Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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32864695 | Predicting treatment response to IL6R blockers in rheumatoid arthritis. | 2020 Dec 1 | Patients with severe, active RA who have not responded to conventional therapy may receive biological disease modifying anti-rheumatic drugs (bDMARDs). However, 40% of cases do not achieve complete disease control, resulting in a negative impact on patient quality of life and representing a waste of healthcare resources. Ongoing research seeks to establish biomarkers, which can be used to predict treatment response to biologics in RA to enable more targeted approaches to treatment. However, much of the work has focused on one class of biologic drug, the TNF inhibitors (TNFi). Here, we will review the current state of research to identify biomarkers predictive of response to the class of bDMARDs targeting the IL6R. While success has been limited thus far, serum drug and low ICAM1 levels have shown promise, with associations reported in independent studies. The challenges faced by researchers and lessons learned from studies of TNFi will be discussed. | |
33300420 | Feasibility and estimated efficacy of blood flow restricted training in female patients wi | 2021 May | Objectives: The study aimed to evaluate the feasibility of a blood flow restriction (BFR) training regimen in patients with rheumatoid arthritis (RA); and to compare the effects of 4 weeks of BFR training with low-intensity strength training on muscle strength, muscle endurance, and joint pain in patients with RA.Method: In this non-blinded pilot randomized controlled trial, 18 women with RA aged 18-65 years performed low-intensity strength training for the lower limbs three times a week for 4 weeks, and were randomized to train with or without occlusion bands. The primary outcomes were registration of the recruitment process, compliance with training sessions, side effects, perceived pain, and a satisfaction survey. The secondary outcomes were changes in muscle strength, muscle endurance, and joint pain.Results: The findings of this pilot study included a challenging recruitment process, well tolerated training and test protocols, overall good patient satisfaction, no serious side effects, and high compliance. Both groups achieved significant improvements in knee extensor strength from baseline to follow-up, with a change of 11.5 kg [interquartile range (IQR) 9.8;13.0] in the intervention group and 8.4 kg (IQR 5.5;12.4) in the control group, and a significant between-group difference in favour of the intervention group (p = 0.0342).Conclusions: The feasibility results of this study indicated a challenging recruitment process, general satisfaction with the BFR and exercises, good compliance, and only expected non-serious side effects. BFR training may improve knee extensor strength in women with RA, compared low-intensity strength training without BFR. | |
32375173 | The Patient Experienced Symptom State (PESS): a patient-reported global outcome measure th | 2020 Nov 1 | OBJECTIVES: In RA, Patient Acceptable Symptom State assesses disease from the patient's perspective, which does not correspond either to disease remission or to full control of disease impact. This study aims to explore the properties of a novel multilevel Patient Experienced Symptom State (PESS). METHODS: This was a cross-sectional analysis of two datasets of patients with RA. PESS was assessed through the question: 'Consider how your RA has affected you. If you remain in the coming months as you have been the last week, how would you rate your condition?', with five levels (from 'very bad' to 'very good'). Construct validity of PESS was assessed against validated disease activity [DAS28, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI)] and impact measures [RA Impact of Disease (RAID) and modified HAQ]. Multiple pairwise comparisons between groups and receiver-operating characteristic curves with Youden Index were performed. RESULTS: A total of 1407 patients [74% female, mean (S.d.) age 53.5 (13.4) years, mean disease duration 14.3 (12.0) years and mean DAS28 3.0 (1.5)] were analysed. Overall, 16.3% considered themselves as being in 'very good', 21.6% in 'good' and 31.9% in 'acceptable' state. Disease activity and impact measures differed significantly across the five levels (P < 0.01). Cut-off values corresponding to 'good' and 'very good' PESS states were in the range of low disease activity/remission (for 'good' and 'very good': DAS28-ESR-4v ≤2.6/≤2.3; CDAI ≤5.0/≤3.1; SDAI ≤5.1/≤3.8, respectively) and very low disease impact (RAID domains all ≤1). CONCLUSION: PESS 'very good' status corresponds to currently recommended targets for RA management and reflects full control of disease impact. PESS appears to be an easy-to-use and relevant measure in the evaluation of patients with RA. | |
31951186 | Diagnostic Role of Survivin in Rheumatoid Arthritis: A Systematic Review. | 2020 | Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which is characterized by the hyperplasia of synovial tissue. Survivin is a member of the inhibitor of apoptosis protein family, which facilitates the formation of functional T-cell receptor and differentiation of memory T cells. Survivin plays an important role in the expression of major histocompatibility complex molecules and mature dendritic cells, which play the main role in the etiology of RA. This systematic review was conducted to investigate the evidence on the role of survivin as a diagnostic and predictive value in RA patients. All published articles related to the subject of interest and published up to 30 March 2018 were searched in three databases, including Google Scholar, PubMed, and Web of Science. After a detailed evaluation of the full-text version of the papers, 23 articles were entered into the study. The elevation of survivin in the preclinical phase of RA and its association with anti-cyclic citrullinated peptide (CCP) antibodies suggested it as a predictor of RA. Recently, survivin has been introduced as the biomarker of joint damage and poor response to antirheumatic treatment in RA patients. Based on the evidence, survivin level had high specificity and sensitivity in the diagnosis of RA patients. The results of the reviewed studies demonstrated that a positive survivin level was associated with the presence of anti-CCP antibodies. | |
32366281 | The impact of sex and gender on immunotherapy outcomes. | 2020 May 4 | Immunotherapies are often used for the treatment, remission, and possible cure of autoimmune diseases, infectious diseases, and cancers. Empirical evidence illustrates that females and males differ in outcomes following the use of biologics for the treatment of autoimmune diseases, e.g., rheumatoid arthritis (RA), infectious diseases, e.g., influenza, and solid tumor cancers. Females tend to experience more adverse reactions than males following the use of a class of biologics referred to as immunotherapies. For immunotherapies aimed at stimulating an immune response, e.g., influenza vaccines, females develop greater responses and may experience greater efficacy than males. In contrast, for immunotherapies that repress an immune response, e.g., tumor necrosis factor (TNF) inhibitors for RA or checkpoint inhibitors for melanoma, the efficacy is reportedly greater for males than females. Despite these differences, discrepancies in reporting differences between females and males exist, with females have been historically excluded from biomedical and clinical studies. There is a critical need for research that addresses the biological (i.e., sex) as well as sociocultural (i.e., gender) causes of male-female disparities in immunotherapy responses, toxicities, and outcomes. One-size-fits-all approaches to immunotherapies will not work, and sex/gender may contribute to variable treatment success, including adherence, in clinical settings. | |
33253580 | Novel DEK-Targeting Aptamer Delivered by a Hydrogel Microneedle Attenuates Collagen-Induce | 2021 Jan 4 | DEK protein is critical to the formation of neutrophil extracellular traps (NETs) in rheumatoid arthritis (RA). Blocking DEK using the aptamer DTA via articular injection has been shown to have robust anti-inflammatory efficacy in a previous study. However, DTA is prone to nuclease degradation and renal clearance in vivo. RA is a systemic disease that involves multiple joints, and local injection is impractical in clinical settings. In this study, DTA was modified with methoxy groups on all deoxyribose sugar units and inverted deoxythymidine on the 3' end (DTA4) to enhance its stability against nuclease. DTA4 is stable for 72 h in 90% mouse serum and maintains a high binding affinity to DEK. DTA4 effectively inhibits the formation of NETs and the migration of HUVECs in vitro. DTA4 was then modified with cholesterol on its 5' end to form DTA6. DTA6 dramatically reduces DEK expression in inflammatory RAW264.7 cells. A hydrogel microneedle (hMN) was then fabricated for the transdermal delivery of DTA6. The hMN maintains morphological integrity after absorbing the aptamer solution, effectively pierces the skin, and rapidly releases DTA6 into the dermis. The DTA6-loaded hMN significantly attenuates inflammation and protects joints from cartilage/bone erosion in collagen-induced arthritis (CIA) mice. | |
31762208 | A wide-targeted urinary and serum metabolomics strategy reveals the effective substance of | 2020 Feb | As an important Chinese medicine decoction, Wu-tou decoction has been used to treat rheumatic arthritis for more than a thousand years. We previously reported that the Wu-tou decoction could change the urinary and serum metabolites in adjuvant-induced arthritis rats significantly. The purpose of this research was to confirm the potential biomarkers obtained by previous non-targeted metabolomics study through quantitative analysis by liqui chromatography with tandem mass spectrometry, in the meantime, to further study the effective material basis of Wu-tou decoction. Firstly, the important compounds in the tryptophan metabolism pathway, the arginine and proline metabolism pathway, the amino acid metabolism pathway, the tricarboxylic acid cycle, the vitamin B(6) metabolism pathway, and the phenylalanine metabolism pathway, which were identified as potential biomarkers in previous study, were selected for quantitative analysis. Then the linearity, limit of detection, limit of quantification, selectivity, accuracy, precision, stability, recovery, and matrix effect of the quantitative method were examined. Finally, ten and eighteen metabolites were quantitatively analyzed in the serum and urine, respectively. The results showed that seven out of ten serum potential biomarkers and ten out of eighteen urine potential biomarkers were confirmed as real biomarkers. This research provides a powerful reference for the study on effective material basis of Wu-tou decoction. | |
33180398 | Comparison of Serum Levels of 14-3-3 ETA Proteins between Rheumatoid Arthritis, Osteoarthr | 2020 Jan | 14-3-3 ETA protein, a joint-derived biomarker that up-regulates inflammatory cytokines which enhances local and systemic inflammation and may lead to destructive changes in joints, is thought to be a good diagnostic marker for early RA. To assess the usefulness of serum levels of 14-3-3 ETA in the diagnosis of RA. This is a case-control study which involved 3 groups: group 1 included 30 RA patients, group 2 included 30 primary osteoarthritis patients and group 3 included 30 healthy controls. All study subjects were assessed using laboratory investigations as CBC, ESR, CRP, RF, ACPA as well as serum levels of 14-3-3 ETA protein which were measured through ELISA technique. Mean ± SD levels of 14-3-3 ETA were significantly higher among RA compared to OA and control groups (0.7(0.5), 0.2 (0.1) and 0.3(0.1) ng/ml, respectively) with a sensitivity of 79.3%, specificity of 81.7%, positive predicted value of 86% and negative predicted value of 81%. 14-3-3 ETA also had high diagnostic OR (1478.04). A statistically significant correlation (r= 0.259) was found between serum levels of 14-3-3 ETA and ESR. In conclusion, 14-3-3 ETA is a novel marker for RA that should be used in conjunction with RF and ACPA for diagnosis of the disease. | |
32301430 | Comparative efficacy and safety of current therapies for early rheumatoid arthritis: a sys | 2020 Sep | OBJECTIVES: This systematic literature review (SLR) and network meta-analysis (NMA) was aimed at comparing the relative efficacy and safety of abatacept (ABA) with other currently recommended therapies for patients with early RA. METHODS: An SLR (January 1998 to June 2018) was conducted including MEDLINE®, Embase, and CENTRAL databases, and grey literature. Population was adults with active RA for ≤2 years treated with biologic DMARDs as monotherapy or in combination with conventional DMARDs. A Bayesian NMA was performed using randomised controlled trials (RCTs) and comparisons for ACR50, DAS28 remission, withdrawal due to adverse events and total withdrawal where reported. RESULTS: Ninety publications pertaining to 69 studies (43 RCTs and 26 observational studies) were identified. Twenty-eight RCTs were eligible to be included in the NMA. ABA as monotherapy was similar to the combination of ABA+methotrexate (MTX) for ACR50 (RR: 0.82 [95% CI 0.51-1.35]), and DAS28 remission (RR: 0.69 [95% CI 0.37-1.3]), as well as for withdrawal due to AEs (RR: 2.35 [95% CI 0.69-7.38]) and all-cause withdrawal (RR: 1.73 [95% CI 0.905-3.35]). ABA as monotherapy and ABA+MTX were both comparable to all other therapies for the main efficacy and safety outcomes. Observational study data reported was congruous with the RCT analysis. CONCLUSIONS: The results of this NMA show similar efficacy and safety between ABA (as monotherapy or in combination with MTX) and other biologics in early RA. Further comparison of different treatment options for early RA is warranted as growing research provides evidence for the application of new novel therapies for RA. | |
32436170 | Rheumatoid Nodule Simulating a Parotid Tumor. | 2021 Mar | Rheumatoid nodules are an extra-articular manifestation of rheumatoid arthritis that are rarely found in the maxillofacial region. A 59-year-old woman with rheumatoid arthritis treated with methotrexate, leflunomide, and tocilizumab, presented with an enlarging mass in the left parotid region. Magnetic resonance imaging (MRI) displayed a lesion compatible with a neoplasm. However, an incisional biopsy showed features consistent with a rheumatoid nodule. The patient was managed conservatively, including cessation of methotrexate and initiation of treatment with hydroxychloroquine. At 15-month follow-up, the lesion had a significant reduction in size. To our knowledge, this is the first case report of a rheumatoid nodule in the parotid region. Although it is a rare manifestation, clinicians should consider this a possible differential diagnosis of parotid masses in patients with a history of rheumatoid arthritis or connective tissue disease. | |
32933547 | Patients' and rheumatologists' perceptions on preventive intervention in rheumatoid arthri | 2020 Sep 15 | BACKGROUND: Individuals at risk of developing rheumatoid arthritis (RA) may benefit from lifestyle or pharmacological interventions aimed at primary prevention. The same may apply to individuals at risk of axial spondyloarthritis (axSpA). Our aim was to investigate and compare the willingness of individuals at risk of RA or axSpA and rheumatologists to initiate preventive intervention. METHODS: Individuals at risk of RA (arthralgia and anti-citrullinated protein antibodies and/or rheumatoid factor positivity without arthritis (RA-risk cohort; n = 100)), axSpA (first-degree relatives of HLA-B27-positive axSpA patients (SpA-risk cohort; n = 38)), and Dutch rheumatologists (n = 49) completed a survey on preventive intervention which included questions about disease perception, lifestyle intervention, and preventive medication. RESULTS: At-risk individuals reported willingness to change median 7 of 13 lifestyle components in the areas of smoking, diet, and exercise. In contrast, 35% of rheumatologists gave lifestyle advice to ≥ 50% of at-risk patients. The willingness to use 100% effective preventive medication without side effects was 53% (RA-risk), 55% (SpA-risk), and 74% (rheumatologists) at 30% disease risk which increased to 69% (RA-risk) and 92% (SpA-risk and rheumatologists) at 70% risk. With minor side effects, willingness was 26%, 29%, and 31% (at 30% risk) versus 40%, 66%, and 76% (at 70% risk), respectively. CONCLUSIONS: Risk perception and willingness to start preventive intervention were largely similar between individuals at risk of RA and axSpA. Although the willingness to change lifestyle is high among at-risk individuals, most rheumatologists do not advise them to change their lifestyle. In contrast, rheumatologists are more willing than at-risk patients to start preventive medication. | |
31833613 | Diosmetin exhibits anti-proliferative and anti-inflammatory effects on TNF-α-stimulated h | 2020 Jun | Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation and proliferation of synovial tissues. Diosmetin is a bioflavonoid possessing an anti-inflammatory property. Herein, we aimed to study the effects of diosmetin on the inflammation and proliferation of RA fibroblast-like synoviocytes MH7A cells. MH7A cell proliferation was measured using cell counting kit-8 assay. Cell apoptosis was examined using flow cytometry. The production of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, and matrix metalloproteinase-1 (MMP-1) was measured using enzyme-linked immunosorbent assay (ELISA). Results showed that diosmetin inhibited tumor necrosis factor-α (TNF-α)-induced proliferation increase in MH7A cells in a dose-dependent manner. Diosmetin treatment resulted in an increase in apoptotic rates and a reduction in TNF-α-induced production of IL-1β, IL-6, IL-8, and MMP-1 in MH7A cells. Furthermore, diosmetin inhibited TNF-α-induced activation of protein kinase B (Akt) and nuclear factor-κB (NF-κB) pathways in MH7A cells. Suppression of Akt or NF-κB promoted apoptosis and inhibited TNF-α-induced proliferation increase and production of IL-1β, IL-6, IL-8, and MMP-1 in MH7A cells, and diosmetin treatment enhanced these effects. Taken together, these findings suggested that diosmetin exhibited anti-proliferative and anti-inflammatory effects via inhibiting the Akt and NF-κB pathways in MH7A cells. | |
32708046 | Lysyl Oxidase (LOX): Functional Contributions to Signaling Pathways. | 2020 Jul 22 | Cu-dependent lysyl oxidase (LOX) plays a catalytic activity-related, primary role in the assembly of the extracellular matrix (ECM), a dynamic structural and regulatory framework which is essential for cell fate, differentiation and communication during development, tissue maintenance and repair. LOX, additionally, plays both activity-dependent and independent extracellular, intracellular and nuclear roles that fulfill significant functions in normal tissues, and contribute to vascular, cardiac, pulmonary, dermal, placenta, diaphragm, kidney and pelvic floor disorders. LOX activities have also been recognized in glioblastoma, diabetic neovascularization, osteogenic differentiation, bone matrix formation, ligament remodeling, polycystic ovary syndrome, fetal membrane rupture and tumor progression and metastasis. In an inflammatory context, LOX plays a role in diminishing pluripotent mesenchymal cell pools which are relevant to the pathology of diabetes, osteoporosis and rheumatoid arthritis. Most of these conditions involve mechanisms with complex cell and tissue type-specific interactions of LOX with signaling pathways, not only as a regulatory target, but also as an active player, including LOX-mediated alterations of cell surface receptor functions and mutual regulatory activities within signaling loops. In this review, we aim to provide insight into the diverse ways in which LOX participates in signaling events, and explore the mechanistic details and functional significance of the regulatory and cross-regulatory interactions of LOX with the EGFR, PDGF, VEGF, TGF-β, mechano-transduction, inflammatory and steroid signaling pathways. | |
32252806 | Methotrexate and relative risk of dementia amongst patients with rheumatoid arthritis: a m | 2020 Apr 6 | BACKGROUND: Inflammatory processes have been shown to play a role in dementia. To understand this role, we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk. METHODS: A retrospective matched case-control study of patients over 50 with rheumatoid arthritis (486 dementia cases and 641 controls) who were identified from electronic health records in the UK, Spain, Denmark and the Netherlands. Conditional logistic regression models were fitted to estimate the risk of dementia. RESULTS: Prior methotrexate use was associated with a lower risk of dementia (OR 0.71, 95% CI 0.52-0.98). Furthermore, methotrexate use with therapy longer than 4 years had the lowest risk of dementia (odds ratio 0.37, 95% CI 0.17-0.79). Sulfasalazine use was not associated with dementia (odds ratio 0.88, 95% CI 0.57-1.37). CONCLUSIONS: Further studies are still required to clarify the relationship between prior methotrexate use and duration as well as biological treatments with dementia risk. | |
31729189 | Safety of baricitinib in East Asian patients with moderate-to-severe active rheumatoid art | 2020 Jan | AIM: We evaluated the safety of baricitinib in an East Asian (EA) patient population with moderate-to-severely active rheumatoid arthritis (RA), through an integrated sub-analysis of data from the overall baricitinib RA clinical program. METHODS: Data from EA patients who received any dose of baricitinib from five completed studies (1 Phase 2, 4 Phase 3) and an ongoing long-term extension study were pooled up to 1 September, 2016. Exposure-adjusted incidence rates (EAIR) and incidence rates (IRs), both per 100 patient-years (PY), were calculated. RESULTS: This analysis included 740 EA patients with 1294 PY of total baricitinib exposure (maximum 3.5 years). Overall, 109 patients discontinued baricitinib due to adverse events (AEs); EAIR: 8.4. No deaths were reported in this cohort. Serious AEs were reported by 125 patients (EAIR: 9.7). Serious infections were the most common serious AEs (n = 53, IR: 4.15). IR of herpes zoster infection was 6.2; the majority of events were of mild-to-moderate severity. Three cases (IR: 0.23) of tuberculosis were reported. The IRs of malignancy (excluding non-melanoma skin cancer) was 0.99 and EAIR specifically of lymphoma was 0.1. The IR of major adverse cardiovascular events was 0.26, and deep vein thrombosis was reported in four patients (EAIR: 0.3). Two cases of gastrointestinal perforations (EAIR: 0.2) were reported. CONCLUSION: Integrated data show that baricitinib is well-tolerated in EA patients with moderate-to-severely active RA in the context of demonstrated efficacy, which is generally consistent with safety results of the overall study population. | |
32683326 | Considerations for improving quality of care of patients with rheumatoid arthritis and ass | 2020 Jul | OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with a global prevalence of approximately 0.5-1%. Patients with RA are at an increased risk of developing comorbidities (eg, cardiovascular disease, pulmonary disease, diabetes and depression). Despite this, there are limited recommendations for the management and implementation of associated comorbidities. This study aimed to identify good practice interventions in the care of RA and associated comorbidities. METHODS: A combination of primary research (180+ interviews with specialists across 12 European rheumatology centres) and secondary research (literature review of existing publications and guidelines/recommendations) were used to identify challenges in management and corresponding good practice interventions. Findings were prioritised and reviewed by a group of 18 rheumatology experts including rheumatologists, comorbidity experts, a patient representative and a highly specialised nurse. RESULTS: Challenges throughout the patient pathway (including delays in diagnosis and referral, shortage of rheumatologists, limited awareness of primary care professionals) and 18 good practice interventions were identified in the study. The expert group segmented and prioritised interventions according to three distinct stages of the disease: (1) suspected RA, (2) recent diagnosis of RA and (3) established RA. Examples of good practice interventions included enabling self-management (self-monitoring and disease management support, for example, lifestyle adaptations); early arthritis clinic; rapid access to care (online referral, triage, ultrasound-guided diagnosis); dedicated comorbidity specialists; enhanced communication with primary care (hotline, education sessions); and integrating patient registries into daily clinical practice. CONCLUSION: Learning from implementation of good practice interventions in centres across Europe provides an opportunity to more widely improved care for patients with RA and associated comorbidities. | |
32081915 | The outcomes of bariatric surgery on rheumatoid arthritis disease activity: a prospective | 2020 Feb 21 | Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects the joints. Overweight and obesity can aggravate disease activity and clinical outcome in patients with RA. However, the role of bariatric surgery in inducing weight loss in the treatment of RA has not been confirmed. In this 12-month prospective cohort study, RA patients with obesity who were referred to our hospital were included. Thirty-two patients were classified into the bariatric surgery group according to the patient's decision after a comprehensive assessment of surgery indications, and 33 patients received only pharmacotherapy for RA. At the 12-month follow-up, the response rates of ACR20, ACR50 and ACR70 were 75.0% vs. 51.5%, 53.1% vs. 39.4% and 31.3% vs. 21.2% in the bariatric surgery and non-surgery groups, respectively (all p < 0.05); the mean DAS28-ESR, DAS28-CRP and cDAI scores were 1.5 ± 0.9 vs. 2.4 ± 1.4, 1.2 ± 0.9 vs. 2.2 ± 1.7 and 9.5 ± 6.8 vs. 15.8 ± 12.5, respectively, in surgical patients compared to non-surgical patients (all p < 0.05). Compared to baseline, after 12 months, a significant reduction was observed in the use of leflunomide, biological agents, combination treatments, and NSAIDs in both groups (p < 0.05 or p < 0.01). However, there was no difference in medication use between the 2 groups either at baseline or at the 12-month follow-up (all p > 0.05). Compared to non-surgical patients, in RA patients with obesity, weight loss after bariatric surgery was associated with lower disease activity. Medication tapering for RA in patients who underwent bariatric surgery was not superior to that in non-surgical patients. | |
34756311 | Systematic review of the impact of drugs on diffuse interstitial lung disease associated w | 2021 Nov | OBJECTIVE: To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD). METHODS: Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed. RESULTS: 1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors. CONCLUSIONS: There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such us TNFi, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA. | |
31974480 | First in man study of [(18)F]fluoro-PEG-folate PET: a novel macrophage imaging technique t | 2020 Jan 23 | Non-invasive imaging of arthritis activity in rheumatoid arthritis (RA) patients using macrophage PET holds promise for early diagnosis and therapeutic response monitoring. Previously obtained results with macrophage tracer (R)-[(11)C]PK11195 were encouraging, but the imaging signal could be further improved by reduction of background uptake. Recently, the novel macrophage tracer [(18)F]fluoro-PEG-folate was developed. This tracer showed excellent targeting of the folate receptor β on activated macrophages in synovial tissue in a preclinical arthritic rat model. We performed three substudies to investigate the biodistribution, potential for imaging arthritis and kinetic properties of [18F]fluoro-PEG-folate in RA patients. Firstly, biodistribution demonstrated fast clearance of [(18)F]fluoro-PEG-folate from heart and blood vessels and no dose limiting uptake in organs. Secondly, [(18)F]fluoro-PEG-folate showed uptake in arthritic joints with significantly lower background and hence significantly higher target-to-background ratios as compared to reference macrophage tracer (R)-[(11)C]PK11195. Lastly, dynamic scanning demonstrated fast tracer uptake in affected joints, reaching a plateau after 1 minute, co-existing with a rapid blood clearance. In conclusion, this first in man study demonstrates the potential of [(18)F]fluoro-PEG-folate to image arthritis activity in RA with favourable imaging characteristics of rapid clearance and low background uptake, that allow for detection of inflammatory activity in the whole body. | |
33159312 | Patients with pemphigus are at an increased risk of developing rheumatoid arthritis: a lar | 2020 Dec | Data regarding the association between pemphigus and rheumatoid arthritis (RA) is inconclusive and yet to be firmly established. In the current study, we aimed to evaluate the risk of developing RA during the course of pemphigus. A large-scale population-based longitudinal cohort study was conducted to evaluate the hazard ratio (HR) of RA among 1985 patients with pemphigus relative to 9874 age-, sex-, and ethnicity-matched control subjects. A multivariate Cox regression model was utilized. The incidence of RA was 1.07 (95% CI, 0.62-1.72) and 0.36 (95% CI, 0.24-0.52) per 1000 person-years among patients with pemphigus and controls, respectively. The lifetime prevalence of RA was 2.3% (95% CI, 1.7-3.1%) among cases and 1.8% (95% CI, 1.5-2.0%) among controls. Patients with pemphigus were more than twice as likely to develop RA as compared to control subjects (adjusted HR, 2.54; 95% confidence interval [CI], 1.31-4.92). The increased risk was robust to a sensitivity analysis that included only cases managed by pemphigus-related systemic medications (adjusted HR, 2.56; 95% CI, 1.30-5.05). In conclusion, pemphigus is associated with an increased risk of RA. Physicians treating patients with pemphigus should be aware of this possible association. Further research is required to better understand the mechanism underlying this association. |