Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
33788436 [Differential metabolites and metabolic pathways involving acupuncture-induced improvement 2021 Feb 25 OBJECTIVE: To analyze the endogenous metabolic biomarkers and pathways in serum involving acupuncture-induced improvement of symptoms of patients with rheumatoid arthritis (RA) by using metabolomics technique. METHODS: A total of 30 RA patients who were treated in the Department of Acupuncture and Moxibustion of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine (from January 2018 to October 2018) were selected in the present study. They were randomly and equally divided into acupuncture group and medication group. Acupuncture (lifting-thrusting reinforcing and uniform reducing-reinforcing methods) was applied to bilateral Fengchi (GB20), Yangchi (TE4), Quchi (LI11), Yingu (KI10), Taixi (KI3), Xuehai （SP10）, Guanyuan (CV4), Yanglingquan (GB34) and Ashi-points for 20 min every time, once daily for 3 months. Patients of the medication group were asked to take Tripterygium Wilfordii Polyglycoside tablets (a positive drug for RA, one tablet per time, 3 times a day) for 3 months. Other 10 healthy volunteers were selected as the normal control group. The tenderness scale (0-4 points) and swelling scale (0-3 points) and morning stiffness time were recorded, and serum rheumatoid factor (RF), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were detected for analyzing pharmacodynamic effects. Serum samples were captured for profiling and quantifying metabolite biomarkers by using GC-MS (gas chromatography-mass spectrometry) technique. The acquired metabolite profiles were processed (multivariable data analysis) by using ProteoWizard package, XCMS Online software and SIMCA 13.0 software, respectively, followed by screening differential metabolites according to variable importance projection (VIP) and by constructing metabolic pathways with MetaboAnalyst 4.0. RESULTS: After acupuncture treatment, the tenderness score, swelling score, morning stiffness time, serum RF and CRP contents were significantly decreased in both acupuncture and medication groups in comparison with their own pretreatment (P<0.05). No significant differences were found between acupuncture and medication groups in the levels of tenderness score, swelling score, morning stiffness time, serum RF and CRP contents (P>0.05). A total of 14 differential metabolites including citrate, creatine, 3-hydroxybutyrate arachidonic acid, arachidonic acid, valine, lactic acid and palmitic acid (up-regulated), and tryptophan, arginine, L-phenylalanine, glucose, glycine, glutamine, aspartic acid and (down-regulated) which mainly involve metabolic pathways of alanine, aspartic acid and glutamate; metabolism of phenylalanine, tyrosine and tryptophan; metabolism of glycine, serine and threonine; glyoxalic acid dicarboxylic acid metabolism; metabolism of starch and sucrose; and metabolism of phenylalanine and arachidonic acid, respectively.Citrate, creatine, arachidonic acid, valine and glucose was positively correlated with tenderness index, swelling index, morning stiff time, RF, CRF and ESR. Glycine, L-phenylalanine , glutamine was negatively correlated with efficacy indicators. CONCLUSION: Acupuncture can relieve symptoms of patients with RA, which may be related to its effects in improving amino acid metabolism and glucose metabolism.
34049858 Glucocorticoid discontinuation in patients with early rheumatoid and undifferentiated arth 2021 Sep OBJECTIVES: To evaluate the success rate of glucocorticoid discontinuation and to study which factors are associated with successful discontinuation. METHODS: Data from two treat-to-target studies, BeSt (target Disease Activity Score (DAS) ≤2.4) and IMPROVED (target DAS <1.6), were evaluated for all patients initially treated with a tapered high dose of prednisone with conventional synthetic disease-modifying antirheumatic drugs. Prednisone was discontinued when DAS ≤2.4 was maintained for 28 weeks in BeSt and as soon as DAS was <1.6 in IMPROVED. Discontinuation was considered successful if the target was maintained at the next visit. Logistic regression analyses were performed to identify predictors of successful discontinuation. A mixed effects logistic regression model was used to assess whether primary versus secondary discontinuation was as successful. RESULTS: In the BeSt study, 40% (47 of 93) of patients flared after primary prednisone discontinuation, and of the other 60% (56 of 93), 38% had to restart later. Of those who restarted (secondary discontinuation), 47% (17 of 35) again flared. In IMPROVED, after primary discontinuation 39% (158 of 400) flared, and of the other 61% (242 of 400), 40% had to restart later. After secondary discontinuation 49% (68 of 139) flared. Only in IMPROVED a secondary attempt was less successful (BeSt OR 0.71, p=0.45; IMPROVED OR 0.60, p=0.01). A lower DAS both at baseline and stop visit and male gender (in IMPROVED) were associated with successful primary discontinuation. CONCLUSION: Primary glucocorticoid discontinuation resulted in direct loss of disease control in approximately 40% and secondary in 50% of patients. 'Standard' baseline characteristics seem insufficient to personalise the duration of temporary glucocorticoid bridging, but the DAS at the time of discontinuation might provide guidance.
33820895 Portuguese multidisciplinary recommendations for non-pharmacological and non-surgical inte 2021 Jan BACKGROUND: Patients with rheumatoid arthritis (RA) report significant levels of disease impact, which are improved, but not fully abrogated by immunosuppressive therapy, even when remission is achieved. This imposes the need for adjuvant interventions targeting the uncontrolled domains of disease impact. Non-pharmacological interventions are widely used for this purpose, but they have not been the object of professional recommendations or guidelines. OBJECTIVE: To propose multidisciplinary recommendations to inform clinical care providers regarding the employment of non-pharmacological and non-surgical interventions in the management of patients with RA. METHODS: The EULAR standardized operating procedures for the development of recommendations were followed. First, a systematic literature review was performed. Then, a multidisciplinary Technical Expert Panel (TEP) met to develop and discuss the recommendations and research agenda. For each developed recommendation i) the level of evidence and grade of recommendation were determined, and ii) the level of agreement among TEP members was set. A recommendation was adopted if approved by ≥75% of the TEP members, and the level of agreement was considered high when ≥8. All relevant national societies were included in this construction process to attain their endorsement. RESULTS: Based on evidence and expert opinion, the TEP developed and agreed on five overarching principles and 12 recommendations for non-pharmacological and non-surgical interventions in patients with RA. The mean level of agreement between the TEP members ranged between 8.5 and 9.9. The recommendations include a broad spectrum of intervention areas, such as exercise, hydrokinesiotherapy, psychological interventions, orthoses, education, general management of comorbidities, among others; and they set the requirements for their application. CONCLUSIONS: These recommendations are based on the consensus judgment of clinical experts from a wide range of disciplines and patients' representatives from Portugal. Given the evidence for effectiveness, feasibility and safety, non-pharmacological and non-surgical interventions should be an integral part of standard care for people with RA. It is hoped that these recommendations should be widely implemented in clinical practice. The target audience for these recommendations includes all health professionals involved in the care of patients with RA. The target patient population includes adult Portuguese people with RA.
33559176 Stratification of methotrexate-induced oral ulcers in rheumatoid arthritis patients. 2021 May AIM: There is a deficiency in the data concerning the clinical forms of methotrexate-induced oral ulcers. This study was conducted to stratify clinical forms of methotrexate-induced oral ulcers in rheumatoid arthritis patients. METHODS: This study included rheumatoid arthritis patients receiving methotrexate as monotherapy. All eligible patients were subjected to thorough clinical examination and full history to identify oral events. Drug history, dose, and duration of MTX were recorded. RESULTS: Among 794 rheumatoid arthritis patients, mean methotrexate dose and duration were 14.3 mg/week and 5.2 years, respectively. Oral ulcers were detected in 6.2% of the patients and 30% of the patients reported previous oral ulcers. Among the detected oral ulcers, 44.9% manifested as deep irregular ulcers, 30.6% presented as aphthous-like ulcers, 14.3% were diffuse mucositis, and 10.2% appeared as lichenoid reaction. CONCLUSION: Methotrexate-induced oral ulceration could be localized or generalized. Localized forms were more noticed than generalized forms. Higher doses and longer durations of methotrexate were detected among patients with generalized oral ulcers.
33933845 Associations of serum cytokines and chemokines with the risk of incident cancer in a prosp 2021 Aug OBJECTIVES: We aimed to assess whether serum cytokine/chemokine concentrations predict incident cancer in RA patients. METHODS: Data from cancer-free enrollees in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry were linked to a national VA oncology database and the National Death Index (NDI) to identify incident cancers. Seventeen serum cytokines/chemokines were measured from enrollment serum and an overall weighted cytokine/chemokine score (CK score) was calculated. Associations of cytokines/chemokines with all-site, lung, and lymphoproliferative cancers were assessed in Cox regression models accounting for relevant covariates including age, sex, RA disease activity, and smoking. RESULTS: In 1216 patients, 146 incident cancers (42 lung and 23 lymphoproliferative cancers) occurred over 10,072 patient-years of follow-up with a median time of 4.6 years from enrollment (cytokine/chemokine measurement) to cancer incidence. In fully adjusted models, CK score was associated with a higher risk of all-site (aHR 1.32, 95% CI 1.01-1.71, p < 0.001), lung (aHR 1.81, 1.40-2.34, p = 0.001), and lung/lymphoproliferative (aHR 1.54 [1.35-1.75], p < 0.001) cancer. The highest quartile of CK score was associated with a higher risk of all-site (aHR 1.91, 0.96-3.81, p = 0.07; p-trend = 0.005), lung (aHR 8.18, 1.63-41.23, p = 0.01; p-trend < 0.001), and lung/lymphoproliferative (aHR 4.56 [1.84-11.31], p = 0.001; p-trend < 0.001) cancer. Thirteen of 17 individual analytes were associated with incident cancer risk. CONCLUSION: Elevated cytokine/chemokine concentrations are predictive of future cancer in RA patients, particularly lung and lymphoproliferative cancers. These results suggest that the measurement of circulating cytokines/chemokines could be informative in cancer risk stratification and could provide insight into future cancer prevention strategies in RA, and possibly individuals without RA.
34492036 Pentosan polysulfate sodium prevents functional decline in chikungunya infected mice by mo 2021 Chikungunya virus (CHIKV) is an arthropod-borne virus that causes large outbreaks world-wide leaving millions of people with severe and debilitating arthritis. Interestingly, clinical presentation of CHIKV arthritides have many overlapping features with rheumatoid arthritis including cellular and cytokine pathways that lead to disease development and progression. Currently, there are no specific treatments or vaccines available to treat CHIKV infections therefore advocating the need for the development of novel therapeutic strategies to treat CHIKV rheumatic disease. Herein, we provide an in-depth analysis of an efficacious new treatment for CHIKV arthritis with a semi-synthetic sulphated polysaccharide, Pentosan Polysulfate Sodium (PPS). Mice treated with PPS showed significant functional improvement as measured by grip strength and a reduction in hind limb foot swelling. Histological analysis of the affected joint showed local inflammation was reduced as seen by a decreased number of infiltrating immune cells. Additionally, joint cartilage was protected as demonstrated by increased proteoglycan staining. Using a multiplex-immunoassay system, we also showed that at peak disease, PPS treatment led to a systemic reduction of the chemokines CXCL1, CCL2 (MCP-1), CCL7 (MCP-3) and CCL12 (MCP-5) which may be associated with the reduction in cellular infiltrates. Further characterisation of the local effect of PPS in its action to reduce joint and muscle inflammation was performed using NanoStringâ„¢ technology. Results showed that PPS altered the local expression of key functional genes characterised for their involvement in growth factor signalling and lymphocyte activation. Overall, this study shows that PPS is a promising treatment for alphaviral arthritis by reducing inflammation and protecting joint integrity.
34432649 A comprehensive transcriptomic analysis of alternate interferon signaling pathways in peri 2021 Aug 25 Interferon (IFN) signaling pathways play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Prior studies have mainly studied mixed alterations in the IFN signaling pathway in RA, but these studies have not been sufficient to elucidate how imbalanced IFN signaling subtly influences immune cells. Single-cell RNA (scRNA) sequencing makes it possible to better understand the alternations in the interferon signaling pathways in RA. In the present study, we found that IFN signaling pathways were activated in natural killer (NK) cells, monocytes, T cells, B cells, and most immune cell subclasses in RA. We then explored and analyzed the connections between abnormal IFN signaling pathways and cellular functional changes in RA. Single-Cell rEgulatory Network Inference and Clustering (SCENIC) analysis and gene regulatory network (GRN) construction were also performed to identify key transcription factors in RA. Finally, we also investigated altered IFN signaling pathways in multiple RA peripheral blood samples, which indicated that abnormal IFN signaling pathways were universally observed in RA. Our study contributes to a better understanding of the delicate and precise regulation of IFN signaling in the immune system in RA. Furthermore, common alternations in IFN signaling pathway-related transcription factors could help to identify novel therapeutic targets for RA treatment.
33547838 JNK pathway-associated phosphatase associates with rheumatoid arthritis risk, disease acti 2021 Apr BACKGROUND: This study aimed to investigate the relationship of serum JNK pathway-associated phosphatase (JKAP) expression with rheumatoid arthritis (RA) risk and clinical features, also to explore the longitudinal change of JKAP during etanercept treatment and its relationship with etanercept treatment response in RA patients. METHODS: A total of 87 RA patients and 44 healthy controls (HCs) were enrolled; then, their JKAP expression in serum was determined by enzyme-linked immunosorbent assay (ELISA). Among 87 RA patients, 42 cases further received the 24-week etanercept treatment; then, their JKAP level in serum (detected by ELISA) and clinical response (evaluated by disease activity score in 28 joints (DAS28) score) were evaluated at week 4 (W4), week 12 (W12), and week 24 (W24) after initiation of etanercept treatment. RESULTS: JKAP expression was decreased in RA patients compared to HCs, which disclosed a good predictive value for RA risk. JKAP expression was negatively associated with tender joint count, swollen joint count, erythrocyte sedimentation rate, C-reactive protein, and DAS28 in RA patients, respectively. For RA patients who received 24-week etanercept treatment, their clinical response rate was 0.0%, 33.3%, 50.0%, and 69% at W0, W4, W12, and W24, respectively. Importantly, JKAP was gradually increased during etanercept treatment, whose longitudinal elevation positively related to etanercept treatment response in RA patients. CONCLUSION: Circulating JKAP links with decreased RA risk and mild disease activity, whose longitudinal elevation positively relates to etanercept treatment response.
34528855 How effective are JAK-inhibitors? Perspectives from clinical trials and real-world studies 2022 Mar INTRODUCTION: JAK-inhibitors have emerged as a new treatment option for rheumatoid arthritis, with five molecules currently available in different parts of the world: tofacitinib, baricitinib, upadacitinib, peficitinib, and filgotinib. These molecules have been the subject of numerous trials looking at their efficacy (how well they perform in controlled conditions) but also some observational studies from the general population to assess their effectiveness (how well treatment perform under real conditions). With each their own weaknesses and strengths, they give different but complementary information. AREAS COVERED: We will review what we can learn from trials and real-world studies on how effective JAK-inhibitors are in the treatment of rheumatoid arthritis. EXPERT OPINION: Trials of JAK-inhibitors have shown that JAK-inhibitors are efficacious for the treatment of rheumatoid arthritis. However, their main outcomes are not clinically meaningful as their aim is mainly the regulatory authorization of the product. Real-world studies are important as they evaluate the real-life effectiveness of the compounds, however, they are scarce at the moment, mainly evaluating tofacitinib and of variable quality. Future high-quality studies are needed to assess the real-world effectiveness of JAK-inhibitors in a more complete manner.
33430948 Risk of opportunistic infections in patients with rheumatoid arthritis initiating abatacep 2021 Jan 11 BACKGROUND: To evaluate incidence of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with abatacept in clinical trials. METHODS: This pooled analysis of 16 randomized, double-blind/open-label trials, with ≥ 1 abatacept (intravenous or subcutaneous) arm, and with/without placebo control covered cumulative (controlled short-term and open-label long-term) abatacept exposure periods. OIs were analyzed separately in controlled (abatacept and placebo individually) and cumulative periods. OIs were identified using a prespecified list; events were independently adjudicated. Unadjusted incidence rates (IRs; per 100 patient-years) with 95% confidence intervals (CIs) were calculated. RESULTS: In cumulative periods, 7044 patients received abatacept, with a mean (standard deviation) duration of exposure of 36.9 (26.2) months (21,274 patient-years of exposure). IRs (95% CIs) of OIs were 0.17 (0.05-0.43) for abatacept and 0.56 (0.22-1.15) for placebo during the controlled periods and 0.21 (0.15-0.28) for abatacept during the cumulative periods. There was 1 case of tuberculosis in both the abatacept (IR [95% CI] 0.04 [0.00-0.24]) and placebo (IR [95% CI] 0.08 [0.00-0.44]) groups during the controlled periods; 13 verified tuberculosis cases (IR [95% CI] 0.06 [0.03-0.10]) were reported in the cumulative period. Herpes zoster was reported numerically more often with abatacept (IR 1.9 [1.4-2.5]), versus placebo (1.7 [1.1-2.6]) in the controlled periods; within the cumulative period, herpes zoster IR (95% CI) was 1.53 (1.36-1.71) for abatacept-treated patients. CONCLUSION: In controlled periods of the clinical trials, abatacept-treated patients had similarly low rates of OIs compared with placebo-treated patients. Overall, OI rates were similar among abatacept-treated patients in the controlled and cumulative periods and consistent with the ranges reported in the literature.
33493980 TLR expression profiles are a function of disease status in rheumatoid arthritis and exper 2021 Mar The role of the innate immune system has been established in the initiation and perpetuation of inflammatory disease, but less attention has been paid to its role in the resolution of inflammation and return to homeostasis. Toll-like receptor (TLR) expression profiles were analysed in tissues with differing disease status in rheumatoid arthritis (RA), ankylosing spondylitis (AS), and in experimental arthritis. TLR gene expression was measured in whole blood and monocytes, before and after TNF blockade. In RA and osteoarthritis synovia, the expression of TLRs was quantified by standard curve qPCR. In addition, four distinct stages of disease were defined and validated in collagen-induced arthritis (CIA), the gold standard animal model for RA - pre-onset, early disease, late disease and immunised mice that were resistant to the development of disease. TLR expression was measured in spleens, lymph nodes, blood cells, liver and the paws (inflamed and unaffected). In RA whole blood, the expression of TLR1, 4 and 6 was significantly reduced by TNF blockade but the differences in TLR expression profiles between responders and non-responders were less pronounced than the differences between RA and AS patients. In RA non-responders, monocytes had greater TLR2 expression prior to therapy compared to responders. The expression of TLR1, 2, 4 and 8 was higher in RA synovium compared to control OA synovium. Circulating cytokine levels in CIA resistant mice were similar to naïve mice, but anti-collagen antibodies were similar to arthritic mice. Distinct profiles of inflammatory gene expression were mapped in paws and organs with differing disease status. TLR expression in arthritic paws tended to be similar in early and late disease, with TLR1 and 2 moderately higher in late disease. TLR expression in unaffected paws varied according to gene and disease status but was generally lower in resistant paws. Disease status-specific profiles of TLR expression were observed in spleens, lymph nodes, blood cells and the liver. Notably, TLR2 expression rose then fell in the transition from naïve to pre-onset to early arthritis. TLR gene expression profiles are strongly associated with disease status. In particular, increased expression in the blood precedes clinical manifestation.
31895110 Anti-Jo-1 Syndrome Often Misdiagnosed as Rheumatoid Arthritis (for Many Years): A Single-C 2021 Jun 1 BACKGROUND: Antisynthetase syndrome is characterized by a triad of myositis, arthritis, and interstitial lung disease. Anti-Jo-1 is the most common associated autoantibody. This study planned to look at the presentation of anti-Jo-1 antisynthetase syndrome in a single Indian center. METHODS AND MATERIALS: This was a medical records review single-center study that included patients with anti-Jo-1 antisynthetase syndrome over 10 years. RESULTS: This study included 27 patients with anti-Jo-1 antisynthetase syndrome, with mean age of 40 ± 9.2 years and female preponderance (female-to-male ratio, 4:1). At presentation, the characteristic triad was present in only 4 patients. A majority presented with the incomplete form, with 2 clinical features (of triad) in 11 and single feature (of triad) being present in 12 patients at initial presentation. Seven presented only with polyarthritis, out of which 6 had been earlier diagnosed as rheumatoid arthritis. Time gap from diagnosis of "rheumatoid arthritis" to antisynthetase syndrome ranged from 3 to 20 years. In patients who had only arthritis in the beginning, there was a significantly longer delay to diagnosis of antisynthetase syndrome, higher frequency of rheumatoid factor, and lower frequency of anti-Ro-52. Overall, outcome was good, with Eastern Cooperative Oncology Group class 1 or 2 in most except 2 patients. CONCLUSIONS: Anti-Jo-1 antisynthetase syndrome commonly presented as incomplete (not a triad) and often only with arthritis. These patients are diagnosed and treated as rheumatoid arthritis for many years, before a diagnosis of antisynthetase syndrome is made. Being aware of this presentation may help in earlier diagnosis by actively searching for subtle clues.
34918712 Identifying the hub genes and immune infiltration related to pyroptosis in rheumatoid arth 2021 Dec 17 Rheumatoid arthritis (RA) is one of the most common autoimmune joint disorders globally, but its pathophysiological mechanisms have not been thoroughly investigated. Pyroptosis significantly correlates with programmed cell death. However, targeting pyroptosis has not been considered as a therapeutic strategy in RA due to a lack of systematic studies on validated biomarkers. The present study aimed to identify hub pyroptosis biomarkers and immune infiltration in RA. The gene expression profiles of synovial tissues were obtained from the Gene Expression Omnibus (GEO) database to identify differentially expressed pyroptosis genes (DEPGs). Meanwhile, the CIBERSORT algorithm was used to explore the association between immune infiltration and RA. Consequently, two hub DEPGs (EGFR and JUN) were identified as critical genes in RA. Through gene ontology and pathway enrichment analysis. EGFR and JUN were found to be primarily involved in the ErbB signaling pathway, PD-1 checkpoint pathway, GnRH signaling pathway, etc. Furthermore, for immune infiltration analysis, the pyroptosis genes EGFR and JUN were closely connected with four and one immune cell types, respectively. Overall, this study presents a novel method to identify hub DEPGs and their correlation with immune infiltration, which may provide novel perspectives into the diagnosis and treatment of patients with RA.
34461491 The impact of airborne endotoxin exposure on rheumatoid arthritis-related joint damage, au 2021 Nov Airborne biohazards are risk factors in the development and severity of rheumatoid arthritis (RA) and RA-associated lung disease, yet the mechanisms explaining this relationship remain unclear. Lipopolysaccharide (LPS, endotoxin) is a ubiquitous inflammatory agent in numerous environmental and occupational air pollutant settings recognized to induce airway inflammation. Combining repetitive LPS inhalation exposures with the collagen induced arthritis (CIA) model, DBA1/J mice were assigned to either: sham (saline injection/saline inhalation), CIA (CIA/saline), LPS (saline/LPS 100 ng inhalation), or CIA + LPS for 5 weeks. Serum anti-citrullinated (CIT) protein antibody (ACPA) and anti-malondialdehyde-acetaldehyde (MAA) antibodies were strikingly potentiated with co-exposure (CIA + LPS). CIT- and MAA-modified lung proteins were increased with co-exposure and co-localized across treatment groups. Inhaled LPS exacerbated arthritis with CIA + LPS > LPS > CIA versus sham. Periarticular bone loss was demonstrated in CIA and CIA + LPS but not in LPS alone. LPS induced airway inflammation and neutrophil infiltrates were reduced with co-exposure (CIA + LPS). Potentially signaling transition to pro-fibrotic processes, there were increased infiltrates of activated CD11c(+)CD11b(+) macrophages and transitioning CD11c(+)CD11b(int) monocyte-macrophage populations with CIA + LPS. Moreover, several lung remodeling proteins including fibronectin and matrix metalloproteinases as well as complement C5a were potentiated with CIA + LPS compared to other treatment groups. IL-33 concentrations in lung homogenates were enhanced with CIA + LPS with IL-33 lung staining driven by LPS. IL-33 expression was also significantly increased in lung tissues from patients with RA-associated lung disease (N = 8) versus controls (N = 7). These findings suggest that patients with RA may be more susceptible to developing interstitial lung disease following airborne biohazard exposures enriched in LPS.
35003068 Toward Overcoming Treatment Failure in Rheumatoid Arthritis. 2021 Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation and bone erosion. The exact mechanism of RA is still unknown, but various immune cytokines, signaling pathways and effector cells are involved. Disease-modifying antirheumatic drugs (DMARDs) are commonly used in RA treatment and classified into different categories. Nevertheless, RA treatment is based on a "trial-and-error" approach, and a substantial proportion of patients show failed therapy for each DMARD. Over the past decades, great efforts have been made to overcome treatment failure, including identification of biomarkers, exploration of the reasons for loss of efficacy, development of sequential or combinational DMARDs strategies and approval of new DMARDs. Here, we summarize these efforts, which would provide valuable insights for accurate RA clinical medication. While gratifying, researchers realize that these efforts are still far from enough to recommend specific DMARDs for individual patients. Precision medicine is an emerging medical model that proposes a highly individualized and tailored approach for disease management. In this review, we also discuss the potential of precision medicine for overcoming RA treatment failure, with the introduction of various cutting-edge technologies and big data.
33512320 Use of eHealth by Patients With Rheumatoid Arthritis: Observational, Cross-sectional, Mult 2021 Jan 29 BACKGROUND: The use of eHealth tools (eg, the internet, mobile apps, and connected devices) in the management of chronic diseases and for rheumatoid arthritis is growing. eHealth may improve the overall quality of care provided to patients with chronic diseases. OBJECTIVE: The primary objective of this study was to describe eHealth use by patients with rheumatoid arthritis in France. The secondary objectives were to identify associations between patient demographics and disease characteristics and the use of eHealth tools, and assess their expectations of eHealth. METHODS: In this cross-sectional, multicenter study, patients with rheumatoid arthritis, according to the 2010 ACR/EULAR classification criteria, were recruited from 5 university hospitals (Bordeaux, Clermont-Ferrand, Limoges, Montpellier, and Toulouse). Patients completed an anonymous self-questionnaire, including demographic data, evaluating their eHealth use (ie, access, support, frequency of use, type of use, and reason for use). The rheumatologist in charge of each patient completed an independent medical questionnaire on disease characteristics, activity of rheumatoid arthritis, and treatments. Data were collected between December 2018 and July 2019. RESULTS: Questionnaires were completed by 575 participants, with a mean age of 62 (SD 13) years, 447 (77.7%) of whom were female. Overall, 82.2% (473/575) of the participants had access to eHealth through a computer (402/467, 86.1%), tablet (188/467, 40.2%), or smartphone (221/467, 47.3%). Of these, 36.4% (170/467) of the participants used the internet for health in general, and 28.7% (134/467) used it specifically for rheumatoid arthritis-related reasons. All these 134 patients used eHealth to learn about disease pathology, and 66.4% (89/134) of them used it as a tool to help monitor rheumatoid arthritis. Most patients (87/125, 69.6%) had a paper file, 19.2% (24/125) used a digital tool (spreadsheets, 10/125, 8%; mobile app, 9/125, 7.2%; or website, 5/125, 4%), and 24.8% (31/125) did not use any tools for monitoring. Few patients (16/125, 12.8%) used tools for treatment reminders. About 21.6% (27/125) of the patients using eHealth used a specific app for rheumatoid arthritis. Univariate analysis showed that age, education level, employment status, treatment, comorbidities, membership of a patient association, and patient education program were associated with eHealth use for rheumatoid arthritis. Multivariate analysis showed that membership of a patient association (odds ratio [OR] 5.8, 95% CI 3.0-11.2), use of biologic disease-modifying antirheumatic drugs (OR 0.6, 95% CI 0.4-1.0), and comorbidities (OR 0.7, 95% CI 0.6-0.8) remained associated with eHealth use for rheumatoid arthritis. Recommendation by a doctor (225/330, 68.2%), ease of use (105/330, 31.8%), and data security (69/330, 20.9%) were factors favoring the use of eHealth. CONCLUSIONS: To date, few patients have used eHealth for disease management. The use of a reliable and validated eHealth tool for rheumatoid arthritis could therefore be promoted by rheumatologists and could optimize therapeutic adherence.
34879087 Effects of different doses of complete Freund's adjuvant on nociceptive behaviour and infl 2021 Complete Freund's adjuvant (CFA) has been used to develop the arthritic or inflammatory condition in the animal, but there is a lack of information concerning high CFA doses on nociceptive behaviour and inflammatory parameters. This study aimed to compare the effects of different high doses of CFA in rat to closely mimic nociceptive and inflammatory parameters of rheumatoid arthritis (RA) in humans. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6): Control (C), CFA-induced polyarthritic groups at 5.0 mg/mL (CFA 5.0), 7.5 mg/mL (CFA 7.5) and 10.0mg/mL (CFA 10.0). The rats' right hindpaw was inoculated with CFA intradermally and developed into a polyarthritic state within 20 days. Nociceptive behavioural assessments, including von Frey and hot plate tests and spontaneous activities, were conducted on day 0, 7, 15 and 20. Bilateral ankle joints diameter and circumference, full blood count, joints and paw histological examinations were also conducted throughout the study period. Based on the results, CFA 5.0 and CFA 7.5 groups showed a significant increase in spontaneous activities and development of thermal hyperalgesia but no change in body weight and food intake, no development of tactile allodynia and haematological indices, and no significant morphological changes of joints histology. Meanwhile, CFA 10.0 group demonstrated significant and constant changes in all nociceptive and inflammatory parameters investigated. In conclusion, CFA at the dose of 10mg/mL has the most potential and reliable dosage to develop polyarthritis in a rat model to mimic RA condition in humans.
33241299 Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: clinical 2021 May 14 OBJECTIVES: RA-associated interstitial lung disease (RA-ILD) is commonly associated with acute exacerbations (ILD-AE). This study examined the clinical characteristics and risk factors of ILD-AE and mortality of RA-ILD. METHODS: We retrospectively collected data on 165 RA-ILD patients who visited or were admitted to our hospital between January 2007 and December 2019. We compared the clinical characteristics of patients who did and did not develop ILD-AE and identified variables significantly associated with ILD-AE. We also compared the admission characteristics of those who survived and those who died after admission for ILD-AE. ILD-AE was defined using previously proposed criteria, modified slightly for application to RA-ILD. RESULTS: The mean patient age was 73.6 years (s.d. 9.7) and 97 (71.9%) patients were female. Thirty (22.2%) patients developed ILD-AE, 13 (43.3%) of whom died. In univariate analyses, neither the usual interstitial pneumonia (UIP) pattern nor MTX was associated with ILD-AE. In multivariate analyses, the UIP pattern was significantly associated with ILD-AE [odds ratio (OR) 2.55 (95% CI 1.05, 6.20), P = 0.038]. In the Cox proportional hazards model, the UIP pattern [hazard ratio (HR) 4.67 (95% CI 1.02, 21.45), P = 0.048] was significantly associated with death, while MTX use [HR 0.16 (95% CI 0.04, 0.72), P = 0.016] was significantly associated with survival. CONCLUSION: Our data suggest that the UIP pattern is related to ILD-AE. Furthermore, both the UIP pattern and non-use of MTX might be related to death from ILD-AE in RA-ILD.
32757870 Healing of erosions in rheumatoid arthritis remains elusive: results with 24 months of the 2021 Jan Objective: Erosion healing in rheumatoid arthritis (RA) is difficult to demonstrate. This extension study aimed to determine whether 2 years of teriparatide (TPTD) produces erosion healing. Method: Subjects in a previous 12 month randomized controlled trial of TPTD in RA were invited to receive 12 additional months of open-label TPTD. Eleven of the 24 original subjects were enrolled in the extension study, six of whom received TPTD in the final 12 months only. Subjects receiving 24 months of TPTD were assessed for reduction in erosion volume from baseline using computed tomography. We also compared erosion volumes between 12 and 24 months of TPTD. Large erosions in subjects receiving TPTD for 24 months were examined for volume change. Results: In the six patients who received 24 months of TPTD, there was no significant change in erosion volume at the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints compared with baseline. The six subjects who received 24 months of TPTD had similar changes in erosion volume to the five who received 12 months of TPTD, in MCP (p = 0.17) and PIP (p = 0.63) joints. Assessment of large erosions in those receiving TPTD for 24 months showed no evidence of erosion healing. Conclusion: While this extension study was too small to be conclusive, we observed no evidence of reduction in erosion volume with the addition of TPTD for 24 months in subjects with RA in whom disease activity was controlled on a tumour necrosis factor inhibitor. This is consistent with our negative findings at 12 months.
34622769 Comparative efficacy and safety of etanercept biosimilars in comparison with etanercept in 2021 Dec OBJECTIVE: We aimed to assess the relative efficacy and safety of etanercept biosimilars and etanercept originators in patients with active rheumatoid arthritis (RA) who showed an inadequate response to methotrexate (MTX). MATERIALS AND METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of etanercept biosimilars vs. etanercept originators in patients with active RA despite treatment with MTX. RESULTS: Three RCTs involving 1,200 patients, including 4 types of biologics, were included. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that LBEC0101 had a high probability of being the better treatment in terms of the American College of Rheumatology 20 (ACR20) response rate (SUCRA = 0.744), followed by HD203 (SUCRA = 0.457), SB4 (SUCRA = 0.446), and etanercept (SUCRA = 0.352), although no difference in the ACR20 response rate between the biosimilars and etanercept groups was found. Although not statistically significant, there was a difference in the ranking probability of safety based on serious adverse events (SAEs) among interventions. Ranking probability based on SUCRA values indicated that LBEC0101 had the highest probability of being the safest treatment (SUCRA = 0.638), followed by SB4 (SUCRA = 0.495) and HD203 (SUCRA = 0.475), while etanercept had the lowest probability of being the safest treatment (SUCRA = 0.393). CONCLUSION: No significant difference was found between etanercept biosimilars and etanercept originators in patients with active RA despite treatment with MTX in terms of the ACR20 response rate and SAEs.