value of CEUS in the activity of RA disease. METHODS: We will search PubMed, Embase, Cochrane Library, and CNKI from their inception to the December 20, 2020, without restrictions of language and publication status. Two investigators will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. This study will only include high quality clinical cohort or case control studies. Statistical analysis was performed by using the Review Manager version 5.3 and the STATA version 14.0 (Stata Corp, College Station, TX, USA) softwares. RESULTS: This systematic review will determine the value of CEUS in RA activity scores. CONCLUSION: The results of this study will provide a useful basis for high-quality CEUS to evaluate RA activity score. SYSTEMATIC REVIEW REGISTRATION: INPLASY2020120125.
33320245 Ten-year analysis of the risk of severe outcomes related to low-dose glucocorticoids in ea 2021 Aug 2 OBJECTIVES: To explore the 10-year tolerability profile of glucocorticoids (GC) use in patients with early RA. METHODS: Analysis of 10-year outcome from the early arthritis ESPOIR cohort. Patients were stratified in two groups, without or with GC treatment at least once during their follow-up. The primary outcome was a composite of deaths, cardiovascular diseases (CVD), severe infections and fractures. The weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method. RESULTS: Among the 608 patients [480 women, mean age of 47.5  (12.1) years], 397 (65%) received low-dose GC [median 1.9 mg/day (IQR 0.6-4.2), mean cumulative prednisone dose 8468 mg (8376), mean duration 44.6 months (40.1)]. In univariate analysis, over 95 total events (10 deaths, 18 CVDs, 32 fractures and 35 severe infections), patients taking GC experienced more events (n = 71) than those without GC (n = 24) (P =0.035). Highest cumulative exposure of GC (≥8.4 g) was associated with highest risk of occurrence of the primary outcome (24.3%, P =0.007), CVDs (7.9%, P =0.001) and severe infections (9.9%, P =0.024). The risk of events over time was significantly associated with GC, age, hypertension and ESR. The risk associated with GC treatment increased between the first follow-up visit [hazard ratio (HR) at 1 year = 0.46, 95% CI: 0.23, 0.90] and 10 years (HR = 6.83, 95% CI: 2.29, 20.35). CONCLUSION: The 10-year analysis of this prospective early RA cohort supports a dose and time-dependent impact of low-dose GC treatment, with a long-term high risk of severe outcomes. TRIAL REGISTRATION: (ClinicalTrials.gov Identifier: NCT03666091).
34331578 Cardiorespiratory fitness and physical activity in people who have rheumatoid arthritis at 2021 Dec Lower cardiorespiratory fitness (CRF) and physical activity (PA) associate with higher cardiovascular disease (CVD) risk, but the relationship between CRF and PA in people who have rheumatoid arthritis (RA) at an increased CVD risk (CVD-RA) is not known. The objectives of this study were to determine the levels of CRF and PA in people who have CVD-RA and to investigate the association of CRF with PA in people who have CVD-RA. A total of 24 consecutive patients (19 women) with CVD-RA (> 4% for 10-year risk of fatal CVD development as calculated using the Systematic Coronary Risk Evaluation)-were included in the study. CRF was assessed with a graded maximal exercise test determining maximal oxygen uptake (VO(2max)). PA was assessed with an accelerometer to determine the amount of step count, sedentary, light and moderate-to-vigorous physical activity (MVPA) minutes per day. Mean age of patients was 65.3 ± 8.3 years. CRF mean values were 16.3 ± 1.2 ml·kg(-1) min(-1), mean step count per day was 6033 ± 2256, and the mean MVPA time was 16.7 min per day. Significant positive associations were found for CRF with step count (B = 0.001, P = 0.01) and MVPA time (B = 0.15, P = 0.02); a negative association was found for CRF with sedentary time (B =  - 0.02, P = 0.03). CRF is low and is associated with step count, sedentary time and MVPA time in people who have RA at an increased CVD risk.
34526398 Annexin A1 attenuates cardiac diastolic dysfunction in mice with inflammatory arthritis. 2021 Sep 21 Rheumatoid arthritis (RA) carries a twofold increased incidence of heart failure with preserved ejection fraction, accompanied by diastolic dysfunction, which can lead to death. The causes of diastolic dysfunction are unknown, and there are currently no well-characterized animal models for studying these mechanisms. Current medications for RA do not have marked beneficial cardio-protective effects. K/BxN F1 progeny and KRN control mice were analyzed over time for arthritis development, monitoring left ventricular diastolic and systolic function using echocardiography. Excised hearts were analyzed by flow cytometry, qPCR, and histology. In pharmacological experiments, K/BxN F1 mice were treated with human recombinant AnxA1 (hrAnxA1, 1 μg/mouse) or vehicle daily. K/BxN F1 mice exhibited fully developed arthritis with normal cardiac function at 4 wk; however, by week 8, all mice displayed left ventricular diastolic dysfunction with preserved ejection fraction. This dysfunction was associated with cardiac hypertrophy, myocardial inflammation and fibrosis, and inflammatory markers. Daily treatment of K/BxN F1 mice with hrAnxA1 from weeks 4 to 8 halted progression of the diastolic dysfunction. The treatment reduced cardiac transcripts of proinflammatory cytokines and profibrotic markers. At the cellular level, hrAnxA1 decreased activated T cells and increased MHC II(low) macrophage infiltration in K/BxN F1 hearts. Similar effects were obtained when hrAnxA1 was administered from week 8 to week 15. We describe an animal model of inflammatory arthritis that recapitulates the cardiomyopathy of RA. Treatment with hrAnxA1 after disease onset corrected the diastolic dysfunction through modulation of both fibroblast and inflammatory cell phenotype within the heart.
33156359 Temporal artery biopsy for suspected giant cell arteritis: a retrospective analysis. 2021 Oct Temporal artery biopsy (TAB) is one of the diagnostic criteria of giant cell arteritis (GCA) according to 1990 ACR criteria and remains a tool for diagnosis. Although clinicians perform TAB with an intent to confirm suspected GCA, some biopsies result in negative and some lead to non-GCA diagnoses. We aim to review the diagnoses after TAB biopsy performed for suspected GCA and also wanted to evaluate the diagnostic changes and concomitant diseases that develop over time. The patients who had undergone TAB for suspected GCA were identified using the record entry code for TAB. Patients meeting the classification criteria for GCA were designated as the GCA group and not meeting criteria were designated as a non-GCA group. Other classification criteria were implemented for the non-GCA group diseases. A total of 51 patients (Female: 62.7%, median age: 72.1 ± 7.4 years) who had undergone TAB for suspected GCA were evaluated. TAB was positive in 23 (69.6%) of the 33 patients who met the GCA classification criteria. No significant difference was found between TAB-positive and TAB-negative GCA patients in terms of clinical and laboratory parameters. In the non-GCA group, 12 patients had isolated polymyalgia rheumatica (PMR), and the diagnoses of the remaining six patients were as follows: four large vessel vasculitis (LVV) not satisfying GCA diagnostic criteria, one chronic myelomonocytic leukemia (CMML), and one amyloidosis. TAB was negative in all patients with isolated PMR. TAB showed primary amyloidosis in one patient. Out of 33 GCA patients, 21 had "isolated" GCA, four had GCA + Rheumatoid arthritis (RA), seven had GCA + PMR, and one had GCA + polymyositis. RA was diagnosed antecedent to GCA in two patients, and after GCA in the other two patients. One of the patients had developed GCA 20 years after polymyositis had been diagnosed. TAB was found to be positive in two-thirds of patients with suspected GCA. Late-onset RA and rarely other inflammatory rheumatic diseases may develop in the course of GCA.
34628400 SUPPORTIVE PHARMACOTHERAPY FOR SYSTEMIC AUTOIMMUNE DISEASES WITH HYPERIMMUNOCOMPLEX SYNDRO 2021 Sep Purpose of the study was to determine the pharmacotherapy of systemic autoimmune diseases with hyperimmunocomplex syndrome based on ABC/VEN analysis of drugs according to the ATC code C05SH. Among the systemic autoimmune diseases are systemic lupus erythematosus, systemic vasculitis, psoriasis, rheumatoid arthritis. Pharmacoeconomic methods of analysis, in particular ABC/VEN analysis, are used to select effective and safe drugs Important tasks of pharmacotherapy of systemic autoimmune diseases include the study of immune-dependent complexes on the background of hyperimmunocomplex syndrome. Circulating immune complexes are eliminated by phagocytosis through the spleen, lungs, kidneys and liver. Therefore, the main task of pharmacotherapy of systemic autoimmune diseases with hyperimmunocomplex syndrome is to control the functions of these organs and systems. Marketing research of drugs by INN Quercetin of the ATC-code C05CX by assortment, countries-manufacturers, dosage forms, registration certificates was carried out. Pharmacoeconomic studies have been conducted. According to the results of ABC analysis, drugs by INN Quercetin of the ATC-code C05CX were distributed in descending order of value. It is proved that group A (the most expensive in price) included 77.4% of drugs from the total number of doctor's appointments. According to the results of VEN-analysis by INN Quercetin of the ATC-code C05CX, it is calculated that all drugs are recommended to be included as non-essential. Drugs for group N occupy the highest financial costs prescribed by doctors for pharmacotherapy (100%). The niche of the A/N matrix has the highest indicator for doctors' appointments and financial expenses (77.4%). The results of the study provide an opportunity to make administrative and managerial decisions in determining the pharmacotherapy of systemic autoimmune diseases with hyperimmunocomplex syndrome to improve the use of drugs in hospitals.
34423698 LncRNA ZNF667-AS1 alleviates rheumatoid arthritis by sponging miR-523-3p and inactivating 2021 Nov BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease, which compromises the synovial membrane resulting in chronic inflammation. Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) are implicated in the pathogenesis of RA. This study investigated the role of lncRNA ZNF667-AS1 in RA progression. METHODS: Synovial tissues and fibroblast-like synoviocytes (FLSs) were obtained from patients with RA. Gene expression was measured using RT-qPCR. Chondrocytes were treated with lipopolysaccharide (LPS) to establish in vitro models of OA. Cell counting kit-8 (CCK-8), western blot, and enzyme-linked immunosorbent assay (ELISA) were used to examine the proliferation and inflammatory cytokine production in chondrocytes. Animal models of OA were established in SD rats. Peripheral blood mononuclear cells (PBMCs) were isolated from the OA rats. Flow cytometry was used to measure the changes of the inflammatory T-helper cell 17 (Th17) cells. The relationship between ZNF667-AS1 and miR-523-3p was verified by luciferase reporter assay. RESULTS: ZNF667-AS1 was downregulated in RA-FLSs and LPS-stimulated chondrocytes. ZNF667-AS1 overexpression significantly promoted cell proliferation and inhibited the production of IL-6, IL-17 and TNF-α in LPS-stimulated chondrocytes. Additionally, ZNF667-AS1 overexpression reduced the generation of CD4 + IL-17+ cells. In mechanism, ZNF667-AS1 acted a sponge for miR-523-3p. MiR-523-3p overexpression reversed the ZNF667-AS1-mediated regulation of cell proliferation and inflammation. Furthermore, miR-523-3p overexpression abolished the inhibitory effects of ZNF667-AS1 on the JAK/STAT signalling activation. CONCLUSION: ZNF667-AS1 exerts protective effects during RA development by sponging miR-523-3p and inactivating the JAK/STAT signalling.
33734147 Well-being and Perceived Stigma in Individuals With Rheumatoid Arthritis and Fibromyalgia: 2021 May 1 INTRODUCTION: The presence or absence of clearly defined symptoms and underlying pathophysiology may be a crucial variable related to variability in well-being and stigmatization in individuals with chronic pain (ICPs). In the context of pain, absence of clearly defined symptoms and pathophysiology deviates from the widely endorsed biomedical model and as such, may lead to stigmatization, which in turn could be related to ICPs' well-being. OBJECTIVES: The present study compared physical, psychological, social well-being, and perceived stigmatization in individuals with clearly defined symptoms and underlying pathophysiology (rheumatoid arthritis, RA) and individuals with less well understood symptoms and pathophysiology (fibromyalgia, FM) using daily diaries. Furthermore, the association between daily perceived stigmatization and daily well-being was examined. MATERIALS AND METHODS: Seventy-nine participants with FM, 86 participants with RA, and 33 participants with both diagnoses completed a diary for 14 consecutive days. RESULTS: Compared to individuals with RA, individuals with FM and individuals with both diagnoses reported worse daily well-being. After controlling for age, pain duration, and daily pain, differences between FM and RA remained significant for social well-being and completion of plans. Differences between RA and the dual diagnosis group remained significant for completion of plans, negative affect, and isolation. Furthermore, results suggested more stigmatization in individuals with FM than in individuals with RA. Individuals with both diagnoses reported equal stigmatization as individuals with FM, but more stigmatization than individuals with RA. Finally, increased levels of perceived stigma were associated with lower well-being. DISCUSSION: Findings highlight that the absence of clearly defined symptoms and pathophysiology could be contributing to greater feelings of stigmatization, which may be detrimental for ICPs' well-being.
34779576 Upadacitinib in patients from China, Brazil, and South Korea with rheumatoid arthritis and 2021 Dec AIM: This study assessed the efficacy and safety of upadacitinib (UPA), in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in Chinese, Brazilian, and South Korean patients with active rheumatoid arthritis (RA) and an inadequate response (IR) to csDMARDs. METHODS: Patients on stable csDMARDs were randomized (1:1) to once-daily UPA 15 mg or matching placebo (PBO) for a 12-week, double-blind period. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 12. RESULTS: In total, 338 patients were randomized and treated, of whom 310 (91.7%) completed the double-blind phase. The study met the primary endpoint of ACR20 at week 12 for UPA 15 mg vs PBO (71.6% vs 31.4%, P < .001), with a treatment difference observed as early as week 1. All ranked and other key secondary endpoints, including more stringent responses such as ACR50, ACR70 (≥50%/70% improvement in ACR criteria), and Disease Activity Score in 28 joints using C-reactive protein <2.6, were met for UPA 15 mg vs PBO. The incidence of serious infections (2.4% vs 0.6%) and herpes zoster (HZ: 1.8% vs 0.6%) was higher with UPA 15 mg vs PBO. There was one case of venous thromboembolism reported in the UPA group. CONCLUSION: UPA 15 mg in combination with csDMARDs demonstrated clinical and functional improvement and an acceptable safety profile over 12 weeks among patients from China, Brazil, and South Korea who had moderately to severely active RA and an IR to csDMARDs.
29975258 ASYMMETRIC HYDROXYCHLOROQUINE MACULAR TOXICITY WITH APHAKIC FELLOW EYE. 2021 Mar 1 BACKGROUND/PURPOSE: Retinal toxicity associated with antimalarial drug use in inflammatory conditions is well described and may be more common than previously recognized. Antimalarial drugs bind to melanin in ocular tissues, particularly the retinal pigment epithelium, but the mechanism of toxicity and its relation to light is unclear. METHODS: Case report. RESULTS: A 62-year-old white woman with erosive rheumatoid arthritis developed hydroxychloroquine toxicity in her phakic eye, with her aphakic fellow eye only mildly affected. CONCLUSION: We report the clinical evaluation of this rare case of asymmetrical hydroxychloroquine retinopathy and present a hypothesis regarding the mechanism of drug toxicity.
34002351 Inflammatory arthritis-associated pyoderma gangrenosum: a systematic review. 2021 Oct INTRODUCTION/OBJECTIVES: Pyoderma gangrenosum (PG) is a rare, rapidly progressive neutrophilic dermatosis commonly associated with systemic inflammatory diseases. We aimed to characterize the association of PG and inflammatory arthritis, as little is known outside of case reports and small cohort studies. METHOD: We performed a systematic review in PubMed, EMBASE, and Scopus from inception to present using the terms arthritis and pyoderma gangrenosum. Patient demographics, clinical presentation, and treatment outcomes were recorded. Descriptive statistics and stratified analysis were used to compare factors of interest by type of arthritis. RESULTS: A total of 1399 articles were screened, and 129 patients with inflammatory arthritis and PG were included in the review. The most common types of arthritis were rheumatoid arthritis (RA) (50.4%), inflammatory bowel disease (IBD)-associated arthritis (10.9%), and psoriatic arthritis (8.5%). In the vast majority of cases, joint symptoms preceded PG, by a median of 10 years (inter-quartile range [IQR] 5-16). Corticosteroid monotherapy and biologic therapies, used alone or in combination, resulted in improvement or complete resolution of ulcers 71.4% and 67.3% of the time, respectively. Within the latter, infliximab, adalimumab, and anakinra were most successful in inducing remission overall. RA and non-RA did not differ significantly in treatment success or healing time. CONCLUSIONS: This study shows that PG is frequently preceded by inflammatory arthritis, most commonly RA. Clinicians used a wide variety of treatment regimens with variable outcomes. While larger studies are needed to standardize the treatment of inflammatory arthritis-associated PG, this study suggests that in addition to systemic corticosteroids, biologic medications can be effective treatment options for these patients. KEY POINTS: • Inflammatory arthritis, most commonly rheumatoid arthritis, often precedes rather than follows pyoderma gangrenosum. • Other forms of arthritis associated with PG included IBD-associated arthritis and psoriatic arthritis. • Biologic therapies, such as infliximab, adalimumab, and anakinra, were largely successful in treating arthritis-associated pyoderma gangrenosum and may play an important role in corticosteroid-sparing therapy or in a maintenance regimen for this subset of patients. • The type of inflammatory arthritis associated with pyoderma gangrenosum may not be a helpful treatment guide as it was not significantly associated with treatment outcomes or healing time.
33886522 Total Shoulder Arthroplasty Is Cost-Effective Compared with Hemiarthroplasty: A Real-World 2021 Aug 18 BACKGROUND: Although outcome studies generally demonstrate the superiority of a total shoulder arthroplasty (TSA) over a hemiarthroplasty (HA), comparative cost-effectiveness has not been well studied. From a publicly funded health-care system's perspective, this study compared the costs and quality-adjusted life-years (QALYs) in patients who underwent TSA with those in patients who underwent HA. METHODS: We conducted a cost-utility analysis using a Markov model to simulate the costs and QALYs for patients undergoing either TSA or HA over a lifetime horizon to account for costs and medically important events over the patient lifetime. Subgroup analyses by age groups (≤50 or >50 years) were performed. A series of sensitivity analyses were performed to assess robustness of study findings. The results were presented in 2019 U.S. dollars. RESULTS: TSA was dominant as it was less costly ($115,785 compared with $118,501) and more effective (10.21 compared with 8.47 QALYs) than HA over a lifetime horizon. Changes to health utility values after TSA and HA had the largest impact on the cost-effectiveness findings. At a willingness-to-pay (WTP) threshold of $50,000 per QALY gained, HA was not found to be cost-effective. The probability that TSA was cost-effective was 100%. CONCLUSIONS: Based on a WTP of $50,000 per QALY gained, from the perspective of Canada's publicly funded health-care system, TSA was found to be cost-effective in all patients, including those ≤50 years of age, compared with HA. LEVEL OF EVIDENCE: Economic and Decision Analysis Level II. See Instructions for Authors for a complete description of levels of evidence.
33427621 Antibody to peptidoglycan recognition protein (PGLYRP)-2 as a novel biomarker in rheumatoi 2021 Sep OBJECTIVES: To identify novel autoantigens from circulating immune complexes (CICs) in rheumatoid arthritis (RA) patients and further explore their clinical significance. METHODS: From serum samples of 10 early RA (ERA) patients and 10 healthy donors, CICs were isolated and subjected to orbitrap mass spectrometry for autoantigen identification. Antibodies against the peptidoglycan recognition protein-2 (PGLYRP-2) derived from CICs were further detected by indirect enzyme-linked immunosorbent assay (ELISA) in 178 patients with RA, compared with 59 osteoarthritis (OA), 59 systemic lupus erythematosus (SLE), 55 ankylosing spondylitis (AS), 95 primary Sjögren's syndrome (pSS) and 50 healthy controls (HC). RESULTS: Thirty-three potential antigens out of 323 proteins were identified from CICs of RA patients. The autoantibodies to PGLYRP-2 were significantly increased in RA patients with 42.70% sensitivity and 85.20% specificity in comparison to other rheumatic diseases and healthy controls. The prevalence of anti-PGLYRP-2 was also elevated in subgroups of RA, with 34.72% in ERA, 35.29% in RF negative and 42.86% in anti-CCP negative patients. Further analysis suggested that anti-PGLYRP-2 was potentially accompanied with production of other autoantibodies in RA. In addition, we found by homology analysis that an epitope of PGLYRP-2442-447 mimics amino acid residues 431-436 of N-acetylmuramoyl-L-alanine amidase (NAMLAA) in actinomyces naeslundii. CONCLUSIONS: Autoantibody against PGLYRP-2 was identified as a promising biomarker in RA, especially in early and seronegative patients.
34585777 TNF-Polarized Macrophages Produce Insulin-like 6 Peptide to Stimulate Bone Formation in Rh 2021 Dec The risk of osteoporosis is increased in rheumatoid arthritis (RA). Anti-tumor necrosis factor (TNF) therapy has markedly improved the outcomes of RA patients but does not improve osteoporosis in some reports. This could be a combined result of disease severity and other therapeutic agents, such as glucocorticoids that accelerate osteoporosis progression. We evaluated the effects of anti-TNF therapy on osteoporosis in an animal model of RA and explored the possible mechanisms involved. Six-week-old TNF transgenic (TNF-Tg) mice with early stage erosive arthritis were treated with TNF antibody (Ab) or control immunoglobulin (IgG) weekly for 4 weeks. We found that TNF Ab completely blocked the development of erosive arthritis in TNF-Tg mice, but only slightly increased vertebral bone mass, associated with reduction in parameters of both bone resorption and formation. Similarly, TNF Ab slightly increased trabecular bone mass in tibias of 8-month-old TNF-Tg mice with advanced erosive arthritis. Interestingly, TNFα increased osteoblast differentiation from mouse bone marrow stromal cells (BMSCs) containing large number of macrophages but not from pure mesenchymal progenitor cells (MPCs). TNFα-polarized macrophages (TPMs) did not express iNos and Arginase 1, typical markers of inflammatory and resident macrophages. Interestingly, TPMs stimulated osteoblast differentiation, unlike resident and inflammatory macrophages polarized by IL-4 and interferon-λ, respectively. RNA-seq analysis indicated that TPMs produced several anabolic factors, including Jagged1 and insulin like 6 (INSL6). Importantly, inhibition of either Jagged1 or INSL6 blocked TNFα-induced osteoblast differentiation. Furthermore, INSL6 Ab significantly decreased the expansion of TNF-induced MPCs in BMSCs, and anti-TNF Ab reduced INSL6 expression by macrophages in vitro and in TNF-Tg mice in vivo. We conclude that TPMs produce INSL6 to stimulate bone formation and anti-TNF Ab blocks not only enhanced bone resorption but also the anabolic effect of TPMs on bone, limiting its effect to increase bone mass in this model of RA. © 2021 American Society for Bone and Mineral Research (ASBMR).
34380725 Efficacy of therapeutic fasting and plant-based diet in patients with rheumatoid arthritis 2021 Aug 11 BACKGROUND: Previous studies have shown beneficial effects of therapeutic fasting and plant-based dietary interventions on disease activity in patients with rheumatoid arthritis (RA) for a duration of up to 1 year. To date, the effects of such interventions on the gut microbiome and on modern diagnostic markers in patients with RA have not been studied. This trial aims to investigate the clinical effects of therapeutic fasting and a plant-based diet in patients with RA, additionally considering current immunological diagnostic tools and microbiome analyses. METHODS/DESIGN: This trial is an open-label, single-centre, randomised, controlled, parallel-group clinical trial. We will randomly assign 84 patients with RA under a stable standard therapy to either (1) therapeutic fasting followed by a plant-based dietary intervention or (2) to a conventional nutritional counselling focusing on an anti-inflammatory dietary pattern according to the recommendations of the Deutsche Gesellschaft für Ernährung (German society for nutrition). Primary outcome parameter is the group difference from baseline to 12 weeks on the Health Assessment Questionnaire (HAQ). Other secondary outcomes include established clinical criteria for disease activity and treatment response in RA (Disease Activity Score 28, Simple Disease Activity Index, ACR-Response Criteria), changes in self-reported health and physical functional ability, mood, stress, quality of life, dietary behaviour via 3-day food records and a modified Food Frequency Questionnaire, body composition, changes in the gut microbiome, metabolomics and cytometric parameters. Outcomes will be assessed at baseline and day 7, after 6 weeks, 12 weeks and after 6 months. ETHICS AND DISSEMINATION: Ethical approval to process and analyse data, and to publish the results was obtained through the institutional review board of Charité-Universitätsmedizin Berlin. Results of this trial will be disseminated through peer-reviewed publications and scientific presentations. TRIAL REGISTRATION NUMBER: NCT03856190.
33086882 Cost-utility analysis of the anti-TNF therapy for rheumatoid arthritis in a real-world bas 2021 Oct BACKGROUND: Spending on drugs provided by the Brazilian Public Health System (BPHS) for the treatment of rheumatoid arthritis (RA) increased substantially with the beginning of the supply of biological disease-modifying anti-rheumatic drugs (bDMARD). This study aims to perform a cost-utility analysis of the most used biological drugs for the treatment of RA in Brazil. METHODS: a Markov model was used to carry out the cost-utility analysis. The data were obtained from a prospective cohort of RA patients using adalimumab, etanercept, and golimumab in Brazil. The BPHS perspective was adopted and the time horizon was five years. Deterministic and probabilistic sensitivity analyses were performed to evaluate the uncertainty. RESULTS: golimumab was the most cost-effective drug. Etanercept was dominated by golimumab. Adalimumab presented an incremental cost-utility ratio (ICUR) of $95,095.37 compared to golimumab in five years of follow-up. These results were confirmed by sensitivity analyses. CONCLUSION: the utility among adalimumab, etanercept, and golimumab was similar and the cost was the component that most impacted the economic model. Therefore, depending on the agreed price with the drug manufacturers, the incremental cost-utility ratio may vary among them.
34224890 Long-Term Results of Anterior-Only Lumbar Interbody Fusions in Rheumatoid Arthritis Patien 2021 Oct OBJECTIVE: Rheumatoid arthritis (RA) is a risk factor of lumbar spine surgical failure. The interest of anterior lumbar fusion in this context remains unknown. This retrospective study aimed to compare the outcome of anterior-only fusions between RA patients and non-RA (NRA) patients to treat lumbar spine degenerative disorders. METHODS: NRA and RA groups including anterior-only fusion were compared. Clinical data (Visual Analog Scale score axial back pain scale, the Oswestry Disability Index, and a questionnaire of satisfaction regarding the surgical result); radiologic data (bone fusion, sagittal balance analysis); and adverse events were assessed using repeated measure 1-way analysis of variance. RESULTS: The mean follow-up was 9.5 years (95% confidence interval [7.1-12.2]) for the RA group (n = 13) and 9.4 years (95% confidence interval [8.7-10.3]) for the NRA group (n = 36). Anterior fusion improved clinical outcome without any effect of RA (Visual Analog Scale score axial back pain scale; P < 0.001/Oswestry Disability Index; P = 0.01). The presence of RA influenced neither the satisfaction as the regards the surgical result nor spine balance nor bone fusion. Context of RA increased the surgical revision rate (10 patients [76.9%] for RA group vs. 3 patients [8.8%] for the NRA group; P = 0.001) because of the occurrence of an adjacent segment disease needing surgical revision (P = 0.028), especially the occurrence of intervertebral frontal dislocation (P = 0.02). CONCLUSIONS: As noticed for posterior-only fusion, the anterior lumbar approach in RA patients does not seem to avoid the occurrence of an adjacent segment disease.
33663487 The efficacy, safety and cost-effectiveness of hydroxychloroquine, sulfasalazine, methotre 2021 Mar 4 BACKGROUND: Tumor necrosis factor α inhibitors (TNFi) is effective for rheumatoid arthritis (RA) patients who fail to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Because of high cost, the discontinuation is common but often lead to disease relapse. The study aims to investigate, if the combination therapy of csDMARDs is more effective in reducing disease relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi and MTX. METHODS: It will be a two-stage trial. In the first stage, all RA patients who failed to csDMARDs treatment [disease activity score 28 (DAS28)-CRP > 3.2] will receive MTX plus TNFi for no more than 12 weeks. Patients achieving DAS28-CRP < 3.2 during the first stage will be randomized into three groups at 1:1:1 ratio: (A) add hydroxychloroquine (HCQ) and sulfasalazine (SSZ) for the first 12 weeks and then remove TNFi but continue other treatments for the next 48 weeks; (B) maintain TNFi + MTX for 60 weeks; and (C) maintain TNFi + MTX for the first 12 weeks and then remove TNFi but continue MTX monotherapy for the next 48 weeks. The primary outcome will be disease relapse (DAS28-CRP increases by at least 0.6 and > 3.2). Secondary outcomes will include the incremental cost per reducing 1 case of relapse; patient reported intolerance to the treatment; adverse events; change of mean disease activity measured by DAS28, clinical disease activity index (CDAI) and simplified disease activity index (SDAI); the proportion of modified Sharp score increase < 0.3; ultrasound-detected remission in hands; Health Assessment Questionnaire Disability Index (HAQ-DI) and health related quality of life [the five-level EuroQol-5D (EQ-5D-5L) and short form-6D (SF-6D)]. DISCUSSION: The aim of this trail will be to seek effective treatment options of preventing relapse of RA. The results of the current study may provide an instructive recommendation for more economical application of TNFi treatment in RA. Trial registration NCT, NCT02320630. Registered on 16 December 2014. https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=3&cx=-jg9qo2 .