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ID PMID Title PublicationDate abstract
34536622 Engineered glove to evaluate hand disability in rheumatoid arthritis: A pilot-study. 2022 Jan OBJECTIVE: The Hand Test System (HTS) is an engineered-sensorized glove that has been originally developed in the neuroscientific field for the evaluation of hand fingers' speed movement. This pilot-study aimed to evaluate the reproducibility of HTS analysis in rheumatoid arthritis (RA), correlating glove-derived parameters with clinical disease activity indexes, self-reported disability-related questionnaires and hand strength. METHODS: Fifty-five RA patients and fifty age and sex matched healthy controls (HCs) performed HTS analysis. The glove recognized the touch speed between the finger tips during standard sequences of movements, providing three quantitative parameters: touch duration (TD), inter-tapping interval (ITI) and movement rate (MR). These variables were correlated with Health Assessment Questionnaire (HAQ), Health Assessment Questionnaire-Disease Index (HAQ-DI), Hand Disability Index (HDI), Hand Grip Strength (HGS), DAS28-CRP, CDAI and SDAI. RESULTS: Intraclass correlation coefficient was 0.93 (CI: 0.92, 0.95). RA patients showed significantly slower TD, ITI and MR than HCs, for all classes of disease activity (P<0.001). All HTS parameters correlated significantly with HAQ, HAQ-DI, HDI, HGS, DAS28-CRP, SDAI, CDAI (between P<0.05 and P<0.001). Of note, also RA patients in clinical remission showed a significantly higher TD compared with HCs (P<0.001). CONCLUSION: HTS seems a new safe and fast tool to evaluate rheumatoid hand's functionality, measuring the speed of finger movements. Furthermore, the HTS parameters significantly correlate with quality of life, disease activity, hand strength and perceived hand disability, evaluating also potential hand motor impairment in RA clinical remission.
34936935 Methotrexate-loaded folic acid of solid-phase synthesis conjugated gold nanoparticles targ 2022 Mar 1 PURPOSE: Methotrexate (MTX) is a first-line drug for rheumatoid arthritis (RA). Targeting of MTX to inflamed joints is essential to the prevention of potential toxicity and improving therapeutic effects. Gold nanoparticles (GNPs) are characterized by controllable particle sizes and good biocompatibilities, therefore, they are promising drug delivery systems. We aimed at developing a GNPs drug delivery system incorporating MTX and folic acid (FA) with strong efficacies against RA. METHODS: MTX-Cys-FA was synthesized through solid-phase organic synthesis. Then, it was coupled with sulfhydryl groups in GNPs, thereby successfully preparing a GNPs/MTX-Cys-FA nanoconjugate with targeting properties. Physical and chemical techniques were used to characterize it. Moreover, we conducted its stability, release, pharmacokinetics, biodistribution and cell cytotoxicity, cell uptake, cell migration, as well as its therapeutic effect on CIA rats. The histopathology was conducted to investigate anti-RA effects of GNPs/MTX-Cys-FA nanoconjugates. RESULTS: The GNPs/MTX-Cys-FA nanoconjugate exhibited a spherical appearance, had a particle size of 103.06 nm, a zeta potential of -33.68 mV, drug loading capacity of 11.04 %, and an encapsulation efficiency of 73.61%. Cytotoxicity experiments revealed that GNPs had good biocompatibilities while GNPs/MTX-Cys-FA exhibited excellent drug-delivery abilities. Cell uptake and migration experiment showed that nanoconjugates containing FA by LPS activated mouse mononuclear macrophages (RAW264.7) was significantly increased, and they exerted significant inhibitory effects on human fibroblast-like synoviocytes (HFLS) of RA (p<0.01). In addition, the nanoconjugate prolonged blood circulation time of MTX in collagen-induced arthritis (CIA) rats (p<0.01), enhanced MTX accumulation in inflamed joints (p<0.01), enhanced their therapeutic effects (p<0.01), and reduced toxicity to major organs (p<0.01). CONCLUSION: GNPs/MTX-Cys-FA nanoconjugates provide effective approaches for RA targeted therapeutic strategies.
33594635 Contribution of P2X4 receptor in pain associated with rheumatoid arthritis: a review. 2021 Jun Pain is the most common symptom reported by patients with rheumatoid arthritis (RA) even after the resolution of chronic joint inflammation. It is believed that RA-associated pain is not solely due to inflammation, but could also be attributed to aberrant modifications to the central nervous system. The P2X4 receptor (P2X4R) is an ATP-activated purinergic receptor that plays a significant role in the transmission of information in the nervous system and pain. The involvement of P2X4R during the pathogenesis of chronic inflammatory pain and neuropathic pain is well-established. The attenuation of this receptor alleviates disease pathogenesis and related symptoms, including hyperalgesia and allodynia. Although some studies have revealed the contribution of P2X4R in promoting joint inflammation in RA, how it implicates pain associated with RA at peripheral and central nervous systems is still lacking. In this review, the possible contributions of P2X4R in the nervous system and how it implicates pain transmission and responses were examined.
34767650 First assessment of thermoacoustic tomography for in vivo detection of rheumatoid arthriti 2022 Jan BACKGROUND: The diagnosis of rheumatoid arthritis (RA) is complicated because of the complexity of symptoms and joint structures. Current clinical imaging techniques for the diagnosis of RA have strengths and weaknesses. Emerging imaging techniques need to be developed for the diagnosis or auxiliary diagnosis of RA. PURPOSE: This study aimed to demonstrate the potential of thermoacoustic tomography (TAT) for in vivo detection of RA in the finger joints. METHODS: Finger joints were imaged by a TAT system using three different microwave illumination methods including pyramidal horn antenna, and parallel in-phase and anti-phase microwave illuminations. Both diseased and healthy joints were imaged and compared when the three microwave illumination methods were used. Magnetic resonance imaging (MRI) of all the joints was performed to validate the TAT findings. In addition, two diseased joints were imaged at two time points by the pyramidal horn antenna-based TAT to track/monitor the progression of RA during a time period of 16 months. Three-dimensional (3-D) TAT images of the joints were also obtained. RESULTS: The TAT images of the diseased joints displayed abnormalities in bone and soft tissues compared to the healthy ones. The TAT images by pyramidal horn antenna and in-phase microwave illumination showed high similarity in image appearance, while the anti-phase-based TAT images provided different information about the disease. We found that the TAT findings matched well with the MRI images. The 3-D TAT images effectively displayed the stereoscopic effect of joint lesions. Finally, it was evident that TAT could detect the development of the lesions in 16 months. CONCLUSION: TAT can noninvasively visualize bone lesions and soft tissue abnormalities in the joints with RA. This first in vivo assessment of TAT provides a foundation for its clinical application to the diagnosis and monitoring of RA in the finger joints.
33605067 Semaphorins: From Angiogenesis to Inflammation in Rheumatoid Arthritis. 2021 Sep OBJECTIVE: To study the potential role of semaphorins in the pathogenesis of rheumatoid arthritis (RA). METHODS: Microarray experiments were performed on Affymetrix GeneChip Human Exon 1.0 ST arrays in RA endothelial cells (ECs) and control ECs derived from circulating progenitors. Expression of class 3 and class 4 semaphorins and their receptors in the serum of RA patients and healthy controls was assessed by immunohistochemical analysis in synovial tissue and by enzyme-linked immunosorbent assay. RESULTS: Microarray analysis revealed differential expression of class 3 and class 4 semaphorins and their receptors in RA ECs. Semaphorin 4A (SEMA4A), plexin D1, and neuropilin 1 messenger RNA (mRNA) levels were markedly increased in RA ECs by 1.75-, 2.21-, and 1.68-fold, respectively. Stimulation with tumor necrosis factor (TNF) led to a 2-fold increase in SEMA4A mRNA levels in RA ECs, and deficient SEMA4A expression modified RA EC angiogenic properties. Class 3 and class 4 semaphorins as well as their receptors were overexpressed in RA synovial tissue. A respective 1.30-fold increase and 1.54-fold increase in SEMA4A and SEMA3E, as well as a 24% decrease in SEMA3A, was observed in the serum of RA patients. Serum levels of SEMA4A, SEMA4D, and SEMA3A correlated with levels of inflammation and proangiogenic markers. In 2 independent cohorts of patients with low disease activity or with RA in remission, the presence of SEMA4A identified patients with residual disease activity. CONCLUSION: Gene expression profiling of ECs identified class 3 and class 4 semaphorins as potential biomarkers and therapeutic candidates in RA, with confirmed overexpression in ECs, synovial vessels, and serum, and correlation with validated markers of inflammation and angiogenesis. Thus, semaphorins might be novel and appealing EC-derived inflammatory and proangiogenic targets in RA.
34586102 Filgotinib as rheumatoid arthritis therapy. 2021 Sep Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and progressive disability when inflammation cannot be sufficiently controlled. Despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs), up to 30% of RA patients do not reach or fail to maintain a good response over time. The recent introduction of Janus kinase inhibitors (JAKis) has widened the rheumatologist's armamentarium. Filgotinib, a selective JAK1 inhibitor, has been approved by the European Medicines Agency (EMA) for treatment of RA. Phase II and III studies highlighted filgotinib safety and efficacy in RA patients naive to DMARDs or with inadequate response to csDMARDs and bDMARDs. Filgotinib is administered orally at 200 mg every day. For patients older than 75 years or with moderate to severe renal impairment, a dose of filgotinib 100 mg every day is recommended.
34042666 Serious Gaming and AI Supporting Treatment in Rheumatoid Arthritis. 2021 May 27 This paper presents a complex application for rehabilitation of patients with first and second stage rheumatoid arthritis (RA). The application contains a module for the doctor, for the kinetotherapist, and a module as a game matching the symptoms for each stage of RA. The purpose of this application is to achieve the rehabilitation of the RA hand with support of digital technology and multimodal interaction: leap motion, serious gaming, and neuronal networks. The neural network offers support for patients to perform the exercises at home classifying the correct movement with accuracy of 95%. During the development of the application, various challenges were encountered in terms of populating the database, raising the cubes within the game related to second stage of RA, and the implementation of the neural network. The application was tested by a group of students, resulting in the fact that the degree of mental stress, fatigue in the fingers, wrists and physical exertion were insignificant in most cases.
34750402 Reappraisal of bone scintigraphy as a new tool for the evaluation of disease activity in p 2021 Nov 8 We aimed to compare the reliability of bone scintigraphy (BS) and fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)-derived parameters in the detection of active arthritis in 28-joint areas and evaluate the reliability of joint counts between BS and clinical assessment in patients with rheumatoid arthritis (RA). We enrolled 106 patients (67 in the development group and 39 in the validation groups) with active RA who underwent BS, (18)F-FDG PET/computed tomography (CT), and clinical evaluation of disease activity. We compared the results of BS-derived joint assessment with those of PET-derived and clinical joint assessments. Subsequently we developed a disease activity score (DAS) using BS-positive joints and validated it in an independent group. The number of BS-positive joints in 28-joint areas significantly correlated with the swollen /tender joint counts (SJC/TJC) and PET-derived joint counts. A BS uptake score of 2 (strong positive) was significantly more sensitive compared with a BS uptake score of 1 (weak positive) in detecting a PET-positive joint among the 28-joints. After conducting multivariate analyses including erythrocyte sediment rate (ESR) and patient global assessment (PGA) in addition to BS-derived parameters, BS/DAS was obtained as follows: 0.056 × number of BS-positive joints in 28 joints + 0.012 × ESR + 0.030 × PGA. A significant correlation between BS/DAS and DAS28-ESR was confirmed in the validation group. Strong positive uptake of BS is sensitive and reproducible for the detection of active joints, and can complement the clinical assessment of disease activity in RA.
33390147 The Interplay of Disease Modifying Anti Rheumatic Drugs and Tuberculin Skin Test. 2021 OBJECTIVE: The study was conducted to determine whether synthetic Disease-Modifying Anti Rheumatic Drugs (DMARDs) suppress the latency of Tuberculosis (TB) infection in Rheumatoid Arthritis (RA) patients along with other variables. METHODS: This was done through Tuberculin Skin Test (TST) using purified protein derivative (PPD) in a cohort of RA patients. The TST was taken positive when induration post-PPD injection was ≥ 5mm and negative or anergic when it was < 5mm. We included 100 patients (N = 100). RESULTS: The prevalence of positive TST was 36%, while 64% presented a negative result. Negative TST was significantly associated with steroid usage (39.4%, 95% CI: 28.4%-51.4%). Anergic (TST negative) and non-anergic (TST positive) patients were separated into groups, and a new analysis was conducted with elaboration on DMARDs used. CONCLUSION: The use of steroids was associated with TST negativity, The same is not true with use of methotrexate or other DMARDs. Thus TST should be interpreted with caution, especially before starting biologicals.
34823822 The association between smoking and the development of rheumatoid arthritis: a population- 2021 Dec INTRODUCTION: Smoking is one of the few modifiable risk factors associated with the development of rheumatoid arthritis (RA). Most published data are over 10 years old, and none included Mediterranean populations. We therefore took advantage of primary care routinely collected data to study the association between smoking and the development of RA in the general population of Catalonia, Spain. METHODS: We conducted a case-control study including all patients with a new diagnosis of RA registered in the SIDIAP database between 01/01/2008 and 31/12/2018; and matched them to up to 1:5 controls by age, gender and general practitioner. Smoking was classified by primary care staff into never, ex- or current smoking. Odds Ratios and 95% confidence intervals for the association between current and ex-smoking (compared to never smoking) and RA were estimated using conditional logistic regression adjusted for potential confounders. RESULTS: A total of 13,920 RA cases and 69,535 controls were included. Compared with never smokers, current and ex-smokers were at increased risk of RA, with adjusted OR of 1.28 [95% CI 1.20-1.37] and OR 1.19 [1.12-1.26] respectively. CONCLUSION: Our findings confirm an association between smoking and the risk of developing RA. The effect seems to prevail in the long-term and even in ex-smokers for 2 or more years after smoking cessation. More research is needed on the effects of smoking discontinuation on RA prevention and related outcomes.
34654367 Soluble programmed death molecule 1 (sPD-1) as a predictor of interstitial lung disease in 2021 Oct 15 BACKGROUND: Previous studies have indicated that the programmed death molecule 1 (PD-1) signaling pathway may play a key role in rheumatoid arthritis (RA). However, the pathogenesis of rheumatoid arthritis-related interstitial lung disease (RA-ILD) is not clear. We examined the serum levels of soluble PD-1 in patients with RA and its relationship with RA-ILD. METHODS: Blood samples were obtained from 87 patients with RA (58 with ILD and 29 without ILD) and 45 healthy controls. Serum sPD-1 was measured by Enzyme-Linked Immunosorbent Assay. The pulmonary interstitial disease score was completed by a pulmonary physician and a radiologist through chest high-resolution computed tomography. Patients with RA-ILD were tested for lung function [e.g., forced vital capacity (FVC%), diffusing capacity of lungs for carbon monoxide (DLCO%)]. Associations between ILD and various markers, including sPD-1 and confounding factors, were investigated by logistic regression analysis. Diagnostic values of sPD-1 for the presence of ILD were investigated using receiver operating characteristic curve analysis. RESULTS: Serum sPD-1 levels were higher in RA patients with ILD than in RA patients without ILD and healthy controls (185.1 ± 109.0 pg/ml vs. 119.1 ± 77.5 pg/ml vs. 52.1 ± 21.7 pg/ml, P < 0.05). Serum sPD-1 levels were positively correlated with RF titer (P = 0.02, r = 0.249), anti-cyclic citrullinated peptide antibody status (P = 0.02, r = 0.243), and serum IgG levels (P < 0.001, r = 0.368), negatively associated with FVC% (P = 0.02, r = - 0.344), forced expiratory volume (FEV1%) (P  = 0.01, r = - 0.354), total lung capacity (TLC%) (P = 0.046, r = - 0.302), and was independently associated with the presence of ILD in RA patients by multivariate logistic regression analysis. The sensitivity and specificity of sPD-1 levels for the detection of ILD in RA patients were 58.6% and 75.9%, respectively. The area under the curve was 0.689. CONCLUSION: Serum sPD-1 levels were increased in RA patients with ILD. Increased sPD-1 may be a valuable biomarker to predict the presence of ILD in patients with RA.
34091255 The emerging role of Interleukin 37 in bone homeostasis and inflammatory bone diseases. 2021 Sep Interleukin 37 (IL-37) is a newly identified cytokine that belongs to the IL-1 family. Unlike other members of the IL-1 family, it has been demonstrated that IL-37 possesses anti-inflammatory characteristics in both innate and acquired immune responses. Recently, significant progress has been made in understanding the role of IL-37 in inflammatory signaling pathways. Meanwhile, IL-37 has also attracted more and more attention in bone homeostasis and inflammatory bone diseases. The latest studies have revealed that IL-37 palys an essential role in the regulation of osteoclastogenesis and osteoblastogenesis. The levels of IL-37 are abnormal in patients with inflammatory bone diseases such as rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and periodontitis. In addition, in vivo studies have further confirmed that recombinant IL-37 treatment displayed therapeutic potential in these diseases. The present review article aims to provide an overview describing the biological functions of IL-37 in bone homeostasis and inflammatory bone diseases, thus shedding new light on a novel therapeutic strategy in the future.
34246888 Causal association of monounsaturated fatty acids with rheumatoid arthritis but not osteoa 2021 Nov OBJECTIVES: Previous studies have indicated that dietary monounsaturated fatty acids (MUFAs) are associated with decreased risk of osteoarthritis (OA) and rheumatoid arthritis (RA). However, the causality of the observed associations is largely undetermined. We sought to ascertain the potential causal roles of two of the most common MUFAs, oleic acid and palmitoleic acid, in RA and OA risk using a two-sample Mendelian randomization approach. METHODS: For the outcomes, we used summary-level data for RA (14 361 people with RA and 43 923 controls) and OA (10 083 people with OA and 40 425 controls) from two genome-wide association studies in European ancestry. For the exposures, five single-nucleotide polymorphisms associated with palmitoleic acid and one associated with oleic acid with genome-wide significance (P < 5 × 10(-8)) were selected as instrumental variables. The causal effects were estimated using the inverse-variance weighted method with several sensitivity analyses. RESULTS: For genetically predicted levels, an increase of one SD in palmitoleic acid (odds ratio, 0.24; 95% confidence interval, 0.10-0.59; P = 0.002) and oleic acid (odds ratio, 0.78; 95% confidence interval, 0.67-0.90; P < 0.001) was significantly associated with lower risk of RA. However, genetic predisposition to either of the two individual MUFAs was not associated with OA risk. Sensitivity analyses yielded similar results. CONCLUSIONS: Our Mendelian randomization analyses suggest a causal relationship between higher genetically predicted MUFA levels and lower risks of RA. However, the causality between MUFAs and OA cannot be inferred from this study. Further research is required to unravel the role of MUFA supplementation in arthritis prevention.
33253889 The role of stromal cell-derived factor 1 on cartilage development and disease. 2021 Mar Stromal cell-derived factor 1 (SDF-1), also known as CXC motif chemokine ligand 12 (CXCL12), is recognized as a homeostatic cytokine with strong chemotactic potency. It plays an important role in physiological and pathological processes, such as the development of multiple tissues and organs, the regulation of cell distribution, and tumour metastasis. SDF-1 has two receptors, CXC chemokine receptor type 4 (CXCR4) and CXC chemokine receptor type 7 (CXCR7). SDF-1 affects the proliferation, survival, differentiation and maturation of chondrocytes by binding to CXCR4 on chondrocytes. Therefore, SDF-1 has been used as an exogenous regulatory target in many studies to explore the mechanism of cartilage development. SDF-1 is also a potential therapeutic target for osteoarthritis (OA) and rheumatoid arthritis (RA), because of its role in pathological initiation and regulation. In addition, SDF-1 shows potent capacity in the repair of cartilage defects by recruiting endogenous stem cells in a cartilage tissue engineering context. To summarize the specific role of SDF-1 on cartilage development and disease, all articles had been screened out in PubMed by May 30, 2020. The search was limited to studies published in English. Search terms included SDF-1; CXCL12; CXCR4; chondrocyte; cartilage; OA; RA, and forty-seven papers were studied. Besides, we reviewed references in the articles we searched to get additional relevant backgrounds. The review aims to conclude the current knowledge regarding the physiological and pathological role of SDF-1 on the cartilage and chondrocyte. More investigations are required to determine methods targeted SDF-1 to cartilage development and interventions to cartilage diseases.
34836709 Integrative pharmacology powers the detection of active components and mechanism underlyin 2022 Feb 5 In China, Wang Bi Granule (WBG)(2), composed of 16 herbal and 1 animal-based compounds, is used for clinical treatment of the "Wang Bi" syndrome, commonly referred to as later rheumatoid arthritis (RA) in modern medicine. It is also used in the treatment of ankylosing spondylitis, tuberculous arthritis, and Kashin-Beck disease, which are characterized by joint pain and swelling deformation. However, its pharmacological mechanisms remain unknown. We aimed to characterize the chemical components in WBG and examine the underlying mechanism for RA treatment using integrative pharmacological strategy, including chemical composition detection, efficacy evaluation, and mechanism exploration. We employed UPLC-QTOF-MS/MS to describe the chemical profile of WBG. TNF-α-stimulated RAW264.7 cells were used to simulate the inflammatory processes in RA and evaluate the anti-inflammatory effects of WBG. Network pharmacology was used to determine the mechanism underlying WBG action in RA. A total of 278 chemical components were identified or tentatively characterized. The water extract of WBG improved the imbalance in inflammation in TNF-α-stimulated RAW264.7 cells by regulating 179 differential genes. 55 key active constituents were obtained based on the interactions among "components" targets, RA-related genes, and differential genes (WBG vs TNF-α group) which may ameliorate RA by regulating 161 hub genes primarily involved in inflammation-related pathways. The present study, for the first time, employed integrative pharmacology to characterize the chemical profile of WBG and elucidate its mechanism of action against RA through an inflammation-immune regulatory system.
34839259 Anti-arthritic activity of the flavonoids fraction of ivy leaves (Hedera helix L.) standar 2022 Jan Ivy leaves (Hedera helix) is a traditional plant used for common cold, cough, and bronchial disorders and can be used for rheumatoid arthritis (RA) as an attempt in alternative medicine. RA is a chronic autoimmune disease characterized by its increasing frequency and adverse consequences. There is an urgent need for a long-term therapy that has favorable biological effects and is less expensive than the already authorized synthetic medicines. This study aimed to determine the anti-arthritic potentials of Hedera helix with determination of the bioactive fraction and discovery of its second-generation metabolites by means of LC/MS. The total ivy ethanolic extract (TIE-E), saponins fraction (Sap-F) and flavonoids fraction (Flav-F) were investigated for their in-vitro anti-arthritic effects and in-vivo by Adjuvant-induced arthritis (AIA) using Complete Freund's Adjuvant (0.1 mL, CFA) intradermal relative to the usual dose of ibuprofen (5 mg/kg). We examined the physical alterations, rheumatoid biomarkers, cytokines that cause and inhibit inflammation, markers of oxidative stress, hyaluronidase and β-glucuronidase enzyme activity. Each paw's histopathology was also evaluated. The chemical profiles of TIE-E were studied using LC/MS in both positive and negative ionization modes. TIE-E (200 mg/kg) and Flav-F (100 mg/kg) significantly (P < 0.05) lowered the edema of the paws, serum immunological indicators, inflammatory cytokines, degenerative enzymes, and indicators of reactive oxygen species with increasing in the anti-inflammatory cytokines. Our findings suggest that extracts of ivy leaves might be used effectively to treat rheumatoid arthritis, where its flavonoid content is responsible for that, and it is able to repress biochemical, oxidative, and pathological changes associated with (AIA) Adjuvant-induced arthritis.
34046798 Current jakinibs for the treatment of rheumatoid arthritis: a systematic review. 2021 Jun OBJECTIVE: One-third of patients with severe rheumatoid arthritis (RA) do not achieve remission or low disease activity, or they have side effects from cDMARD and bDMARD. They will need a new treatment option such as the small molecule JAK inhibitors. In this systematic review, we evaluate the efficacy and safety data of the current jakinibs: tofacitinib, peficitinib, decernotinib, upadacitinib, baricitinib and filgotinib in patients in whom treatment with conventional or biological disease-modifying antirheumatic drugs (cDMARD and/or bDMARD) failed. METHODS: We searched for randomized controlled trials comparing efficacy and safety of jakinibs for RA treatment using the Web of Science, Scopus, PubMed, and clinicaltrials.gov databases with the terms: "rheumatoid arthritis" OR "arthritis rheumatoid" OR "RA" AND "inhibitor" OR "jak inhibitor" AND "clinical trial" OR "treatment" OR "therapy". RESULTS: All jakinibs achieved good results in ACR 20, 50, 70 and with CRP-DAS28 for LDA and remission, upadacitinib showed better results compared to the others. In ESR-DAS28 for remission, tofacitinib achieved the best result. Regarding the safety of all jakinibs, peficitinib, baricitinib and filgotinib did not register deaths in their studies unlike tofacitinib that presented 11 deaths. Despite all benefits of jakinibs, the use in patients with severe liver and kidney disease should be avoided. CONCLUSIONS: Jakinibs in monotherapy or in combination with methotrexate can be considered a viable alternative in the treatment of moderate-to-severe RA. Even after failures with combination of cDMARDS and bDMARDS, jakinibs demonstrated efficacy.
33337986 Histone deacetylase 1 is increased in rheumatoid arthritis synovium and promotes synovial 2021 Sep OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease featured by synovial joint inflammation. Increasing evidence has highlighted microRNAs (miRNAs) and histone deacetylase 1 (HDAC1) as active participants in RA progression. Hence, the present study aims to explore the functions of HDAC1 and miR-124 on synovial cell hyperplasia and synovial inflammation in RA. METHODS: The expression of HDAC1, miR-124 and MARCKS was determined in the synovial tissues collected from 25 RA patients by RT-qPCR and Western blot analysis. Next, a mouse model with collagen-induced arthritis (CIA) was established, from which fibroblast-like synovial cells (FLSs) were isolated. Then the effect of HDAC1, miR-124 and MARCKS on synovial cell hyperplasia and synovial inflammation in CIA mice was evaluated by HE staining, ELISA, and EdU assays. Afterwards, the interaction among HDAC1, miR-124, MARCKS and the JAK/STAT signalling pathway was assessed by ChIP and dual luciferase reporter assay. Finally, the effect of HDAC1 on RA was further verified by establishing a CIA mouse model. RESULTS: HDAC1 was highly expressed and miR-124 and MARCKS were poorly expressed in synovial tissues of CIA. Silencing HDAC1 inhibited synovial cell hyperplasia and synovial inflammation by elevating MARCKS and miR-124 both in vitro and in vivo. Deficiency of HDAC1 promoted H3 and H4 acetylation of miR-124 and MARCKS promoter region. miR-124 alleviated synovial cell hyperplasia and synovial inflammation by repressing the JAK/STAT signalling pathway in CIA. CONCLUSIONS: To sum up, silencing HDAC1 mitigates synovial cell hyperplasia and synovial inflammation in mice with CIA by elevating miR-124 and MARCKS expression, thus highlighting a promising competitive new target for RA treatment.
31961494 Conversion of Functional Assessment of Chronic Illness Therapy-Fatigue to Patient-Reported 2021 Apr OBJECTIVE: The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is validated for measuring fatigue in rheumatoid arthritis (RA). However, 10 of 13 FACIT-F items are identified as relevant to patients with RA. The Patient-Reported Outcomes Measurement Information System (PROMIS) uses an item response theory-calibrated T score metric. The PROMIS Fatigue item bank includes the FACIT-F items, enabling score conversion. The performance of converted PROMIS Fatigue scores has not been evaluated in RA populations or clinical trials. Our objective was to assess the performance of converted PROMIS Fatigue scores in 2 RA clinical trials of baricitinib. METHODS: Crosswalk tables and pattern-scoring methods converted FACIT-F scores to PROMIS Fatigue for both the 13-item FACIT-F and the 10-item RA-optimized FACIT-F instrument, in 2 RA clinical trials evaluating baricitinib, RA-BEAM, and RA-BEACON. RA-BEAM patients had an inadequate response to methotrexate. RA-BEACON patients had an inadequate response or intolerance to ≥1 tumor necrosis factor inhibitor. Baricitinib was compared to all treatment arms via analysis of covariance on PROMIS Fatigue score conversions. RESULTS: Baseline FACIT-F-derived PROMIS Fatigue scores reflected severe fatigue across treatment groups and were similar using different scoring methods. At week 24 in both studies, baricitinib was associated with clinically meaningful improvements in PROMIS Fatigue scores. PROMIS Fatigue scores were consistent for conversion methods and for the 13-item or 10-item FACIT-F. CONCLUSION: All 4 conversion methods showed differentiation of active treatment compared with placebo from week 12, supporting the use of the PROMIS Fatigue and converting the 10-item FACIT-F to assess fatigue and demonstrate treatment benefit in RA clinical trials on a standardized metric.
34213524 The efficacy of systemic glucocorticosteroids for pain in rheumatoid arthritis: a systemat 2021 Dec 24 OBJECTIVES: Glucocorticosteroids (GCs) are recommended to suppress inflammation in people with active RA. This systematic review and meta-analysis aimed to quantify the effects of systemic GCs on RA pain. METHODS: A systematic literature review of randomized controlled trials (RCTs) in RA comparing systemic GCs to inactive treatment. Three databases were and spontaneous pain and evoked pain outcomes were extracted. Standardized mean differences (SMDs) and mean differences were meta-analysed. Heterogeneity (I2, tau statistics) and bias (funnel plot, Egger's test) were assessed. Subgroup analyses investigated sources of variation. This study was pre-registered (PROSPERO CRD42019111562). RESULTS: A total of 18 903 titles, 880 abstracts and 226 full texts were assessed. Thirty-three RCTs suitable for the meta-analysis included 3123 participants. Pain scores (spontaneous pain) decreased in participants treated with oral GCs; SMD = -0.65 (15 studies, 95% CI -0.82, -0.49, P <0.001) with significant heterogeneity (I2 = 56%, P =0.0002). Efficacy displayed time-related decreases after GC initiation. Mean difference visual analogue scale pain was -15 mm (95% CI -20, -9) greater improvement in GC than control at ≤3 months, -8 mm (95% CI -12, -3) at >3-6 months and -7 mm (95% CI -13, 0) at >6 months. Similar findings were obtained when evoked pain outcomes were examined. Data from five RCTs suggested improvement also in fatigue during GC treatment. CONCLUSION: Oral GCs are analgesic in RA. The benefit is greatest shortly after initiation and GCs might not achieve clinically important pain relief beyond 3 months. Treatments other than anti-inflammatory GCs should be considered to reduce the long-term burden of pain in RA.