Browse

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

ID PMID Title PublicationDate abstract
34867956 Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling o 2021 The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from the fecal samples of 93 RA patients and 16 healthy subjects. Microbiota profiling was conducted through 16S rRNA sequencing and bioinformatics analyses. The effects of Bifidobacterium strains on human peripheral blood mononuclear cells and collagen-induced arthritis (CIA) mice were assessed. Significant differences in gut microbiota composition were observed in patients with different RF levels. The relative abundance of Bifidobacterium and Collinsella was lower in RF-high than in RF-low and RF-negative RA patients, while the relative abundance of Clostridium of Ruminococcaceae family was higher in RF-high than in RF-low and RF-negative patients. Among 10 differentially abundant Bifidobacterium, B. longum RAPO exhibited the strongest ability to inhibit IL-17 secretion. Oral administration of B. longum RAPO in CIA mice, obese CIA, and humanized avatar model significantly reduced RA incidence, arthritis score, inflammation, bone damage, cartilage damage, Th17 cells, and inflammatory cytokine secretion. Additionally, B. longum RAPO significantly inhibited Th17 cells and Th17-related genes-IL-17A, IRF4, RORC, IL-21, and IL-23R-in the PBMCs of rheumatoid arthritis patients. Our findings suggest that B. longum RAPO may alleviate RA by inhibiting the production of IL-17 and other proinflammatory mediators. The safety and efficacy of B. longum RAPO in patients with RA and other autoimmune disorders merit further investigation.
34529319 LncRNA SNHG14 contributes to proinflammatory cytokine production in rheumatoid arthritis v 2021 Dec Rheumatoid arthritis (RA) is a widespread autoimmune disorder of the joints. Long noncoding RNAs (lncRNAs) have been reported to participate in the pathogenesis of RA by serving as competitive endogenous RNAs. LncRNA small nucleolar RNA host gene 14 (SNHG14) is involved in the development of various diseases. Here, we found that high expression of SNHG14 in RA was closely related to the disease activity. Functional assays indicated that SNHG14 knockdown obviously hampered phorbol myristate acetate-activated THP-1 (pTHP-1) cell proliferation and proinflammatory cytokines production. In mechanism, SNHG14 served as a sponge of microRNA-17-5p (miR-17-5p), and misshapen like kinase 1 (MINK1) was a target of miR-17-5p. SNHG14 depletion-induced inhibitory effects on cell proliferation and inflammatory response were reversed by MINK1 overexpression in macrophages. Moreover, SNHG14 promoted the jun N-terminal kinase (JNK) signaling via the miR-17-5p/MINK1 axis. Overall, SNHG14 boosted the process of RA by MINK1 activating the JNK pathway.
34844927 Importance of the second SARS-CoV-2 vaccination dose for achieving serological response in 2022 Mar OBJECTIVES: To assess the kinetics of humoral response after the first and second dose of messenger RNA (mRNA) vaccines in patients with inflammatory joint diseases compared with healthy controls (HC). To analyse factors influencing the quantity of the immune response. METHODS: We enrolled patients with rheumatoid arthritis (RA) and seronegative spondyloarthritis (SpA), excluding those receiving B-cell depleting therapies and assessed the humoral response to mRNA vaccines after the first and the second dose of the vaccine in terms of seroconversion rate and titre. We compared the results to a HC group and analysed the influence of therapies as well as other characteristics on the humoral response. RESULTS: Samples from 53 patients with RA, 46 patients with SpA and 169 healthy participants were analysed. Seroconversion rates after the first immunisation were only 54% in patients with inflammatory arthritis compared with 98% in the HC group. However, seroconversion rates were 100% in all groups after second immunisation. Patients developed reduced antibody titres after the first vaccination compared with HC, but there was no difference after the second dose. While disease modifying anti-rheumatic drug (DMARD) monotherapy did not affect antibody levels, seroconversion rates as well as titre levels were reduced in patients receiving a combination of DMARDs compared with HC. CONCLUSIONS: Patients with inflammatory joint diseases under DMARD therapy show impaired humoral responses to the first vaccine dose but excellent final responses to vaccination with mRNA vaccines. Therefore, the full course of two immunisations is necessary for efficient vaccination responses in patients with inflammatory arthritis under DMARD therapy.
35016462 A narrative review of positive regulation of NLRP3 inflammasome in rheumatoid arthritis. 2021 Dec OBJECTIVE: This paper briefly reviews the pathological characteristics and regulatory mechanism of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and summarizes the relationship between it and rheumatoid arthritis (RA) as a means to improve its therapeutic potential and clinical application. BACKGROUND: RA is a systemic inflammatory disease with a high incidence rate. The early diagnosis and treatment of the disease is difficult, and the current treatment effect of most patients is not significant and accompanied by serious infection risk. Inflammation is an immune protective mechanism in the body. Inflammasome is an intracellular multi-body protein that stimulates the inflammatory response [inducing the release of pro-inflammatory cytokine interleukin (IL)-1β and IL-18] and promotes the death of thermophiles. The NLRP3 inflammatory bodies are assembled from NLRP3, apoptosis-associated speck-like protein (ASC), and pro-caspase-1. Previous studies have enriched our understanding of the activation mechanism of NLRP3 inflammasome, and animal model data suggests that it plays an important role in autoimmune diseases, including RA. METHODS: Literatures about inflammation and RA were extensively reviewed to analyze and discuss. CONCLUSIONS: Especially, we focused on the role of NLRP3 inflammasome in the pathogenesis of RA and the potential of NLRP3 inflammasome or their derivatives in the treatment of RA, which enriched the treatment strategies of inflammatory diseases.
34496051 Risk of Heart Failure in Rheumatoid Arthritis Patients Treated with Tumor Necrosis Factor- 2021 Dec This is a retrospective cohort study by analyzing a multi-institutional electronic medical records database covering 1.3 million individuals (6% of Taiwan's population) to compare the risk of heart failure (HF) in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor-α (TNF-α) inhibitors or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). We included patients with RA aged 20 years and older who had treatment failure with at least 2 different csDMARD regimens and newly switched to another csDMARD regimen or TNFis from 2009 to 2019. We followed patients from initiation of the new therapies to the occurrence of hospitalization for heart failure (hHF), death, to the last clinical visit or December 31, 2020. We performed multivariable Cox proportional hazard models to compare TNF-α inhibitors and csDMARD groups for the risk of hHF, with adjustment for patients' characteristics. A total of 1,278 TNF-α inhibitors and 1,932 csDMARDs treated patients were identified, with 78% being women and having an average age of 55 (SD 13.28) years. The incidence rates of hHF for the TNF-α inhibitors and csDMARD groups were 3.66 and 4.72 per 1,000 person-years, respectively (adjusted hazard ratio (aHR) 0.59; 95% confidence interval (CI) 0.35-0.97), and the results remained consistent in patients both with an HF history (aHR 0.66; 95% CI 0.03-14.46) and without (aHR 0.49; 95% CI, 0.27-0.89). The findings suggest that those who switched to TNF-α inhibitors had a reduced risk of hHF, compared with those who switched to another csDMARD regimen.
34912337 Proteoform Analysis of Matrix Metalloproteinase-9/Gelatinase B and Discovery of Its Citrul 2021 OBJECTIVES: To explore posttranslational modifications (PTMs), including proteolytic activation, multimerization, complex formation and citrullination of gelatinases, in particular of gelatinase B/MMP-9, and to detect in gelatin-Sepharose affinity-purified synovial fluids, the presence of specific MMP proteoforms in relation to arthritis. METHODS: Latent, activated, complexed and truncated gelatinase-A/MMP-2 and gelatinase B/MMP-9 proteoforms were detected with the use of zymography analysis to compare specific levels, with substrate conversion assays, to test net proteolytic activities and by Western blot analysis to decipher truncation variants. Citrullination was detected with enhanced sensitivity, by the use of a new monoclonal antibody against modified citrullines. RESULTS: All MMP-9 and MMP-2 proteoforms were identified in archival synovial fluids with the use of zymography analysis and the levels of MMP-9 versus MMP-2 were studied in various arthritic diseases, including rheumatoid arthritis (RA). Secondly, we resolved misinterpretations of MMP-9 levels versus proteolytic activities. Thirdly, a citrullinated, truncated proteoform of MMP-9 was discovered in archival RA synovial fluid samples and its presence was corroborated as citrullinated hemopexin-less MMP-9 in a small prospective RA sample cohort. CONCLUSION: Synovial fluids from rheumatoid arthritis contain high levels of MMP-9, including its truncated and citrullinated proteoform. The combination of MMP-9 as analyte and its PTM by citrullination could be of clinical interest, especially in the field of arthritic diseases.
34078723 Vascular cell adhesion molecule-1 in rheumatoid arthritis patients: Relation to disease ac 2021 Jun OBJECTIVES: To evaluate the potential role of vascular cell adhesion molecule-1 (VCAM-1), an endothelial factor, in endothelial dysfunction in rheumatoid arthritis (RA) patients, and to determine its relation to disease activity, oxidative stress, and inflammatory markers. METHODS: This study was designed as a cross-sectional case-control study. One-hundred patients with RA were selected from out-patient clinics of Menoufia University Hospital, Menoufia, Egypt from May 2019 to May 2020. Fifty patients previously diagnosed with RA for more than 6 months were included as Group I, and fifty patients newly diagnosed with RA were included as Group II. Fifty healthy age- and gender-matched individuals were evaluated as the control group (Group III). Complete blood count, random blood glucose, erythrocyte sedimentation rate (ESR), lipid profile, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, serum levels of urea, creatinine, C-reactive protein, VCAM-1, malondialdehyde, and total antioxidant capacity were determined. RESULTS: Patients with RA showed significantly higher serum VCAM-1, malondialdehyde, ESR, C-reactive protein, triglycerides, total cholesterol, low-density lipoprotein, and atherogenic index levels than the control group. Also, they showed significantly lower total antioxidant capacity and high-density lipoprotein levels than control group. A significant positive correlation between serum VCAM-1 with disease activity, serum malondialdehyde, ESR, and C-reactive protein was observed. Also, a significant negative correlation between serum VCAM-1 and total antioxidant capacity was present. CONCLUSION: Serum VCAM-1 increases in RA, and it correlates with disease activity, oxidative stress, and inflammatory markers.
33043757 Cost-effectiveness analysis of tofacitinib compared with adalimumab and etanercept in the 2021 Aug BACKGROUND AND OBJECTIVE: This study aimed to evaluate the cost-utility of Tofacitinib (TFC) in patients with severe rheumatoid arthritis (RA) who had not responded well to methotrexate from the Iranian payer's perspective. METHODS: An individual microsimulation Markov model was developed to compare TFC with etanercept (ETN) and Adalimumab (ADA) over a life-time horizon. Treatment efficacy was estimated based on the American College of Rheumatology (ACR) response improvement criteria in 6 months. Changes in the Health Assessment Questionnaire (HAQ) scores were mapped onto utility values to calculate outcomes in terms of QALYs. Direct medical costs were taken from national databases. Uncertainty in model parameters was evaluated by sensitivity analyses. RESULTS: This study demonstrated that TFC was cost-effective in both scenarios. Although TFC was associated with lower QALYs than ETN (6.664 versus 6.876), it was also associated with lower costs over a life-time horizon ($42,565.04 versus $58,696.29). Additionally, TFC was found to be the dominant strategy with a lower cost ($50,299.91 versus $51,550.29) and higher QALYs gained (6.900 versus 6.687) compared to ADA. CONCLUSION: TFC was found to be cost-effective in patients with severe RA who do not respond well to methotrexate compared to ADA, ETN in Iran.
33132219 Circulating Fibroblast Growth Factor-21 Levels in Rheumatoid Arthritis: Associations With 2021 Apr OBJECTIVE: This study evaluated associations between fibroblast growth factor (FGF)-21, an adipokine associated with metabolic stress, and adverse longitudinal changes in body composition and physical functioning in patients with rheumatoid arthritis (RA). METHODS: At baseline and follow-up, patients with RA aged 18-70 years completed whole-body dual-energy X-ray absorptiometry and peripheral quantitative computed tomography to quantify lean mass, fat mass, and muscle density. Dynamometry assessed muscle strength at the hand and knee, and physical functioning was measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). FGF-21 and inflammatory cytokines were measured at baseline. Linear and logistic regression analyses assessed associations between FGF-21 levels and both body composition and physical functioning over time. RESULTS: There were 113 patients with RA enrolled, and 84 (74%) returned for follow-up at a median of 2.68 years. At baseline, FGF-21 was associated with age, smoking, methotrexate use, adiposity, and inflammatory cytokines: tumor necrosis factor receptor type I, YKL-40, vascular endothelial growth factor (VEGF), and resistin. The highest FGF-21 quartile was associated with worse SPPB and HAQ. Higher baseline FGF-21 levels (per 1 SD) were associated with worsening in muscle density and area Z-scores (β -0.06, 95% CI -0.12 to 0.008, P = 0.08; and β -0.05, 95% CI -0.10 to 0.006, P = 0.08, respectively) and a greater probability of a clinically meaningful worsening of HAQ (OR 2.37, 95% CI 1.21-4.64, P = 0.01). The fourth FGF-21 quartile was associated with worsening of SPPB (β -0.57, 95% CI -1.04 to -0.09, P = 0.02). CONCLUSION: FGF-21 levels are associated with obesity and inflammatory cytokines, and with worsening in physical functioning in RA. These data support the hypothesis that FGF-21 can identify patients at risk of functional decline.
33594693 Crossing the barriers: Revisiting the gut feeling in rheumatoid arthritis. 2021 Apr To avoid autoimmunity, it is essential to keep the balance between the defence against pathogens and the maintenance of tolerance to self-antigens. Mucosal inflammation may lead to breakdown of tolerance and activation of autoreactive cells. Growing evidence suggests a major contribution of gut microbiota to the onset of chronic, autoimmune inflammatory diseases including rheumatoid arthritis (RA). RA patients show significant differences in the composition of gut microbiota compared to healthy controls, and in murine arthritis models certain bacteria can induce inflammatory Th17 responses or autoantibody production. The gut microbiota plays an important role in regulating the balance between immunogenic and tolerogenic immune responses. The intestinal barrier is the site of the body where most host-microbiota interaction takes place. Certain microbiota or their metabolites can cause a break in homeostasis by affecting the intestinal barrier integrity and permeability. However, an intact intestinal barrier is essential to separate the intestinal epithelium from toxins, microorganisms, and antigens in the gut lumen. This review will focus on the correlation between a leaky gut and the onset of arthritis. Furthermore, it will be discussed how targeting the intestinal barrier function by dietary changes might provide an opportunity to modulate the development of RA.
34302046 AHR-dependent genes and response to MTX therapy in rheumatoid arthritis patients. 2021 Oct Methotrexate (MTX) is the first-line therapy for rheumatoid arthritis. Nevertheless, MTX resistance is quite a common issue in clinical practice. There are some premises that aryl hydrocarbon receptor (AhR) gene battery may take part in MTX metabolism. In the present retrospective study, we analyzed genes expression of AHR genes battery associated with MTX metabolism in whole blood of RA patients with good and poor response to MTX treatment. Additionally, sequencing, genotyping and bioinformatics analysis of AHR repressor gene (AHRR) c.565C > G (rs2292596) and c.1933G > C (rs34453673) have been performed. Theoretically, both changes may have an impact on H3K36me3 and H3K27me3. Evolutionary analysis revealed that rs2292596 may be possibly damaging. Allele G in rs2292596 and DAS28 seems to be associated with a higher risk of poor response to MTX treatment in RA. RA patients with poor response to MTX treatment revealed upregulated AhR and SLC19A1 mRNA level. Treatment with IL-6 inhibitor may be helpful to overcome the low-dose MTX resistance. Analysis of gene expression revealed possible another cause of poor response to MTX treatment which is different from that observed in the case of acute lymphoblastic leukemia.
33478953 Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFEL 2021 Jul OBJECTIVES: To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. METHODS: We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region. RESULTS: In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use. CONCLUSIONS: We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.
32514676 Efficacy and safety of switching from reference adalimumab to SB5 in a real-life cohort of 2021 Jan OBJECTIVE: SB5 showed comparable efficacy and safety profile in respect to adalimumab originator (ADA) in randomized clinical trials of rheumatoid arthritis (RA) and psoriasis. We aimed to describe the efficacy and safety of SB5 after switching from ADA in RA, axial spondyloarthritis (axSpA), psoriatic arthritis (PsA) and juvenile idiopathic arthritis (JIA) patients. METHOD: Adult RA, PsA, axSpA, JIA patients treated with ADA for at least 6 months, switched to SB5 in stable clinical conditions, were eligible. Data on safety, activity indexes and patient-reported outcomes were collected at baseline, 3 and 6 months after switching. RESULTS: Eighty-two patients (19 RA, 28 PsA, 32 axSpA and 3 JIA; 45 females, mean age 54 ± 14 years, disease duration 13 ± 7 years, ADA duration 6 ± 3 years) were enrolled. RA patients showed stable conditions, while PsA patients showed an increase in both HAQ, DAS28(CRP) and DAPSA and axSpA patients an increase in VAS pain, VAS patient disease activity and ASDAS, both at 3 months. There were changes in the concomitant medications profile, with regression of activity indexes increases at 6 months. Adverse events were reported by 33.7% patients at 3 months and 16.6% patients at 6 months, mostly disease flares and infectious events. Two patients stopped SB5. CONCLUSIONS: Despite temporary changes in the concomitant medication profile for mild disease flares, our real-life data replicate the safety profile of switching from ADA to SB5 in RA, with additional data for its applicability in PsA and axSpA patients, further supporting switching to biosimilars in treating inflammatory rheumatic conditions. Key Points • Switching from adalimumab originator to SB5 is feasible in real life rheumatic inflammatory joint diseases. • Mild disease flares can present after switching from originator adalimumab to SB5, in particular in axial spondyloarthritis and psoriatic arthritis. • Changes in concomitant medications profile allows the control of minor disease flares presenting after switching from adalimumab originator to SB5.
34465495 Patient involvement in rheumatoid arthritis care to improve disease activity-based managem 2022 May OBJECTIVE: To evaluate the effect of an intervention to improve disease activity-based management of RA in daily clinical practice by addressing patient level barriers. METHODS: The DAS-pass strategy aims to increase patients' knowledge about DAS28 and to empower patients to be involved in treatment (decisions). It consists of an informational leaflet, a patient held record and guidance by a specialized rheumatology nurse. In a Randomized Controlled Trial, 199 RA patients were randomized 1:1 to intervention or control group. Outcome measures were patient empowerment (EC-17; primary outcome), attitudes towards medication (BMQ), disease activity (DAS28) and knowledge about DAS28. RESULTS: Our strategy did not affect EC-17, BMQ, or DAS28 use. However it demonstrated a significant improvement of knowledge about DAS28 in the intervention group, compared to the control group. The intervention had an additional effect on patients with low baseline knowledge compared to patients with high baseline knowledge. CONCLUSION: The DAS-pass strategy educates patients about (the importance of) disease activity-based management, especially patients with low baseline knowledge. PRACTICE IMPLICATIONS: The strategy supports patient involvement in disease activity-based management of RA and can be helpful to reduce inequalities between patients in the ability to be involved in shared decision making.
33441191 Long-term remission and biologic persistence rates: 12-year real-world data. 2021 Jan 13 BACKGROUND: Biologic therapies have greatly improved outcomes in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Yet, our ability to predict long-term remission and persistence or continuation of therapy remains limited. This study explores predictors of remission and persistence of the initial biologic therapy in patients after 12 years. Furthermore, outcomes with adalimumab and etanercept are compared. PATIENTS AND METHODS: RA and PsA patients were prospectively recruited from a biologic clinic. Outcomes on commencing therapy, at 1 year and 12 years were reviewed. Demographics, medications, morning stiffness, patient global health score, tender and swollen joint counts, antibody status, CRP and HAQ were collected. Outcomes at 1 year and 12 years are reported and predictors of biologic persistence and EULAR-defined remission (DAS28-CRP < 2.6) are examined with univariate and multivariate analysis. RESULTS: A total of 403 patients (274 RA and 129 PsA) were analysed. PsA patients were more likely to be male, in full-time employment and have completed higher education. PsA had higher remission rates than RA at both 1 year (60.3% versus 34.5%, p < 0.001) and 12 years (91.3% versus 60.6%, p < 0.001). This difference persisted when patients were matched for baseline disease activity (p < 0.001). Biologic continuation rates were high for RA and PsA at 1 year (49.6% versus 58.9%) and 12 years (38.2% versus 52.3%). In PsA, patients starting on etanercept had lower CRP at 12 years (p = 0.041). Multivariate analysis showed 1-year continuation [OR 4.28 (1.28-14.38)] and 1-year low-disease activity [OR 3.90 (95% CI 1.05-14.53)] was predictive of a 12-year persistence. Persistence with initial biologic at 12 years [OR 4.98 (95% CI 1.83-13.56)] and male gender [OR 4.48 (95% CI 1.25-16.01)] predicted 12 year remission. CONCLUSIONS: This is the first study to show better response to biologic therapy in PsA compared to RA at 12 years. Long-term persistence with initial biologic agent was high and was predicted by biologic persistence and low-disease activity at 1 year. Interestingly, PsA patients had higher levels of employment, educational attainment, and long-term remission rates compared to RA patients.
33787586 Rheumatoid arthritis coexisting with ankylosing spondylitis: A report of 22 cases with del 2021 Apr 2 Coexisting rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in the same patient is often thought to be rare, and thus misdiagnosis is common. The aim of our study was to describe the main characteristics of RA coexisting with AS in patients with delayed diagnoses and improve awareness of the disease association.Between 2012 and 2018, data from 22 patients who had RA and AS (RA/AS) were retrospectively reviewed. All patients had a history of delayed diagnosis for RA or AS. The clinical features and radiographic changes of RA and AS patients were obtained at baseline and after 2 years. Disease activity score 28 (DAS28) or bath ankylosing spondylitis disease activity index (BASDAI) were used as outcome measures. The mean age at the time of diagnosis of RA/AS was 51.8 years, while the mean duration of diagnostic delay was 5.5 years. Middle-aged women were the most common subgroup among the RA/AS cohort. The common clinical manifestations were systemic, symmetric, peripheral, and axial arthritis. The erythrocyte sedimentation rate and C-reactive protein levels in RA/AS patients were elevated at the time diagnosis of RA/AS. The typical radiologic changes for the 2 diseases coexisted in RA/AS patients. The DAS28 and BASDAI scores at the 2-year follow-up evaluation were lower than the initial assessment.Coexisting RA and AS is often misdiagnosed for many years; a lack of recognition of RA and AS together is one of the most common reasons. Systemic, symmetric, peripheral, and axial arthritis in middle-aged women were the most frequent presentations at onset.
34158089 Handwork vs machine: a comparison of rheumatoid arthritis patient populations as identifie 2021 Jun 22 BACKGROUND: Electronic health records (EHRs) offer a wealth of observational data. Machine-learning (ML) methods are efficient at data extraction, capable of processing the information-rich free-text physician notes in EHRs. The clinical diagnosis contained therein represents physician expert opinion and is more consistently recorded than classification criteria components. OBJECTIVES: To investigate the overlap and differences between rheumatoid arthritis patients as identified either from EHR free-text through the extraction of the rheumatologist diagnosis using machine-learning (ML) or through manual chart-review applying the 1987 and 2010 RA classification criteria. METHODS: Since EHR initiation, 17,662 patients have visited the Leiden rheumatology outpatient clinic. For ML, we used a support vector machine (SVM) model to identify those who were diagnosed with RA by their rheumatologist. We trained and validated the model on a random selection of 2000 patients, balancing PPV and sensitivity to define a cutoff, and assessed performance on a separate 1000 patients. We then deployed the model on our entire patient selection (including the 3000). Of those, 1127 patients had both a 1987 and 2010 EULAR/ACR criteria status at 1 year after inclusion into the local prospective arthritis cohort. In these 1127 patients, we compared the patient characteristics of RA cases identified with ML and those fulfilling the classification criteria. RESULTS: The ML model performed very well in the independent test set (sensitivity=0.85, specificity=0.99, PPV=0.86, NPV=0.99). In our selection of patients with both EHR and classification information, 373 were recognized as RA by ML and 357 and 426 fulfilled the 1987 or 2010 criteria, respectively. Eighty percent of the ML-identified cases fulfilled at least one of the criteria sets. Both demographic and clinical parameters did not differ between the ML extracted cases and those identified with EULAR/ACR classification criteria. CONCLUSIONS: With ML methods, we enable fast patient extraction from the huge EHR resource. Our ML algorithm accurately identifies patients diagnosed with RA by their rheumatologist. This resulting group of RA patients had a strong overlap with patients identified using the 1987 or 2010 classification criteria and the baseline (disease) characteristics were comparable. ML-assisted case labeling enables high-throughput creation of inclusive patient selections for research purposes.
33025632 The roles of small-molecule inflammatory mediators in rheumatoid arthritis. 2021 Mar Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Although great progress has been made in the treatment of RA with antagonists of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1, the disease remains refractory in some patients. Previous studies have found that small-molecule inflammatory mediators, such as prostaglandins, leukotrienes, reactive oxygen species, nitric oxide, lipoxins and platelet-activating factor, play a significant role in the development of RA. Such compounds help to induce, maintain or reduce inflammation and could therefore be potential therapeutic targets. In this review, we describe the roles of various classes of small-molecule inflammatory mediators in RA and discuss the effects of some drugs that modulate their activity. Many drugs targeting these mediators have demonstrated good efficacy in mouse models of RA but not in patients. However, it is clear that many small-molecule inflammatory mediators play key roles in the pathogenesis of RA, and a better understanding of the underlying molecular pathways may assist in the development of targeted therapies that are efficacious in RA patients.
34846489 ROS-mediated liposomal dexamethasone: a new FA-targeted nanoformulation to combat rheumato 2021 Dec 13 Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder that has seriously affected human health worldwide and its current management requires more successful therapeutic approaches. The combination of nanomedicines and pathophysiology into one system may provide an alternative strategy for precise RA treatment. In this work, a practical ROS-mediated liposome, abbreviated as Dex@FA-ROS-Lips that comprised synthetic dimeric thioether lipids (di-S-PC) and a surface functionalized with folic acid (FA), was proposed for dexamethasone (Dex) delivery. Incorporation with thioether lipids and a FA segment significantly improved the triggered release and improved the triggered release of cytotoxic Dex as well as the active targeting of RA, altering its overall pharmacokinetics and safety profiles in vivo. As proof, the designed Dex@FA-ROS-Lips demonstrated effective internalization by LPS-activated Raw264.7 macrophages with FA receptor overexpression and released Dex at the inflammatory site due to the ROS-triggered disassembly. Intravenous injection of this Dex@FA-ROS-Lips into adjuvant-induced arthritis (AIA) mice led to its incremental accumulation in inflamed joint tissues and significantly alleviated the cartilage destruction and joint swelling via suppression of proinflammatory cytokines (iRhom2, TNF-α and BAFF), as compared to the effect of commercial free Dex. Importantly, the Dex@FA-ROS-Lips nanoformulation showed better hemocompatibility with less adverse effects on the body weight and immune organ index of AIA mice. The anti-inflammatory mechanism of Dex@FA-ROS-Lips was further studied and it was found that it is possibly associated with the down-regulation of iRhom2 and the activation of the TNF-α/BAFF signaling pathway. Therefore, the integration of nanomedicines and the RA microenvironment using multifunctional Dex@FA-ROS-Lips shall be a novel RA treatment modality with full clinical potential, and based on the enhanced therapeutic effect, the signaling pathway of iRhom2/TNF-α/BAFF reasonably explained the mechanism of Dex@FA-ROS-Lips in anti-RA, which suggested a molecular target for RA therapy and other inflammatory diseases.
33956894 Health care costs of rheumatoid arthritis: A longitudinal population study. 2021 Quantifying the contribution of rheumatoid arthritis to the acquisition of subsequent health care costs is an emerging focus of the rheumatologic community and payers of health care. Our objective was to determine the healthcare costs before and after diagnosis of rheumatoid arthritis (RA) from the public payer's perspective. The study design was a longitudinal observational administrative data-based cohort with RA cases from Ontario Canada (n = 104,933) and two control groups, matched 1:1 on year of cohort entry from 2001 to 2016. The first control group was matched on age, sex and calendar year of cohort entry (diagnosis year for those with RA); the second group added medical history to the match before RA diagnosis year. The main exposure was new onset RA. The secondary exposure was calendar year of RA diagnosis to compare attributable costs over the study observation window. Main outcomes were health care costs in 2015 Canadian dollars, overall and by cost category. We used attribution methods to classify costs into those associated with RA, those associated with comorbidities, and age/sex-related underlying costs. Health care costs associated with RA increased up to the year of diagnosis, where they reached $8,591: $4,142 in RA associated costs; $1,242 in RA comorbidity associated costs; and $3,207 in underlying costs. In the eighth-year post diagnosis, the RA costs declined to $2,567 while the RA comorbidity associated costs remained relatively constant at $1,142, and the underlying age/sex related cost increased to $4,426. RA patients had lower costs when diagnosed in later calendar years. Our results suggest a large proportion of disease related health care costs are a result of costs associated with RA comorbidities, which may appear many years before diagnosis.