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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| 33928275 | Characteristic-specific rates of rheumatoid arthritis and its management in Australian gen | 2021 May | BACKGROUND AND OBJECTIVES: A 2006-16 study investigated rheumatoid arthritis (RA) management by Australian general practitioners (GPs). The aim of this study was to examine: GP-patient encounters for RA management over the decade, treatments provided for RA management (new and continuing), characteristics of patients managed and of GPs providing management, and differences across regional areas and areas of socioeconomic advantage/disadvantage, compared with Australian guidelines. METHOD: GP self-reported data collected through the Bettering the Evaluation And Care of Health (BEACH) program were analysed for patient and GP characteristics and management actions (medications, referrals, investigations, procedures) nationally, regionally and by socioeconomic advantage/disadvantage levels. RESULTS: Proportions of RA management encounters: remained static across the decade, were higher for female patients, increased with patient and GP age, increased with socioeconomic disadvantage in major cities, were higher for patients from English-speaking backgrounds, and were higher in regional/remote areas. DISCUSSION: GP behaviour indicates equity and uniformity in RA management nationally. The results suggest adherence to current guidelines for total and new RA contacts. | |
| 34994147 | [Xinfeng Capsules promotes apoptosis of synovial fibroblasts and attenuates inflammation i | 2021 Dec | To explore the regulatory effects of Xinfeng Capsules(XFC) on the apoptosis of synovial fibroblasts(FLS) and inflammation in rheumatoid arthritis(RA) via lncRNA MAPKAPK5-AS1(MK5-AS1). Thirty healthy people and 30 patients with RA due to spleen deficiency and dampness exuberance were collected for extracting the peripheral blood mononuclear cells(PBMCs) before and after XFC treatment, which were used to observe the correlation between MK5-AS1 and clinical indicators as well as MK5-AS1 expression before and after XFC treatment. Following the establishment of RA-FLS cell line and the preparation of XFC-containing serum, MK5-AS1-overexpression plasmid was constructed and transfected into RA-FLS for investigating the efficacy of XFC-containing serum in regulating inflammation and apoptosis of RA-FLS via MK5-AS1. The expression of MK5-AS1 in PBMCs of patients with RA due to spleen deficiency and dampness exuberance was decreased(P<0.001). The ROC curve analysis revealed the AUC of 83.9%. Correlation analysis showed that MK5-AS1 was negatively correlated with ESR, CRP, RF, CCP, and spleen deficiency and dampness exuberance syndrome score. The expression of MK5-AS1 increased significantly after XFC treatment(P<0.001). As demonstrated by association analysis, XFC decreased MK5-AS1, ESR, CRP, RF, and spleen deficiency and dampness exuberance syndrome score, with the degree of support all greater than 83%, confidence greater than 80%, and lift greater than 1. The results of RT-qPCR showed that the MK5-AS1 RNA expression significantly decreased after TNF-α stimulation(P<0.01), which, however, increased significantly after the intervention with XFC-containing serum(P<0.05). Such expression rose again after the transfection of pcDNA3.1-MK5-AS1(P<0.01). ELISA results showed that TNF-α stimulation elevated the expression of pro-inflammatory factor IL-17 but lowered the expression of anti-inflammatory factor IL-4(P<0.01). After intervention with XFC-containing serum, the expression of IL-17 decreased while that of IL-4 increased(P<0.01). The transfection of pcDNA3.1-MK5-AS1 contributed to the reduction in IL-17 expression but the elevation in IL-4 expression(P<0.01). The immunofluorescence(IF) findings demonstrated that the expression of pro-apoptotic protein Bax was down-regulated, whereas that of the anti-apoptotic protein Bcl-2 was up-regulated after TNF-α stimulation(P<0.01). After the intervention with XFC-containing serum, the Bax expression was increased, while Bcl-2 expression was decreased(P<0.01), which were remarkably collaborated by the transfection of pcDNA3.1-MK5-AS1(P<0.05). The expression of MK5-AS1 is significantly decreased in both RA-PBMCs and RA-FLS, implying that XFC inhibits inflammatory reaction and promotes the apoptosis in RA by regulating the expression of MK5-AS1. | |
| 35431355 | Effects of nonsurgical periodontal therapy in patients with rheumatoid arthritis: a prospe | 2021 Jul | BACKGROUND: periodontal therapy has been suggested to have systemic effects. However, studies of periodontal therapy in rheumatoid arthritis patients have produced controversial results. AIM: To compare the effects of nonsurgical periodontal therapy on biochemical markers of rheumatoid arthritis and periodontal parameters in patients with and without rheumatoid arthritis. METHODS: a prospective before-and-after study was conducted that included 21 participants without and 29 participants with rheumatoid arthritis. Periodontal parameters, Porphyromonas gingivalis detection, C-reactive protein, rheumatoid factor and anti-citrullinated protein antibodies were measured at baseline and three months after nonsurgical periodontal therapy and the changes were statistically assessed. RESULTS: In general, both groups presented statistically significant improvement in periodontal parameters (p<0.05). There was an increase in the counts of P. gingivalis in both groups at three months. In addition, there was a reduction in levels of anti-citrullinated protein antibodies and rheumatoid factor in participants with rheumatoid arthritis. In contrast, C-reactive protein levels increased in both groups but were higher in the rheumatoid arthritis group. Periodontal parameters in rheumatoid arthritis participants under disease-modifying antirheumatic drugs presented a slightly higher improvement (p <0.05). CONCLUSIONS: Nonsurgical periodontal therapy has similar improvements in periodontal parameters in patients with and without rheumatoid arthritis. In addition, nonsurgical periodontal therapy may benefit serum levels of anti-citrullinated protein antibodies and rheumatoid factors in patients with rheumatoid arthritis. NCT04658615. | |
| 34114403 | Zhuifeng Tougu capsules improve rheumatoid arthritis symptoms in rats by regulating the to | 2021 Jun | OBJECTIVE: To investigate the efficacy of Zhuifeng tougu capsules (, ZFTG) in the treatment of rheumatoid arthritis (RA) in rats and study its mechanism, focusing on the toll-like receptor 2/4-nuclear factor kappa-B (TLR2/4-NF-κB) signaling pathway. METHODS: Type Ⅱ collagen and an artificial climate box were used to construct the rat model of collagen-induced arthritis with wind-cold-dampness arthralgia syndrome. The rats were divided randomly into a control group, wind-cold-dampness syndrome model group, and high-, medium-, and low-dose ZFTG groups. The methotrexate (MTX) control group was treated with the corresponding drug intervention for 28 d. The joint temperature, pain threshold, joint swelling degree, and arthritis index (AI) score were measured. The production of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factors (RFs) in the blood was detected by enzyme-linked immunosorbent assay. The protein expression of TLR2, TLR4, and NF-κB in synovial tissues was detected by Western blotting, and the mRNA expression of TLR2, TLR4, and NF-κB was detected by real-time polymerase chain reaction. RESULTS: Compared with the model group, the joint temperature in each treatment group, the MTX control group, and MTX group recovered, the degree of foot swelling, pain threshold, AI score decreased, serum CRP, ESR, RF level and the levels of TLR2, TLR4, and NF-κB in synovial tissue were decreased (P < 0.05). Among them, the curative effect in the medium-dose and MTX groups was more evident (P < 0.01). CONCLUSION: ZFTG has a significant effect on RA in rats, and its mechanism may involve regulating CRP levels, the ESR, and RFs via the TLR2/4-NF-κB signaling pathway. | |
| 34556105 | Peripheral quantitative computed tomography in the assessment of bone mineral density in a | 2021 Sep 23 | INTRODUCTION: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with osteoporosis. There have not been many peripheral quantitative computed tomography (QCT) studies in patients receiving biologics. We assessed volumetric and areal bone mineral density (BMD) by forearm QCT and dual-energy X-ray absorptiometry (DXA), respectively in addition to laboratory biomarkers in these arthritides. METHODS: Forty RA and AS patients treated with either etanercept (ETN) or certolizumab pegol (CZP) were undergoing follow-ups for one year. Volumetric and areal BMD, as well as parathyroid hormone (PTH), osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin (SOST), Dickkopf 1 (DKK-1) and cathepsin K (CATHK) were determined. RESULTS: We did not observe any further bone loss during the 12-month treatment period. Volumetric and areal BMD showed significant correlations with each other (p<0.017 after Bonferroni's correction). Trabecular QCT BMD at baseline (p=0.015) and cortical QCT BMD after 12 months (p=0.005) were inversely determined by disease activity at baseline in the full cohort. Trabecular QCT BMD at baseline also correlated with CTX (p=0.011). In RA, CRP negatively (p=0.014), while SOST positively (p=0.013) correlated with different QCT parameters. In AS, RANKL at baseline (p=0.014) and after 12 months (p=0.007) correlated with cortical QCT BMD. In the full cohort, 12-month change in QTRABBMD was related to TNF inhibition together with elevated VITD-0 levels (p=0.031). Treatment and lower CATHK correlated with QCORTBMD changes (p=0.006). In RA, TNF inhibition together with VITD-0 (p<0.01) or CATHK-0 (p=0.002), while in AS, treatment and RANKL-0 (p<0.05) determined one-year changes in QCT BMD. CONCLUSIONS: BMD as determined by QCT did not change over one year of anti-TNF treatment. Disease activity, CATHK, RANKL and VITD may be associated with the effects of anti-TNF treatment on QCT BMD changes. RA and AS may differ in this respect. | |
| 33847204 | Clinical pharmacology of filgotinib in the treatment of rheumatoid arthritis: current insi | 2021 Jun | INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease, whose natural course has been deeply modified thanks to the development of new therapeutic approaches. The Janus kinase inhibitors (Jakinibs) represent the newest class of drugs introduced for treating RA. Among these, Filgotinib (FIL) has been developed as Janus kinase1 (JAK1) selective inhibitor, specifically targeting key pro-inflammatory mediators in RA pathogenesis. AREAS COVERED: This narrative review provides an overview on FIL as new therapeutic approach for RA, with focus on its pharmacological properties, clinical efficacy, and safety profile. The following electronic databases were adopted for the study search: PubMed, Google Scholar, ClinicalTrials.gov and Abstract archive from the American College of Rheumatology and the European Alliance of Associations for Rheumatology. EXPERT OPINION: The phase II and phase III randomized controlled trials (RCTs) performed so far and their long-term extensions showed a comparable clinical efficacy of FIL to biologic treatments, with an acceptable safety profile. Thanks to these data, FIL was approved in Europe and Japan for the treatment of active RA, increasing the spectrum of therapeutic approaches and improving the possibility of a more tailored therapeutic strategy. Real-life data and head-to-head clinical trials will be needed to confirm its efficacy and safety. | |
| 33560583 | A qualitative study exploring the experiences and perceptions of patients with rheumatoid | 2021 May | Foot pathology in people with rheumatoid arthritis (RA) can have a psychosocial impact, but interventions such as foot orthoses can reduce foot pain, improving physical activity and quality of life. A previous meta-analysis concluded that foot orthoses can relieve pain and disability and enhance patient's well-being. The aim of this study was to explore the experiences of people with RA, before and after wearing foot orthoses for 6 months. Data were collected through digital recordings of semi-structured interviews carried out before and after wearing foot orthoses for 6 months. A thematic analysis of the transcripts was used to identify themes. Six female participants with RA wore foot orthoses for 6 months in Spain. The mean disease duration was more than 10 years. The findings showed three key themes emerged from the data: (1) improvement in physical activity; (2) footwear… a tricky situation and (3) social implications of RA feet. It is concluded that patients reported that wearing foot orthoses can have a positive impact on physical activity and improve general wellness and quality of life. However, to achieve the potential positive benefits, people with RA also needed to wear suitable footwear (defined as footwear which accommodates both the foot and the insole while maintaining the fit and function of the shoe). Despite the positive impact of wearing orthoses, participants stated that complexities of finding suitable footwear acted as a blocker. | |
| 32339372 | Association of Rheumatoid Arthritis in Pregnancy With School Performance of Offspring: A D | 2021 Jul | OBJECTIVE: To examine the overall cognitive development of children exposed to maternal rheumatoid arthritis (RA) in utero by comparing their school test scores to those of their peers. METHODS: Children born in Denmark during 1995-2008 and listed in the National School Test Register were included (n = 738,862). Children exposed to maternal RA were identified through linkage of national registers. In separate analyses, exposure was subdivided according to maternal serostatus. Preclinical maternal RA was included as a separate exposure. The Danish national school tests are mandatory standardized tests. Results from all reading tests (grades 2, 4, 6, and 8) and mathematics tests (grades 3 and 6) from 2010-2017 were included. Test scores were compared according to maternal RA exposure for each test separately using linear regressions. RESULTS: We identified 934 children exposed to maternal RA in utero. There were no differences in reading test scores between maternal RA exposed and unexposed children. RA exposed children scored poorer in both mathematics tests (adjusted differences of mean score -0.14 SD (95% confidence interval [95% CI] -0.23, -0.06) and -0.16 SD (95% CI -0.26, -0.07). There was no appreciable difference between children by maternal RA serostatus. Children exposed to preclinical RA (n = 589) showed the same pattern of performance as children exposed to RA. CONCLUSION: RA-exposed children scored slightly poorer in mathematics tests but performed as well as their unexposed peers in the reading tests. The results do not suggest that RA in pregnancy has a major impact on offspring school performance. | |
| 33879176 | Effects of illness perceptions on health-related quality of life in patients with rheumato | 2021 Apr 20 | OBJECTIVES: For patients with rheumatoid arthritis (RA) in China, little is known of how their illness perceptions affect their health-related quality of life (HRQoL). The present study investigated associations between specific illness perceptions due to RA and HRQoL features. METHODS: For 191 patients with RA, illness perceptions were measured using the Brief Illness Perceptions Questionnaire (BIPQ) comprising 8 domains. HRQoL was determined with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Multivariate linear regression analyses were performed. RESULTS: The overall BIPQ of patients with RA was 49.09 ± 11.06. The highest and lowest scores were for concern (9.15 ± 1.81) and personal control (4.30 ± 2.52), respectively. Multivariate stepwise regression analyses showed that the overall BIPQ was significantly negatively associated with each HRQoL feature, and HRQoL total score (β = - 0.343, P < 0.001, 95% CI - 7.080 to - 4.077). Positive associations between BIPQ features and HRQoL included personal control (β = 0.119, P = 0.004, 95% CI 2.857-14.194) and treatment control (β = 0.084, P = 0.029, 95% CI 0.640-12.391). Negative associations with HRQoL were identity (β = - 0.105, P = 0.034, 95% CI - 13.159 to - 0.430) and emotional response (β = - 0.207, P < 0.001, 95% CI - 18.334 to - 6.811). CONCLUSIONS: Patients with RA in China perceive their illness in ways that affect their HRQoL. These results suggest that strategies that target these perceptions may improve the quality of life of these patients. | |
| 33244616 | MRI wrist in early rheumatoid arthritis: reduction in inflammation assessed quantitatively | 2021 Jul | OBJECTIVE: To investigate (a) which MR features of inflammation (synovitis, tenosynovitis, perfusion) correlate with clinical/serological features in early rheumatoid arthritis (ERA) before, during and after 1 year of treatment and (b) whether quantitative or semi-quantitative measures of inflammation on magnetic resonance imaging (MRI) provides the highest correlation in this regard. METHOD: One hundred one ERA patients (76 females, 25 males, mean age, 53 ± 12 years) underwent clinical/serological testing and 3 T dynamic contrast-enhanced MRI of the most symptomatic wrist. Seventy-seven of the 101 patients completed 1 year of treatment, followed by repeat MR examination. Clinical/serological parameters were correlated with semi-quantitative/quantitative MR measures of inflammation at baseline, during and after 1 year of treatment. Spearman's correlation was applied. RESULTS: Quantitative measures of inflammation correlated better with clinical/serological parameters than semi-quantitative measures, with the highest correlations being for relative change during treatment. Pain reduction correlated with reduced tenosynovitis volume (r = 0.41). Reduction in disease activity correlated with reduction in synovitis volume (r = 0.66) or synovial perfusion parameters (r = 0.58). Decrease in early morning stiffness correlated with decrease in perfusion parameters (r = 0.46). Reduction in ESR and CRP correlated with decrease in synovial volume (r = 0.40 and r = 0.41, respectively). CONCLUSION: In ERA patients, quantitative assessment of inflammation on MRI correlated better with clinical parameters than semi-quantitative assessment. Relative change during treatment yielded the highest correlation. Decrease in tenosynovitis correlated best with reduction in pain while decrease in synovitis volume and perfusion correlated best with reduction in disease activity, early morning stiffness (perfusion), or serological parameters (synovitis volume). | |
| 33605405 | Should we use glucocorticoids in early rheumatoid arthritis? Results at 5 years from the e | 2021 Dec 1 | OBJECTIVES: To evaluate the proportion of patients with early RA (ERA) who had or had not initiated glucocorticoids, to analyse the baseline characteristics, and to assess the clinical benefit and side effects of glucocorticoids during 5 years of follow-up. METHODS: We included patients with ERA from the UCLouvain Brussels cohort who met the ACR/EULAR 2010 classification criteria and were naïve to conventional DMARDs (cDMARDs). We retrospectively collected patient characteristics prior to the introduction of cDMARDs with or without glucocorticoids. Efficiency and serious adverse events were analysed at 6, 12, 36 and 60 months. RESULTS: Data from 474 eligible ERA patients were collected; 180 patients initiated glucocorticoids compared with 294 who did not. At baseline, the increased CRP was the main factor that favoured the initiation of glucocorticoids followed by smoking, absence of ACPA, prescription of MTX as a monotherapy and age. Five years' follow-up of DAS28-CRP, HAQ or visual analog score (VAS) pain values did not differ between the two groups. We also analysed a subgroup of 139 patients who received >1 g of prednisolone during the 5-year period. We confirmed the same baseline differences and observed in addition more men and higher DAS-28CRP values. During the 5 years' follow-up, DAS-28CRP, VAS pain and HAQ remained significantly higher in this subgroup. More severe infections were also reported. CONCLUSION: In our ERA cohort, the initiation of glucocorticoid treatment did not bring additional benefit for the short- and long-term control of the disease. Glucocorticoid was more prescribed in seronegative RA patients with a higher level of inflammation. | |
| 34581056 | [Therapeutic mechanism of Psammosilene tunicoides extract on rheumatoid arthritis based on | 2021 Sep | In this study, we investigated the mechanism of crude extract of Psammosilene tunicoides(CEPT) in the treatment of rheumatoid arthritis(RA) based on the Nod-like receptor protein 3(NLRP3) inflammasome. The collagen-induced arthritis(CIA) mouse model was established. On day 32 after the primary immunization, according to the arthritis score, the mice were randomly divided into model group, positive control(methotrexate) group, low-and high-dose CEPT groups, and normal group, with 10 mice in each group. According to the administration dose of each group, the mice were continuously administered for 21 days. Every four days during the administration, the paw edema degree, arthritis score, and spleen index of the mice were measured; histopathological examination was performed for the ankles of the mice; the contents of IL-1β and IL-18 in the serum were determined; the protein expression levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a CARD(ASC), as well as the mRNA expression levels of NLRP3 and caspase-1 in the ankle joints of the mice were detected. The results showed that compared with those in the model group, the mice in the positive control group and CEPT groups had significantly decreased the contents of IL-1β and IL-18 in the serum and spleen index(P<0.01), significantly lowered arthritis score and degree of paw edema(P<0.01), alleviated arthritic infiltration of the knee, and down-regulated protein and mRNA levels of NLRP3, ASC, and caspase-1 in the ankle joint(P<0.01). These results suggest that P. tunicoides may reduce the paw edema and arthritis score and alleviate the inflammatory response in CIA mice by inhibiting the expression of NLRP3. This study provides a basis for the study of immune regulation of P. tunicoides in RA. | |
| 33213351 | Ideational Fluency in Patients with Rheumatoid Arthritis. | 2021 | BACKGROUND: Neuropsychiatric symptoms have been well documented in several systemic inflammatory conditions, for example, systemic lupus erythematosus (SLE). Increased prevalence of cognitive decline and psychiatric issues has been reported in patients with rheumatoid arthritis (RA). However, there is limited evidence of which exact cognitive domains are affected and to what degree. AIM: To test the performance of cognition in the domain of ideational fluency (Thing Categories Test in particular) in patients with RA and compare the results with the general population and to the results with cognitive and depression screening scores in both groups. METHODS: Patient Health Questionnaire 9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7) assessment, Montreal Cognitive Assessment (MoCA), and Thing Categories Test (TCT) were used to evaluate patients with RA, as well as the control group. RESULTS: Twenty patients with RA and 20 controls were tested, with 7 and 4 men, and 13 and 16 women in the study and control group, respectively. Average scores in TCT at three minutes were 7.50 (IQR6.0-10.0) and 6.0 (IQR3.0-8.0) for category "blue"; 17.50 (IQR15.0-19.0) and 16.0 (10.0-18.0) for category "round" in the control and study group, respectively. A statistically significant difference was established between the study and the control group in TCT for the category "blue" (p<0.025). The average score for GAD7 was 2.0 (IQR 0.0-5.75) and 3.0 (IQR0.50-6.00) in the control and study group, respectively. The average score for PHQ-9 was 2.0 (IQR0.25-4.75) and 4.0 (IQR2.00-5.50) in the control and study group, respectively. Finally, the average score for the MoCA scale was 27.0 (IQR25.25-28.00) and 26.0 (IQR23.50-28.00) in the control and study group, respectively. CONCLUSION: Preliminary evidence suggests that RA at least partially affects the cognitive domain of ideational fluency. However, further research with larger experimental groups is needed to provide more conclusive evidence. | |
| 33420616 | Computer-aided diagnosis based on hand thermal, RGB images, and grip force using artificia | 2021 Feb | Rheumatoid arthritis (RA) is an autoimmune disorder that typically affects people between 23 and 60 years old causing chronic synovial inflammation, symmetrical polyarthritis, destruction of large and small joints, and chronic disability. Clinical diagnosis of RA is stablished by current ACR-EULAR criteria, and it is crucial for starting conventional therapy in order to minimize damage progression. The 2010 ACR-EULAR criteria include the presence of swollen joints, elevated levels of rheumatoid factor or anti-citrullinated protein antibodies (ACPA), elevated acute phase reactant, and duration of symptoms. In this paper, a computer-aided system for helping in the RA diagnosis, based on quantitative and easy-to-acquire variables, is presented. The participants in this study were all female, grouped into two classes: class I, patients diagnosed with RA (n = 100), and class II corresponding to controls without RA (n = 100). The novel approach is constituted by the acquisition of thermal and RGB images, recording their hand grip strength or gripping force. The weight, height, and age were also obtained from all participants. The color layout descriptors (CLD) were obtained from each image for having a compact representation. After, a wrapper forward selection method in a range of classification algorithms included in WEKA was performed. In the feature selection process, variables such as hand images, grip force, and age were found relevant, whereas weight and height did not provide important information to the classification. Our system obtains an AUC ROC curve greater than 0.94 for both thermal and RGB images using the RandomForest classifier. Thirty-eight subjects were considered for an external test in order to evaluate and validate the model implementation. In this test, an accuracy of 94.7% was obtained using RGB images; the confusion matrix revealed our system provides a correct diagnosis for all participants and failed in only two of them (5.3%). Graphical abstract. | |
| 34269913 | Chronic Pain in Patients with Rheumatoid Arthritis. | 2021 Jul 16 | PURPOSE OF REVIEW: Chronic pain is highly prevalent in patients with rheumatoid arthritis (RA) and can cause various physical and psychological impairments. Unfortunately, the appropriate diagnosis of chronic pain syndromes in this population can be challenging because pain may be primary to RA-specific inflammation and/or secondary to other conditions, typically osteoarthritis (OA) and fibromyalgia (FM). This disparity further poses a clinical challenge, given that chronic pain can often be discordant or undetected with standard RA-specific surveillance strategies, including serological markers and imaging studies. In this review, we provide a robust exploration of chronic pain in the RA population with emphasis on epidemiology, mechanisms, and management strategies. RECENT FINDINGS: Chronic pain associated with RA typically occurs in patients with anxiety, female sex, and elevated inflammatory status. Up to 50% of these patients are thought to have chronic pain despite appropriate inflammatory suppression, typically due to peripheral and central sensitization as well as secondary OA and FM. In addition to the standard-of-care management for OA and FM, patients with RA and chronic pain benefit from behavioral and psychological treatment options. Moreover, early and multimodal therapies, including non-pharmacological, pharmacological, interventional, and surgical strategies, exist, albeit with varying efficacy, to help suppress inflammation, provide necessary analgesia, and optimize functional outcomes. Overall, chronic pain in RA is a difficult entity for both patients and providers. Early diagnosis, improved understanding of its mechanisms, and initiation of early, targeted approaches to pain control may help to improve outcomes in this population. | |
| 33303993 | Why remission is not enough: underlying disease mechanisms in RA that prevent cure. | 2021 Mar | Cure is the aspirational aim for the treatment of all diseases, including chronic inflammatory conditions such as rheumatoid arthritis (RA); however, it has only been during the twenty-first century that remission, let alone cure, has been a regularly achievable target in RA. Little research has been carried out on how to cure RA, and the term 'cure' still requires definition for this disease. Even now, achieving a cure seems to be a rare occurrence among individuals with RA. Therefore, this Review is aimed at addressing the obstacles to the achievement of cure in RA. The differences between remission and cure in RA are first defined, followed by a discussion of the underlying factors (referred to as drivers) that prevent the achievement of cure in RA by triggering sustained immune activation and effector cytokine production. Such drivers include adaptive immune system activation, mesenchymal tissue priming and so-called 'remote' (non-immune and non-articular) factors. Strategies to target these drivers are also presented, with an emphasis on the development of strategies that could complement currently used cytokine inhibition and thereby improve the likelihood of curing RA. | |
| 34412009 | Novel quantitative digital image analysis methodology for assessment of inflammatory chang | 2021 Oct | PURPOSE: To evaluate a novel quantitative methodology to assess inflammatory changes in magnetic resonance imaging (MRI) data from patients with rheumatoid arthritis (RA) and the impact of image quality on imaging outcomes compared to the RA Magnetic Resonance Imaging Score (RAMRIS). METHODS: Three-dimensional, T1-weighted, fat-suppressed MRI sequences of the hand/wrist before and after intravenous Gadolinium contrast from patients with RA in a placebo-controlled clinical trial (NCT01185353) were re-evaluated post hoc. The methodology was integrated into proprietary software (DYNAMIKA®) and assessed inflammation through pixelated measurements of the contrast-enhancing (inflammatory) volume. A semi-automatic approach outlined contrast-enhancing synovial tissue in the wrist and second to fifth metacarpophalangeal joints with a rough region of interest (ROI); quantitative imaging biomarkers were generated by means of quantitative total volume of inflammation and quantitative degree of inflammation relative to the signal in a 1 cm in diameter ROI in the center of the thenar or lumbrical muscle for internal reference. The time from Gadolinium injection to finalization of the post-contrast images was calculated from the images' Digital Imaging and Communications in Medicine header. An experienced reader graded image quality as poor, acceptable, or good. RESULTS: Results from this quantitative methodology, especially when excluding images with poor quality scores (14-32%), provided a more pronounced and monotonically increasing dose-response than the original RAMRIS results on synovitis and osteitis. CONCLUSIONS: This computer-aided quantitative scoring method provided continuous measures of inflammatory changes relative to muscle and may be more sensitive and interpretable concerning dose/response separation between RA treatment groups. | |
| 33803959 | Natural Plant Extracts and Compounds for Rheumatoid Arthritis Therapy. | 2021 Mar 15 | Natural plant extracts and compounds (NPECs), which originate from herbs or plants, have been used in the clinical treatment of rheumatoid arthritis (RA) for many years. Over the years, many scientists have carried out a series of studies on the treatment of RA by NPEC. They found a high quantity of active NPECs with broad application prospects. In view of various complex functions of these NPECs, exploring their potential as medicines for RA treatment will be beneficial for RA patients. Thus, to help advance the development of high-quality NPECs for RA, we herein aimed to review the research progress of NPECs in the treatment of RA in recent years. Our findings showed that, from the pharmacological perspective, natural plant extracts or mixed herbal compounds effectively regulate the immune system to alleviate RA by inhibiting pro-inflammatory cytokines. Further, individualized medication can be applied according to each patient's physical condition. However, the pathogenesis of RA and its immune mechanism has not been fully understood and requires further studies. | |
| 34808131 | LncRNA HOTTIP from synovial fibroblast-derived exosomes: A novel molecular target for rheu | 2021 Dec 15 | Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. HOTTIP, a long noncoding RNA (lncRNA), participates in cell proliferation and invasion. However, the correlation between HOTTIP and RA remains unclear. Therefore, this study aimed to clarify how HOTTIP works in RA and to investigate its role in the development of RA. Flow cytometry was used to analyze cell cycle progression. Binding between HOTTIP, signal transducer and activator of transcription 3 (STAT3) and miR-1908-5p was demonstrated by dual-luciferase assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of T cell differentiation-related proteins. We found that HOTTIP was upregulated in rheumatoid arthritis synovial fibroblasts (RASFs). HOTTIP directly bound to miR-1908-5p and negatively modulated miR-1908-5p expression while positively regulating STAT3. The effects of HOTTIP overexpression on regulating the balance of the Th17/Treg cell ratio were partly reversed by miR-1908-5p overexpression. In addition, in vivo experiments demonstrated that overexpression of HOTTIP aggravated inflammation in RA mice, which was demonstrated by hematoxylin and eosin (HE) staining and the increased expression levels of CD4(+) interleukin (IL)-17(+), forkhead Box P3 (FOXP3) and retinoid-related orphan receptor gamma-t (RORγt). In summary, our study suggests that HOTTIP plays a damaging role in RA by promoting inflammation, which may be related to the regulation of miR-1908-5p expression and the STAT3 signaling pathway. These results suggest that the regulation of HOTTIP may be a promising therapeutic strategy for RA. | |
| 33130920 | Impact of COVID-19 pandemic on rheumatoid arthritis from a Multi-Centre patient-reported q | 2021 Feb | During the coronavirus disease-2019 (COVID-19) pandemic there were several barriers to treatment access and medication adherence in rheumatoid arthritis (RA) patients. There is no information regarding the RA patient health status in Egypt during the COVID-19. Thus,the aim of this work was to study the impact of the pandemic on RA patients through a patient-reported questionnaire and to determine the influence of gender, geographic regions. This multi-centre study initiated by the Egyptian College of Rheumatology (ECR) was conducted on 1037 RA patients attending rheumatology clinics from 10 governorates. The questionnaire provided covered socio-demographic data, health/disease status, information/knowledge about COVID-19 and medical/family history of the infection. Patients mean age was 44.2 ± 12.3 years;855 females and 182 males; 539(52%) from rural and 497(48%) from urban areas. 41.8% reported a striking difficulty to obtain hydroxychloroquine during the pandemic. The majority (70%) considered maintaining a regular visit to the rheumatologist in addition to remote contact mainly by phone (44.4%) or via WhatsApp (33.1%), in particular among male and urban patients. Urban patients were more likely to be infected by COVID-19 (12.9% vs 6.2%; p < 0.0001) than rural. Northern cities had more patients with suspected COVID-19 (13.9% vs 6.1%; p < 0.0001); was significantly associated with more disease flares (30.8% vs 5.8%) with subsequent change in the RA treatment (20.9% vs 6.4%; p < 0.0001). Patients with RA faced remarkable difficulty to obtain their medications with subsequent change in their disease status. The challenges of the pandemic have hastened changes in the way we deliver health care. |