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ID PMID Title PublicationDate abstract
32482045 A Case of Rheumatoid Arthritis with Strongyloides stercoralis Hyperinfection. 2020 Jun 2 The patient was a 83-year- old male who worked as a farmer. He had complaints of weight loss, abdominal pain and joint pains for almost 5 months. Twenty days ago, the patient was checked at another hospital for complaints of occasional coughing and bloody sputum. He was treated with a diagnosis of pneumonia. His respiratory complaints were reduced, but there was no relief of his ongoing abdominal pain. Gastroduodenoscopy and colonoscopy were performed to examine for possible etiologies of continuous abdominal pain. Biopsies were taken from duodenal bulbus and second duodenal segment. Intense eosinophilic leukocyte infiltration and Strongyloides stercoralis larvae were observed in pathologic examination. The patient was successfully treated with albendazole 2x400 mg/day for 7+7 day.
32556473 Up to 5-year retention of abatacept in Belgian patients with moderate-to-severe rheumatoid 2020 Sep Favorable efficacy and safety profiles have been demonstrated for abatacept in patients with rheumatoid arthritis (RA) in randomized controlled trials, but these data require validation during long-term follow-ups in routine clinical practice. This study explored long-term safety and retention rates in RA patients treated with intravenous abatacept in the Belgian cohort of the international AbataCepT In rOutiNe clinical practice (ACTION) study (NCT02109666). This non-interventional, observational, longitudinal study included Belgian patients aged ≥ 18 years with moderate-to-severe RA who started intravenous abatacept treatment as first- or second/further-line biologic therapy in routine clinical practice. Between October 2010 and December 2012, 141 patients were enrolled in this cohort, of whom 135 evaluable patients (6 biologic-naïve; 129 previously exposed to ≥ 1 prior biologic disease modifying anti-rheumatic drugs) were eligible for the descriptive analysis; 131/135 were included in the effectiveness analysis. Mean disease duration was 10.5 years (standard deviation 9.7) before abatacept initiation. RA patients presented with high disease activity and comorbidity rate, having failed multiple previous treatment options. In this cohort, the 5-year abatacept retention rate was 34% (95% confidence interval, 23-45%) per protocol, and 51% (95% confidence interval, 40-61%) when temporary discontinuations of abatacept > 84 days (n = 24) were not considered as treatment discontinuations. After 5 years of abatacept treatment, clinical outcomes were favorable [good/moderate European League Against Rheumatism (EULAR) responses in 91.7% patients]. No new safety signals were detected for abatacept in routine clinical practice. In this difficult-to-treat Belgian RA population, high retention rates, good clinical outcomes and favorable safety profile were observed with abatacept.
31958281 Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by 2020 Jan OBJECTIVE: To evaluate the relationship between disease activity and radiographic progression in rheumatoid arthritis, three phase III studies of SB4, SB2 and SB5 (biosimilars of etanercept, infliximab and adalimumab) were pooled to assess radiographic progression by disease activity status. METHODS: Patients from each study with radiographic data were pooled and grouped based on disease activity state (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)), determined by disease activity score based on 28-joint count (DAS28) per erythrocyte sedimentation rate, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) at different time points. Mean change in modified Total Sharp Score (mTSS) and the proportion of radiographic non-progressors of higher disease activity groups (LDA, MDA and HDA) in reference to remission were summarised descriptively, with comparison of ORs using logistic models. RESULTS: 1265 patients were included. In all treatments combined, the 1 year mean change in mTSS was 0.03, 0.4, 0.3 and 1.3 and proportion of radiographic non-progressors was 79.8%, 78.1%, 74.1% and 58.4% in the week 24/30 DAS28-determined remission, LDA, MDA and HDA groups, respectively. ORs (95% CIs) of the proportion of non-progressors were lowest in the HDA group in reference to remission (0.35 (0.23 to 0.54)), followed by MDA (0.72 (0.50 to 1.05)) and LDA (0.90 (0.55 to 1.48)) groups. Similar trends were observed when disease activity was assessed using SDAI or CDAI. CONCLUSION: A pooled analysis of radiographic assessment data from three biosimilar studies showed that radiographic progression is small overall but increases with worse disease activity. TRIAL REGISTRATION NUMBERS: NCT01895309, NCT01936181 and NCT02167139.
33213130 COVID-19 pandemic and biological therapy in rheumatologic disorders: how to deal with? 2020 Nov 19 The outbreak of coronavirus disease 2019 (COVID-19) has involved more than 159 countries and more than 5 million people worldwide. A 40-year-old man with a history of rheumatoid arthritis treated with prednisolone, Disease-Modifying Anti-Rheumatic Drugs (DMARDs), and biologic agents was admitted with chief complaints of fever, chills, malaise, myalgia, and dyspnea. Chest computed tomography showed bilateral subsegmental atelectasis and diffuse ground-glass opacities in both lungs inducing the suspicion of COVID-19 infection. The oro-nasopharynx swab sample for COVID-19 polymerase chain reaction was positive. In addition to supportive care, lopinavir/ritonavir 400/100 mg twice daily and oseltamivir (75 mg) twice daily were started in combination with a starting dose of hydroxychloroquine (400 mg). The methotrexate dose was decreased, and the dose of prednisolone was increased to 30 mg for 10 days. Azathioprine and adalimumab were continued at previous doses. The use of biologic agents and DMARDs in rheumatic patients is a serious challenge in the COVID-19 pandemic. In conclusion, during the COVID-19 pandemic, due to the key roles of cytokines in the promotion of the disease, the rheumatic patients may benefit from continuing their previous treatment, which may have protective effects.
31820713 Expression of Galectin-9 and correlation with disease activity and vascular endothelial gr 2020 Jul OBJECTIVES: Despite the important role of Galectin-9 (Gal-9) in inflammation and angiogenesis, only a few studies on Galectin-9 expression have been performed in rheumatoid arthritis (RA) patients. The present study aimed to identify the concentration of Galectin-9 in plasma, its expression in peripheral blood T cell subsets in RA patients, and the association between Galectin-9 and vascular endothelial growth factor (VEGF) in RA. METHODS: One hundred and five active RA patients and 52 age- and sex-matched healthy controls (HCs) were enrolled in the study. Gal-9, vascular endothelial growth factor (VEGF), and tumour necrosis factor (TNF)-α level in plasma were determined by ELISA. The intracellular positive expression rates and medium fluorescence intensity (MFI) of Gal-9 and VEGF in T cell subsets, were examined by flow cytometry. RESULTS: Plasma Gal-9, TNF-α, and VEGF levels were higher in the RA group than in the HCs group. The plasma Gal-9 level positively correlated with Gal-9 expression in the total lymphocyte and CD3+ T cell, CRP, SDAI, and CDAI of RA patients. The Gal-9 expressions in the cytoplasm of CD4+ T, CD8+ T, Treg, and DNT cells positively correlated with plasma TNF-α levels in RA patients. The Gal-9 expressions in CD4+ T and CD8+ T subsets also positively correlated with plasma VEGF levels. The plasma VEGF levels and VEGF expressions in CD4+ T, CD8+ T, and Treg subsets positively correlated with SDAI and CRP in RA patients. CONCLUSIONS: Gal-9 can be a potential biomarker for RA disease activity. Gal-9 is probably associated with angiogenesis processing in RA.
31880308 Abatacept in rheumatoid arthritis and the risk of cancer: a world observational post-marke 2020 Sep 1 OBJECTIVES: We aimed to investigate whether abatacept used in patients for RA was associated with an increased risk of reporting overall cancer and specific cancers, including breast, lung, lymphoma, melanoma and non-melanoma skin cancer when compared with other biologic DMARDs (bDMARDs). METHODS: We performed an observational study within VigiBase, the World Health Organization's global database of individual case safety reports, from 2007 to 2017 to compare the cases of cancer reported in RA patients exposed to abatacept with those reported in RA patients exposed to other bDMARDs. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% CIs of the exposure odds among spontaneous reporting of cancers to the exposure odds among other reported adverse effects. RESULTS: We identified 15 846 adverse effects reported in RA patients who received abatacept and 290 568 adverse effects reported in RA patients treated with other bDMARDs. Compared with other bDMARDs, the use of abatacept was not associated with an increased risk of reporting cancer overall [ROR 0.98 (95% CI 0.91, 1.05)]. Analyses by specific cancer sites showed a significantly increased ROR for melanoma [1.58 (95% CI 1.17, 2.08)], but not for other specific cancer sites. CONCLUSION: Compared with other bDMARDs, exposure to abatacept in RA patients was only significantly associated with an increased risk of reporting melanoma. This increased risk is consistent with the properties of abatacept (CTLA-4 agonist) since it has an opposite action than ipilimumab, an antibody that blocks CTLA-4 and is approved for the treatment of malignant melanoma. TRIAL REGISTRATION: ClinicalTrials.gov (http://clinicaltrials.gov), NCT03980639.
31043548 Placebo Response in Rheumatoid Arthritis Clinical Trials. 2020 Jan OBJECTIVE: Understanding the placebo response is critical to interpreting treatment efficacy, particularly for agents with a ceiling to their therapeutic effect, where an increasing placebo response makes it harder to detect potential benefit. The objective of this study is to assess the change in placebo responses over time in rheumatoid arthritis (RA) randomized placebo-controlled trials (RCT) for drug licensing authorization. METHODS: The Cochrane Controlled Trials Register database was searched to identify RCT of biological or targeted synthetic disease-modifying antirheumatic drugs (DMARD) in RA. Studies were excluded if patients were conventional synthetic DMARD (csDMARD)-naive, not receiving background csDMARD therapy, or were biologic experienced. Metaregression model was used to evaluate changes in American College of Rheumatology (ACR) 20, ACR50, and ACR70 treatment response over time. RESULTS: There were 32 trials in total: anti-tumor necrosis factor therapy (n = 15), tocilizumab (n = 4), abatacept (n = 2), rituximab (n = 2), and Janus kinase inhibitors (n = 9). From 1999 to 2018, there was no significant trend in the age or sex of patients in the placebo arm. Disease duration, swollen joint count, and 28-joint count Disease Activity Score using erythrocyte sedimentation rate at baseline all significantly declined over time. There was a statistically significant increase in placebo ACR50 and ACR70 responses (ACR50 β = 0.41, 95% CI 0.09-0.74, p = 0.01; ACR70 β = 0.18, 95% CI 0.04-0.31, p = 0.01) that remained significant after controlling for potential confounders. CONCLUSION: There has been a rise in the placebo response in RA clinical trials over the last 2 decades. Shifting RA phenotype, changes in trial design, and expectation bias are possible explanations for this phenomenon. This observation has important implications when evaluating newer novel agents against established therapies.
31129759 Spa therapy and rehabilitation of musculoskeletal pathologies: a proposal for best practic 2020 Jun Spa therapy is a heterogeneous collection of treatments and methods based on natural resources. It is often considered as an option in the common therapeutic approach to many musculoskeletal disorders, as well as respiratory, vascular, and dermatological disorders. The objective of this paper is to highlight possible interactions between rehabilitation and spa medicine in the field of musculoskeletal disorders, through an analysis of the scientific literature, in order to give the practitioner the ability to integrate good clinical practice in the field of rehabilitation through practical application involving spa therapies. The literature search was conducted using Medline, PEDro, Cochrane Database, and Google Scholar. Only studies published in English and works concerning the implementation of spa thermal treatment in neuro-musculoskeletal diseases were included. Specifically, the publications analyzed dealt with the treatment of diseases such as arthritis, rheumatic arthritis, ankylosing spondylitis, and low back pain through the use of thermal spa therapies. In conjunction with its widespread use in clinical practice, many studies in the literature suggest the effectiveness of crenobalneotherapy for a number of musculoskeletal disorders, generally those which are chronic and debilitating, finding significant clinical improvement both in terms of pain and functional limitations. Some of the guidelines formulated by national and international bodies on the treatment of specific diseases, such as the Italian Rheumatology Society (SIR) and the Osteoarthritis Research Society International (OARSI) guidelines, recognize the value of thermal medicine as a complement, but not a replacement, for conventional therapy (pharmacological or not).
32900936 Gold-based therapy: From past to present. 2020 Sep 15 Despite an abundant literature on gold nanoparticles use for biomedicine, only a few of the gold-based nanodevices are currently tested in clinical trials, and none of them are approved by health agencies. Conversely, ionic gold has been used for decades to treat human rheumatoid arthritis and benefits from 70-y hindsight on medical use. With a view to open up new perspectives in gold nanoparticles research and medical use, we revisit here the literature on therapeutic gold salts. We first summarize the literature on gold salt pharmacokinetics, therapeutic effects, adverse reactions, and the present repurposing of these ancient drugs. Owing to these readings, we evidence the existence of a common metabolism of gold nanoparticles and gold ions and propose to use gold salts as a "shortcut" to assess the long-term effects of gold nanoparticles, such as their fate and toxicity, which remain challenging questions nowadays. Moreover, one of gold salts side effects (i.e., a blue discoloration of the skin exposed to light) leads us to propose a strategy to biosynthesize large gold nanoparticles from gold salts using light irradiation. These hypotheses, which will be further investigated in the near future, open up new avenues in the field of ionic gold and gold nanoparticles-based therapies.
33463122 Distinctive Expression of Bone Metabolism-related Genes between PBMCs from Condylar Hyperp 2020 Oct 18 Bone morphogenetic proteins (BMPs) and wingless (Wnt) signaling molecules and their antagonists, such as sclerostin and noggin, have been identified to have different effects on bone metabolism. This research intended to evaluate the transcript levels of CTNNB1 (catenin beta 1protein), SOST (sclerostin protein), BMP4 (Bone Morphogenetic Protein 4 protein), and NOG (noggin protein) bone metabolism-related genes in peripheral blood mononuclear cells (PBMCs) from condylar hyperplasia (CH) patients in comparison to rheumatoid arthritis (RA), ankylosing spondylitis (AS), and healthy individuals. PBMCs were separated from blood samples of 10 patients with CH, AS, RA, and 10 healthy controls. SYBR Green real-time polymerase chain reaction (PCR) was used for quantitative analysis of CTNNB1, SOST, BMP4, and NOG messenger RNAs (mRNAs). The expression of CTNNB1 was significantly upregulated in CH and AS patients compared with healthy individuals and RA patients. The difference of SOST expression was not significant between all groups. The BMP4 expression was significantly downregulated in AS, CH, and RA patients compared with healthy controls. The NOG expression was downregulated in RA, AS, and CH groups, however, it was only significant in CH and RA patients compared with controls.CH and AS patients were distinguished from RA by the upregulatedCTNNB1 expression. These results demonstrated that CTNNB1, BMP4, and NOG, but not SOST, may contribute to the pathogenesis of CH, AS, and RA.
31973752 Investigation of toll-like receptor (TLR) 4 inhibitor TAK-242 as a new potential anti-rheu 2020 Jan 23 BACKGROUND: Proper blocking of toll-like receptor (TLR) activation during disease progression has been reported to have inhibitory effect on the pathogenesis of rheumatoid arthritis (RA). We tested whether the TLR4 inhibitor TAK-242 had potential as a remedy for rheumatoid arthritis. METHODS: The therapeutic effect of TAK-242 was tested in vitro using the human rheumatoid fibroblast-like synoviocyte (FLS) line MH7A or primary human FLS and in an adjuvant-induced arthritis (AIA) rat model. RESULTS: TAK-242 dose dependently inhibited the increased expression of IL-6, IL-8, MMP-1, and VEGF in LPS-stimulated MH7A cells. It also inhibited the expression of IL-6 and IL-8 in poly(I:C), TLR3 activator-stimulated primary FLS, but not in IL-1β-stimulated primary FLS. These findings suggest that TAK-242 blocks a specific signaling pathway to some degree. Further, TAK-242 slightly inhibited mobilization of NF-κB into nuclei. In the AIA rat model, TAK-242 significantly reversed the body weight and paw thickness of AIA rats to the normal state at a dose of 5 mg/kg, but not at 3 mg/kg, and reduced the increased serum level of IL-6 and VEGF in AIA rats. It also significantly ameliorated inflammatory symptoms of joint tissues at day 21 of treatment, according to histology and RT-PCR. CONCLUSIONS: Based on the drug repositioning concept, TAK-242, which is used for the treatment of TLR4-mediated inflammatory diseases, shows potential for cost-effective development as a remedy for rheumatoid arthritis or to control the progression of RA.
32666748 Drug-neutralizing Antibodies against TNF-α blockers as Biomarkers of Therapy Effect Eval 2020 Jun 30 INTRODUCTION: TNF-α blocker therapy is part of the treatment with biologics used in the management of inflammatory joint diseases. In recent years, drug-induced neutralizing antibodies have been shown to have a negative effect on the course of the disease process. AIM: To investigate drug-induced neutralizing antibodies against TNF-α blocking drugs used in patients with inflammatory joint diseases and their effect on the clinical course of the disease. MATERIALS AND METHODS: The study included 121 (56.8%) patients with rheumatoid arthritis, 50 (23.5%) patients with ankylosing spondylitis, 42 (19.7%) patients with psoriatic arthritis, and 31 sex and age-matched healthy controls. The patients were monitored at 0, 6, 12, and 24 months after initiation of TNF-α blocker treatment. The demographic data, vital signs and the parameters of inflammatory activity (C-reactive protein, erythrocyte sedimentation rate, and disease activity indices) were analyzed in all patients. Drug-induced anti-TNF-α blockers antibodies (adalimumab and etanercept) were analyzed using ELISA. Statistical analysis was performed with SPSS v. 24. RESULTS: Drug-induced neutralizing antibodies against adalimumab were obtained in 11.57% of patients at 6 month, in 17.64% at 12 month, and in 24.8% at 24 month. Drug-induced neutralizing antibodies to etanercept were not demonstrated in patients followed up at 6 months, at 7.77% at 12 months, and at 9.63% at 24 months. Between the presence of neutralizing antibodies to blockers of TNF-α and indices available for disease activity, there is a strong positive correlation and Pearson Correlation = 0.701, p=0.001. Patients with poor clinical response and available antibodies against adalimumab at 12 months were 82.36% and patients treated with etanercept 71.42%. The difference between the two groups was non-significant (U = 0.527, p> 0.05). Patients with poor clinical response and available anti-adalimumab antibodies at 24 month were 75%, and in patients treated with etanercept - 87.50%, the difference between the two groups not being able to reach significance (U = 0.623, p> 0.05). CONCLUSION: Drug-induced neutralizing antibodies against TNF-α blockers (adalimumab and etanercept) have a negative effect on the course of inflammatory joint disease and can be used as reliable biomarker to assess the effect of the treatment with these drugs.
32706178 Paediatric infections in the first 3 years of life after maternal anti-TNF treatment durin 2020 Sep BACKGROUND: Most anti-tumour necrosis factor (anti-TNF) agents are transferred across the placenta and may increase paediatric susceptibility to infections. AIMS: To assess the risk of paediatric infections after maternal anti-TNF treatment. METHODS: Population-based cohort study in Denmark, Finland and Sweden 2006-2013 in which 1027 children born to women with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis or inflammatory bowel disease, treated with anti-TNF, and 9346 children to women with non-biologic systemic treatment, were compared to 1 617 886 children of the general population. Children were followed for 3 years. RESULTS: Adjusted by maternal age, parity, smoking, body mass index, country and calendar year, the incidence rate ratios with 95% confidence interval (CI) for hospital admissions for infection in the first year were 1.43 (1.23-1.67) for anti-TNF and 1.14 (1.07-1.21) for non-biologic systemic treatment, and 1.29 (1.11-1.50) and 1.09 (1.02-1.15), respectively, when additionally adjusting for adverse birth outcomes. There was a slight increase in antibiotic prescriptions in the second year for anti-TNF, 1.19 (1.11-1.29), and for non-biologic systemic treatment, 1.10 (1.07-1.13). There was no difference among anti-TNF agents, treatment in the third trimester, or between mono/combination therapy with non-biologic systemic treatment. CONCLUSIONS: Both anti-TNF and non-biologic systemic treatment were associated with an increased risk of paediatric infections. However, reassuringly, the increased risks were present regardless of treatment in the third trimester, or with combination treatment, and were not persistent during the first 3 years of life. Our findings may indicate a true risk, but could also be due to unadjusted confounding by disease severity and healthcare-seeking behaviour. This may in turn shift the risk-benefit equation towards continuation of treatment even in the third trimester.
31379121 Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis 2020 Jan OBJECTIVE: Rheumatoid arthritis (RA) patients with concomitant fibromyalgia (FM) exhibit alterations in brain connectivity synonymous with central sensitization. This study was undertaken to investigate how peripheral inflammation, the principal nociceptive stimulus in RA, interacts with brain connectivity in RA patients with FM. METHODS: RA patients with concomitant FM and those without FM (FM+ and FM-, respectively; n = 27 per group) underwent functional connectivity magnetic resonance imaging. Seed-to-whole-brain functional connectivity analyses were conducted using seeds from the left mid/posterior insula and left inferior parietal lobule (IPL), which are regions that have been previously linked to FM symptoms and inflammation, respectively. The association between functional connectivity and erythrocyte sedimentation rate (ESR) was assessed in each group separately, followed by post hoc analyses to test for interaction effects. Cluster-level, family-wise error (FWE) rates were considered significant if the P value was less than 0.05. RESULTS: The group of RA patients with FM and those without FM did not differ by age, sex, or ESR (P > 0.2). In FM+ RA patients, increased functional connectivity of the insula-left IPL, left IPL-dorsal anterior cingulate, and left IPL-medial prefrontal cortex regions correlated with higher levels of ESR (all FWE-corrected P < 0.05). Post hoc interaction analyses largely confirmed the relationship between ESR and connectivity changes as FM scores increased. CONCLUSION: We report the first neurobiologic evidence that FM in RA may be linked to peripheral inflammation via pronociceptive patterns of brain connectivity. In patients with such "bottom-up" pain centralization, concomitant symptoms may partially respond to antiinflammatory treatments.
32451909 Population Pharmacokinetic-Pharmacodynamic Relationships of Sarilumab Using Disease Activi 2020 Nov BACKGROUND: Sarilumab is a human monoclonal antibody blocking the interleukin-6 receptor alpha (IL-6Rɑ) approved for the treatment of moderately to severely active rheumatoid arthritis in adults with inadequate response or intolerance to other disease-modifying antirheumatic drugs. OBJECTIVE: The aim of the current analysis was to describe sarilumab exposure-response relationships. METHODS: Population pharmacokinetic/pharmacodynamic (PopPK/PD) models were developed describing the time course of the 28-joint disease activity score by C-reactive protein (DAS28-CRP) and absolute neutrophil count (ANC) using data from phase I-III studies (NCT01011959, NCT01061736, NCT01709578, NCT01768572) after subcutaneous sarilumab 50-150 mg every week or 100-200 mg every 2 weeks. RESULTS: The time course of DAS28-CRP and ANC after sarilumab administration was described by semi-mechanistic, indirect-response models. Drug effect was predicted to be numerically greater at median exposure for the 200 mg every 2 weeks regimen versus the 150 mg every 2 weeks regimen, for both DAS28-CRP (50% vs. 47%) and ANC reduction from baseline (39% vs. 31%), with the latter showing less fluctuations within a dosing interval. Four covariates were retained in the final models: body weight, baseline rheumatoid factor status, anti-cyclic citrullinated peptide status, and concomitant methotrexate. There was no clinically meaningful influence of investigated covariates for either model. CONCLUSION: The PopPK/PD models showed numerically greater reductions in DAS28-CRP and ANC with sarilumab 200 mg every 2 weeks than with 150 mg every 2 weeks. There was no clinically meaningful influence of investigated covariates. These data contribute to the totality of evidence that supports a sarilumab subcutaneous starting dose of 200 mg every 2 weeks, with a subsequent reduction to 150 mg every 2 weeks in the event of laboratory abnormalities such as neutropenia.
33082707 Disease-Specific Autoantibodies Induce Trained Immunity in RA Synovial Tissues and Its Gen 2020 Much evidence suggests that trained immunity is inappropriately activated in the synovial tissue in rheumatoid arthritis (RA), but the underlying mechanism remains unclear. Here, we describe how RA-specific autoantibody deposits can train human monocytes to exert the hyperactive inflammatory response, particularly via the exacerbated release of tumor necrosis factor α (TNFα). Comparative transcriptomic analysis by plate-bound human IgG (cIgG) or β-glucan indicated that metabolic shift towards glycolysis is a crucial mechanism for trained immunity. Moreover, the cIgG-trained gene signatures were enriched in synovial tissues from patients with ACPA- (anticitrullinated protein antibody-) positive arthralgia and undifferentiated arthritis, and early RA and established RA bore a great resemblance to the myeloid pathotype, suggesting a historical priming event in vivo. Additionally, the expression of the cIgG-trained signatures is higher in the female, older, and ACPA-positive populations, with a predictive role in the clinical response to infliximab. We conclude that RA-specific autoantibodies can train monocytes in the inflamed lesion as early as the asymptomatic stage, which may not merely improve understanding of disease progression but may also suggest therapeutic and/or preventive strategies for autoimmune diseases.
33078547 Involvements of long noncoding RNAs in obesity-associated inflammatory diseases. 2021 Apr Obesity is associated with chronic low-grade inflammation that affects the phenotype of multiple tissues and therefore is implicated in the development and progression of several age-related chronic inflammatory disorders. Importantly, a new family of noncoding RNAs, termed long noncoding RNAs (lncRNAs), have been identified as key regulators of inflammatory signalling pathways that can mediate both pretranscriptional and posttranscriptional gene regulation. Furthermore, several lncRNAs have been identified, which are differentially expressed in multiple tissue types in individuals who are obese or in preclinical models of obesity. In this review, we examine the evidence for the role of several of the most well-studied lncRNAs in the regulation of inflammatory pathways associated with obesity. We highlight the evidence for their differential expression in the obese state and in age-related conditions including insulin resistance, type 2 diabetes (T2D), sarcopenia, osteoarthritis and rheumatoid arthritis, where obesity plays a significant role. Determining the expression and functional role of lncRNAs in mediating obesity-associated chronic inflammation will advance our understanding of the epigenetic regulatory pathways that underlie age-related inflammatory diseases and may also ultimately identify new targets for therapeutic intervention.
32822775 Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may exp 2020 Nov We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis (RA). Eighty RA patients were randomized to tocilizumab (n = 40) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids (GC) (n = 40) for 3 months. Forty healthy subjects with similar age and sex served as controls. We measured: (a)perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b)pulse wave velocity (PWV), (c)global LV longitudinal strain (GLS), (d)global work index (GWI) using speckle tracking echocardiography and e)C-reactive protein (CRP), malondialdehyde (MDA) and protein carbonyls (PCs) as oxidative stress markers at baseline and post-treatment. Compared to controls, RA patients had impaired glycocalyx and myocardial deformation markers (P < 0.05). Compared with baseline, tocilizumab reduced PBR(2.14 ± 0.2 versus 1.97 ± 0.2 μm; P < 0.05) while no significant differences were observed post-csDMARDs + GC(P > 0.05). Compared with csDMARDs + GC, tocilizumab achieved a greater increase of GLS, GWI and reduction of MDA, PCs and CRP(P < 0.05). The percent improvement of glycocalyx thickness (PBR) was associated with the percent decrease of PWV, MDA, PCs and the percent improvement of GLS and GWI(P < 0.05). Tocilizumab improves endothelial function leading to a greater increase of effective myocardial work than csDMARDs + GC through a profound reduction of inflammatory burden and oxidative stress. This mechanism may explain the effects of tocilizumab on COVID-19. CLINICAL TRIAL REGISTRATION: url: https://www.clinicaltrials.gov. Unique identifier: NCT03288584.
32189149 Retention rates and identification of factors associated with anti-TNFα, anti-IL17, and a 2020 Sep INTRODUCTION: Biologic disease-modifying antirheumatic drugs (bDMARDs) play a pivotal role in the treatment of psoriatic arthritis (PsA). Despite this, their discontinuation due to inefficacy or adverse events is often observed. The aims of this study are to describe retention rates and treatment trends of anti-TNFα, anti-IL17, and anti-IL12/23R agents in patients with PsA and to identify factors associated with bDMARDs discontinuation in a real-world clinical setting. METHODS: A retrospective cohort study based on the analysis of the three Italian prescription cohorts of patients with PsA has been performed. Survival analysis was performed using Kaplan-Meier curves and Cox proportional-hazards model. RESULTS: During the follow up, which lasted 25.5 (12-60) months, 68 patients discontinued a bDMARD: 13 for primary failure, 12 for secondary failure, 15 for adverse events, 5 for remission, 12 because of lost at follow-up, and 11 for other causes. Cox proportional-hazards demonstrated that a shorter disease duration (HR 0.994991, 95% CI 0.9910336-0.9989647, p = 0.014) and first-line bDMARD (HR 0.5090986, 95% CI 0.3073519-0.8432722, p = 0.009) have a protective role on bDMARD retention rate, while the multivariable analysis failed in demonstrating an independent protective role of male sex on drug retention rate (p = 0.083). No significant differences in retention rate have been found regarding biologic drugs, combination therapy or monotherapy, and class of bDMARD (anti-TNFα or anti-pIL12/23R and anti-IL-17). CONCLUSIONS: This study shows that a shorter disease duration and treatment with a first-line bDMARD are predictors of bDMARDs retention rate, further highlighting the importance of early diagnosis of PsA. Key Points • No significant difference in retention among patients treated with anti-IL17A, anti-IL12/23R, and anti-TNFα agents has been demonstrated. • A shorter disease duration and first-line bDMARD treatment are associated with persistence in biologic treatment.
33142189 Increased monocyte chemoattractant protein-1 and nitrotyrosine are associated with increas 2020 Dec OBJECTIVES: Etanercept, a tumor necrosis factor inhibitor, is an effective drug for patients with active rheumatoid arthritis (RA). Monocyte chemoattractant protein-1 (MCP-1) and nitrotyrosine (NT) are pro-inflammatory biomolecules associated with satiety and increased body weight. We evaluated whether MCP-1 and NT are associated with decreased inflammation or increased body mass during etanercept therapy in active RA patients. METHODS: RA patients with moderate to high disease activity were enrolled to receive add-on etanercept (25 mg subcutaneous injection, biweekly) for at least one year, combined with sustained treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). RESULTS: Forty patients received add-on etanercept and 15 received DMARDs alone. At the end of one year, etanercept significantly reduced the disease activity score of 28 joints, C-reactive protein, and erythrocyte sedimentation rate. Moreover, etanercept significantly increased the body weight, body mass index (BMI), as well as MCP-1 and NT levels, compared to that in the csDMARD-only group. CONCLUSIONS: Increased serum MCP-1 and NT levels in RA patients with moderate to high disease activity, who underwent one-year etanercept treatment, might be attributed to increase in body weight and BMI rather than induction of more severe autoimmune inflammation.