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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| 33538487 | Effects of Laser Therapy on Rheumatoid Arthritis: A Systematic Review and Meta-analysis. | 2021 Nov 1 | OBJECTIVE: The aim of the study was to examine the effects of laser therapy on rheumatoid arthritis. DESIGN: A search of controlled trials was conducted in different medical electronic databases. The primary outcome was immediate pain relief after treatment. Secondary outcomes were level of functional disability, morning stiffness duration, and 3-mo follow-up for pain. RESULTS: Ten trials met the inclusion criteria. Rheumatoid arthritis treatment with laser therapy significantly improved immediate pain relief (standardized mean difference = -0.839, 95% confidence interval = -1.336 to -0.343) and overall functional score (standardized mean difference = -0.309, 95% confidence interval = -0.587 to -0.031). There was no significant improvement in morning stiffness duration (standardized mean difference = -0.519, 95% confidence interval = -1.176 to 0.138), and 3-mo follow-up for pain (standardized mean difference = -1.125, 95% confidence interval = -2.311 to 0.061). There was no publication bias (Egger regression, P = 0.277). However, heterogeneity was noted despite the removal of an outlier (Q = 18.646, I2 = 57.096). Results of subgroup analyses suggested that high-intensity laser therapy and nerve irradiation are better suited for immediate pain relief. Meta-regression analyses showed no significant linear relationship between the treatment effect with laser wavelength or number of treatment sessions. CONCLUSIONS: Laser therapies provide significant immediate pain relief and improve function for rheumatoid arthritis patients, but without significant improvement in morning stiffness duration and 3-mo follow-up for pain.Systematic review registration number: CRD42020192906. | |
| 33314707 | Clinical impact of musculoskeletal ultrasound on rheumatoid arthritis in routine care. | 2021 Mar | OBJECTIVE: To evaluate the impact of musculoskeletal ultrasound (MSUS) in the management of rheumatoid arthritis (RA) patients and to investigate factors affecting treatment strategy by the referring rheumatologist. METHODS: Prospective study of RA patients evaluated at a MSUS clinic over a 6-month period. Data extraction included demographics, current treatment and MSUS findings. Pre- and post-MSUS follow-up of 3 months data were analyzed. Patients were classified into 2 groups based on the decision of the referring rheumatologist to change the treatment after the MSUS examination. Comparisons between groups were performed in a univariate analysis. We used logistic regression models to investigate factors associated with changes in clinical management. RESULTS: A total of 64 RA patients were included. Mean age was 61.9 years and 83.6% were female. Main referral indication was assessment of disease activity (89%). Overall, MSUS led to subsequent therapeutic actions by the referring rheumatologist in 41 (64.1%) patients, and to a change in the clinical impression of the complaint that generated the referral in 7 (11.5%) patients. The detection of power Doppler (PD), the 28 swollen joint count and the presence of radiographic erosions were significantly associated with a subsequent clinical action. In the multivariate analysis only PD remained significant (odds ratio = 3.29; 95% CI: 1.05-10.26). CONCLUSION: Disease activity evaluation is the most common indication for MSUS examination, with the presence of PD the factor most frequently associated with changes in therapeutic management. This study highlights the impact of MSUS, especially the use of PD, to support treatment decisions in RA routine care. | |
| 34838812 | Evaluation of the therapeutic efficacy of human bone marrow mesenchymal stem cells with CO | 2022 Jan 1 | OBJECTIVE: Mesenchymal stem cells (MSCs), especially genetically modified MSCs, have become a promising therapeutic approach for the treatment of rheumatoid arthritis (RA) through modulating immune responses. However, most MSCs used in the treatment of RA are modified based on a single gene. In this study, we evaluated the therapeutic effects of human BMSCs (hBMSCs) with COX-2 silence and TGF-β3 overexpression in the treatment of RA in a rabbit model. MATERIALS AND METHODS: hBMSCs were cotransfected with shCOX-2 and TGF-β3 through lentiviral vector delivery. After SPIO-Molday ION Rhodamine-B™ (MIRB) labeling, lenti-shCOX2-TGF-β3 hBMSCs, lenti-shCOX2 hBMSCs, lenti-TGF-β3 hBMSCs, hBMSCs without genetic modification, or phosphate-buffered saline (PBS) were injected into the knee joint of rabbits with antigen-induced arthritis (AIA). The diameter of the knee joint and soft-tissue swelling score (STS) were recorded, and the levels of inflammatory mediators, including interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) were evaluated by ELISA. Clinical 3.0T MR imaging (MRI) was used to track the distribution and dynamic migration of hBMSCs in the joint. Histopathological and immunohistochemical assays were conducted to localize labeled hBMSCs and assess the alteration of synovial hyperplasia, inflammatory cell infiltration, and cartilage damage. RESULTS: COX-2 silencing and TGF-β3 overexpression in hBMSCs were confirmed through real-time PCR and Western blot analyses. Reduced joint diameter, soft-tissue swelling (STS) score, and PGE2, IL-1β, and TNF-α expression were detected 4 weeks after injection of MIRB-labeled lenti-shCOX2-TGF-β3 hBMSCs into the joint in rabbits with AIA. Eight weeks after hBMSC injection, reduced inflammatory cell infiltration, improved hyperplasia of the synovial lining, recovered cartilage damage, and increased matrix staining were observed in joints injected with lenti-shCOX2-TGF-β3 hBMSCs and lenti-shCOX2 hBMSCs. Slight synovial hyperplasia, no surface fibrillation, and strong positive expression of collagen II staining in chondrocytes and cartilage matrix were detected in the joints 12 weeks after injection of lenti-shCOX2-TGF-β3 hBMSCs. In addition, hBMSCs were detected by MRI imaging throughout the process of hBMSC treatment. CONCLUSION: Intra-articular injection of hBMSCs with COX-2 silence and TGFβ3 overexpression not only significantly inhibited joint inflammation and synovium hyperplasia, but also protected articular cartilage at the early stage. In addition, intra-articular injection of hBMSCs with COX-2 silence and TGFβ3 overexpression promoted chondrocyte and matrix proliferation. This study provides an alternative therapeutic strategy for the treatment of RA using genetically modified hBMSCs. | |
| 34418899 | Evaluation of TAK-242 (Resatorvid) Effects on Inflammatory Status of Fibroblast-like Synov | 2021 Aug 7 | Fibroblast-like synoviocytes (FLSs) produce lots of inflammatory molecules that trigger immune responses and intensification the inflammation and thereby play important roles in Rheumatoid Arthritis )RA( pathogenesis. Due to the important roles of toll-like receptor 4 (TLR4) in cytokine production and inflammation, we aimed to evaluate the effects of TAK-242 (Resatorvid) on interleukin (IL)1-β, IL-6, TNF-α, and TLR4 expression and two important proteins of nuclear factor-κB (NF-κB) signaling pathway (Ikβα and pIkβα) in RA and trauma FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients and cultured in Dulbecco's Modified Eagle Medium (DMEM). 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the cytotoxicity effects of TAK-242 on the RA FLSs. Real-time PCR was performed to measure the expression level of IL1-β, IL-6, TNF-α, and TLR4 genes in Lipopolysaccharide (LPS) and TAK-242 treated FLSs. Furthermore, the treated FLSs were evaluated for protein levels of Ikβα and pIkβα by western blot. The baseline expression of IL1-β, IL-6, TNF-α, and TLR4 showed no significant differences between healthy and RA FLSs. LPS stimulated FLSs significantly increased mRNA levels of IL-1β, IL-6, TNF-α, and TLR4 genes in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. Furthermore, LPS-stimulated FLSs significantly increased the level of pIkβα in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. We provide the data that TAK-242 through inhibiting the NF-κB signaling pathway may modulate TLR4-mediated inflammatory responses and could be considered as a potential therapeutic agent for RA patients. | |
| 32856510 | Disease activity trajectories in rheumatoid arthritis: a tool for prediction of outcome. | 2021 Jan | Objective: Predicting treatment response and disease progression in rheumatoid arthritis (RA) remains an elusive endeavour. Identifying subgroups of patients with similar progression is essential for understanding what hinders improvement. However, this cannot be achieved with response criteria based on current versus previous Disease Activity Scores, as they lack the time component. We propose a longitudinal approach that identifies subgroups of patients while capturing their evolution across several clinical outcomes simultaneously (multi-trajectories). Method: For exploration, the RA cohort BARFOT (n = 2829) was used to identify 24 month post-diagnosis simultaneous trajectories of 28-joint Disease Activity Score and its components. Measurements were available at inclusion (0), 3, 6, 12, 24, and 60 months. Multi-trajectories were found with latent class growth modelling. For validation, the TIRA-2 cohort (n = 504) was used. Radiographic changes, assessed by the modified Sharp van der Heijde score, were correlated with trajectory membership. Results: Three multi-trajectories were identified, with 39.6% of the patients in the lowest and 18.9% in the highest (worst) trajectory. Patients in the worst trajectory had on average eight tender and six swollen joints after 24 months. Radiographic changes at 24 and 60 months were significantly increased from the lowest to the highest trajectory. Conclusion: Multi-trajectories constitute a powerful tool for identifying subgroups of RA patients and could be used in future studies searching for predictive biomarkers for disease progression. The evolution and shape of the trajectories in TIRA-2 were very similar to those in BARFOT, even though TIRA-2 is a newer cohort. | |
| 34782657 | Middle east pain syndrome is a pollution-induced new disease mimicking rheumatoid arthriti | 2021 Nov 15 | Musculoskeletal pains are sometimes misdiagnosed in some diseases, like rheumatoid and psoriatic arthritis, erosive OA, etc. Secondary hyperparathyroidism was not considered a differential diagnosis for RA, despite the fact that it can cause arthralgia or arthritis. Also, fibromyalgia is a psychosomatic condition marked by widespread pain and tenderness. This study included 400 patients attended certain outpatient clinics of Rheumatology in Egypt and Saudi Arabia, who were not fulfilling criteria for RA diagnosis. Criteria for classification of fibromyalgia syndrome were applied to all patients. We did lab tests and radiological imaging modalities for diagnosis or exclusion of suspected diseases were applied. All patients were fulfilling both old and new criteria of fibromyalgia syndrome, and not fulfilling any RA criteria, and had vitamin D3 deficiency or insufficiency. 75% of patients had abnormally high levels of PTH, without parathyroid gland pathology. Radiology showed subperiosteal and subchondral resorption of mainly thumbs, subchondral osteopenia of proximal and middle phalanges, mild subperiosteal resorption along the radial aspect of the middle phalanx and mild tuft erosions, besides changes in the carpus closely resembling those of rheumatoid arthritis, of ulnar styloid resorption, radiocarpal and scapho-trapezoid joint arthritis. Of special interest, the presence of tuft spur-like excrescences. | |
| 32754755 | The Association Between Serum Leptin Levels and Cardiovascular Events in Patients with Rhe | 2021 Jan 4 | OBJECTIVE: Cardiovascular diseases (CVDs) are important complications for patients with rheumatoid arthritis (RA). The study aimed to explore whether serum leptin is associated with a increased risk of cardiovascular (CV) events in patients with RA. METHODS: Two hundred twenty-three patients with RA were followed for a mean of 40 (range = 8-42) months. Serum leptin levels were measured at baseline. Cox regression analysis was performed to assess the association between leptin levels and the risk of CV events. RESULTS: The univariate analysis showed that patients with RA with higher serum leptin levels had higher rates of CV events and CV mortality, respectively (P <.001). The logistic regression model showed that leptin was independently related to CVD history (odds ratio = 1.603, 95% confidence interval [CI], 1.329-2.195; P =.005) after adjusting for confounding factors in patients with RA at baseline. The multivariate Cox proportional hazard model suggested that leptin was an independent prognostic factor for CV events in patients with RA after adjustments were made for clinical confounding factors (hazard ratio = 2.467, 95% CI, 2.019-4.495; P <.001). The Kaplan-Meier analysis showed that compared with patients with RA with leptin levels below the median value (≤15.4 mg/L), patients with leptin above the median value (>15.4 μg/L) had a higher rate of CV events (P <.001). CONCLUSION: Leptin was significantly associated with CV events in patients with RA. Elevated serum leptin levels may be a reliable prognostic factor for predicting CV complications in patients with RA. | |
| 33231330 | Metabolic syndrome in rheumatoid arthritis patients: Relationship among its clinical compo | 2021 Mar | BACKGROUND: Metabolic syndrome (MetS) prevalence in rheumatoid arthritis (RA) patients is known to vary considerably across the world. This study aimed to determine the prevalence of MetS in RA patients from western Mexico and to analyze the interrelation of the MetS components with the clinical variables of RA. METHODS: This case-control study included 216 RA patients and 260 control subjects (CS). MetS prevalence was determined according to the NCEP/ATP III and the Latin American Consensus of the Latin American Diabetes Association (ALAD) criteria. RESULTS: MetS was observed in 30.6% RA patients and 33.3% of controls (p > 0.05) according to NCEP/ATP III and 28.7% in RA patients and 31.1% for controls using ALAD criteria. Total cholesterol, LDL-C, and Castelli's I-II indexes were lower in RA (p < 0.001) than in CS. The RA patients with MetS had more swollen joints than those without MetS (p = 0.018). In RA patients with MetS, DAS-28 score correlated with smoking index (rho = 0.4601, p = 0.0004) and VLDL-C (rho = 0.3108, p = 0.0056); similarly, rheumatoid factor (RF) correlated with age (rho = 0.2031, p = 0.0027), smoking index (rho = 0.3404, p < 0.0001), triglycerides (rho = 0.1958, p = 0.0039), and VLDL-C (rho = 0.1761, p = 0.0162). CONCLUSIONS: The MetS prevalence in RA patients from western Mexico is not higher than controls; however, in RA patients with MetS, some inflammatory markers are associated with MetS components; thus, the control of MetS in RA could be beneficial to regulate disease activity. | |
| 33191282 | Does Including Pain, Fatigue, and Physical Function When Assessing Patients with Early Rhe | 2021 Feb | OBJECTIVE: To explore the possibility of integrating patient-important outcomes like pain, fatigue, and physical function into the evaluation of disease status in early rheumatoid arthritis (ERA) without compromising correct disease activity measurement. METHODS: Patients from the 2-year Care in Early Rheumatoid Arthritis (CareRA) trial were included. Pain and fatigue (visual analog scales), Health Assessment Questionnaire (HAQ), standard components of disease activity [swollen/tender joint counts (SJC/TJC), C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), physician (PhGH) and patient (PaGH) global health] were recorded at every visit (n = 10). Pearson correlation and exploratory factor analyses (EFA), using multiple imputation (15×) and outputation (1000×), were performed per timepoint and overall, on standard components of disease activity scores with and without pain, fatigue, and HAQ. Each of the 15,000 datasets was analyzed using EFA with principal component extraction and oblimin rotation to determine which variables belong together. RESULTS: We included 379 patients. EFA on standard composite score components extracted 2 factors with no substantial cross-loadings. Still, pain (0.83), fatigue (0.65), and HAQ (0.59) were strongly correlated with PaGH. When rerunning the EFA with the inclusion of pain, fatigue, and HAQ, the 2-factor model had substantial cross-loadings between factors. However, a 3-factor model was optimal, with Factor 1: patient assessment, Factor 2: clinical assessment (PhGH, SJC, and TJC), and Factor 3: laboratory assessment (ESR/CRP). CONCLUSION: PaGH, pain, fatigue, and physical function represent a separate aspect of the disease burden of patients with ERA, which could be further explored as a target for care apart from disease activity. [ClinicalTrials.gov: NCT01172639]. | |
| 33963063 | Physical activity in patients with rheumatoid arthritis - an agile lifelong behaviour: a q | 2021 May | BACKGROUND: Physical activity (PA) in rheumatoid arthritis (RA) is considered a cornerstone in the treatment. To highlight aspects involved in supporting a positive PA behaviour, it is important to understand the patients' perceptions of the phenomenon. OBJECTIVE: The aim of this qualitative meta-synthesis was to explore and synthesise patient perceptions of PA in RA. METHODS: A purposeful search was conducted across three online databases (PubMed, CINAHL and Web of Science). The methodological quality of the included studies was appraised, and data were extracted and analysed using an interpretive inductive thematic synthesis. RESULTS: Fifteen studies met the inclusion criteria and were included. PA was identified as an agile lifelong behaviour, with one main theme: The disease as a persistent catalyst for or against PA illustrating how the constant presence of the disease itself underlies the entire process of a life with or without regular PA. Seven subthemes: 'considering aggravated symptoms', 'acknowledging the impact on health', 'becoming empowered and taking action', 'keeping informed to increase awareness', 'creating body awareness', 'dealing with social support' and 'feeling satisfied with circumstances and achievements' were interpreted as facilitators and/or challenges. CONCLUSION: This synthesis has identified PA as an agile lifelong behaviour in which the disease pervades all aspects of an individuals' perception of PA. Placed in a theoretical context, our findings outline a model for tailoring PA support to the drivers and determinants of a certain individual, which will improve clinical practice for the benefit of both health professionals and patients with RA. | |
| 33918929 | Sustained Hypoxia Suppresses Joint Destruction in a Rat Model of Rheumatoid Arthritis via | 2021 Apr 9 | Hypoxia inducible factor (HIF)-1α has been implicated in the pathogenesis of rheumatoid arthritis (RA). HIF-1α, which is expressed in hypoxia, is reversely suppressed in sustained hypoxia. Here, we investigated the inhibitory effect of hypoxia on arthritis by controlling HIF-1α. Rheumatoid fibroblast-like synoviocyte MH7A cells were cultured in a hypoxic incubator for up to 72 h to evaluate the expression of HIF-1. Furthermore, collagen-induced arthritis (CIA) model rats were maintained under 12% hypoxia in a hypoxic chamber for 28 days to evaluate the effect on arthritis. In MH7A cells, HIF-1α protein level increased at 3 h, peaked at 6 h, and subsequently decreased in a time-dependent manner. The transcription of pro-inflammatory cytokines increased at 1 h; however, they decreased after 3 h (p < 0.05). Deferoxamine-mediated activation of HIF-1α abolished the inhibitory effect of sustained hypoxia on pro-inflammatory cytokines. In the rat CIA model, the onset of joint swelling was delayed and arthritis was suppressed in the hypoxia group compared with the normoxia group (p < 0.05). Histologically, joint destruction was suppressed primarily in the cartilage. Thus, sustained hypoxia may represent a new safe, and potent therapeutic approach for high-risk patients with RA by suppressing HIF-1α expression. | |
| 33967602 | Morpho-structural characteristics of feet in patients with rheumatoid arthritis: A cross s | 2021 | Objective: The aim of this study was to evaluate and classify the types and incidences of foot deformities in patients with Rheumatoid Arthritis (RA). Methods: A cross-sectional study with convenience sample was obtained of 220 patients with foot pain and RA classification criteria (approved by the American College of Rheumatology and the European League against Rheumatism in 2010). A series of outcomes were assessed to measure the morphological characteristics of the feet. The Foot Posture Index (FPI), the Manchester Scale of Hallux Valgus and the Nijmegen classification of forefoot disorders were assessed. Results: The most common foot posture according to the FPI assessment are the pronated position in the left foot (32.7% of participants) and the neutral position in the right foot (34.1% of participants). The disease progression causes more developed and serious foot deformities. 1.82% of patients present a severe level of Hallux Valgus before 10 years of disease evolution whereas 4.09% of patients present a severe level of Hallux Valgus after 10 years of disease evolution. Conclusions: The most common foot type in patients with RA is the pronated foot type with deformities in the MTP joints without Hallux Valgus. However, a percentage of patients with RA presents supinated foot type. The evolution of the disease shows some morphological changes in terms of patient's feet. The presence of more developed foot deformities is increased, such us Hallux Valgus or MTP joints deformity (Grade 3 in the Nijmegen classification scale). | |
| 33159378 | Joint damage in rheumatoid arthritis: Lessons learned from an extended 36-joint ultrasonog | 2021 Jan | AIM: To study joint damage severity in rheumatoid arthritis (RA) patients classified using ultrasound power Doppler (PD) and gray-scale (GS) joint inflammation outcomes and the 28-joint Disease Activity Score (DAS28). METHOD: Ultrasound erosion scores were compared between (a) patients in group 1 (PD positive and GS ≥ median score), group 2 (PD negative and GS ≥ median score) and group 3 (PD positive and GS < median score) vs group 4 (PD negative and GS < median score) and (b) patients with high, moderate and low DAS28 scores vs those in DAS28 remission. Comparative analyses were performed using the 2-sample Student's t test. RESULTS: There were 1080 joints and 1800 joint recesses from 36 joints scanned in 30 RA adult patients (mean DAS28, 3.58; mean disease duration, 70.3 months) in this cross-sectional study. The mean and 95% CI ultrasound erosion scores were significantly higher (P = .026) for groups 1 (9.75, 6.69-12.81) vs 4 (3.4, 1.11-5.69) with a difference (95% CI) of 6.35 (0.78-11.83), but not significantly different (P values all > .05) for (a) groups 2 and 3 vs 4 and (b) patients with high, moderate and low DAS28 scores vs those in DAS28 remission. CONCLUSION: Severity of ultrasound-detected bone erosions was significantly greater when both positive PD and a greater degree of GS joint inflammation were present in RA. This association was not observed when either component was absent. Single time point ultrasound joint inflammation assessment - and not DAS28 - is reflective of joint damage severity in RA patients. | |
| 33510042 | Efficacy and safety of rituximab in peripheral ulcerative keratitis associated with rheuma | 2021 Jan | OBJECTIVE: Peripheral ulcerative keratitis (PUK) is a rare but severe ocular complication of rheumatoid arthritis (RA). It can be considered as an ocular manifestation of rheumatoid vasculitis (RV). Our case series aimed to evaluate the efficacy of rituximab (RTX) for PUK occurring in patients with RA. METHODS: Study population were patients with RA-associated PUK treated with RTX 1000 mg on days 1 and 15 at least once after the diagnosis. We identified patients referred to the rheumatology and ophthalmology departments of our hospital between February 2014 and June 2020. We also included patients referred by their specialist after being contacted through the Club Rhumatismes et Inflammation. Demographic data and clinical and biological features were retrospectively collected. RESULTS: We included seven patients (three men and four women, median age 58 years). All but one had a long-standing RA with a median disease duration of 13.9 years (IQR 0-30.2). RA was erosive in six out of seven patients. All patients had rheumatoid factors and anticitrullinated peptides antibodies were positive in six of them. PUK was complicated by corneal perforation in three patients and required surgery. After a median follow-up of 29.8 months (IQR 5-75), corneal inflammation was controlled in all patients. PUK recurred in one patient, 8 months after a single infusion of RTX. 71% of the patients presented a good articular response. No patient developed other manifestations of RV. No serious adverse event related to RTX was observed. CONCLUSION: RTX appears to be an efficient and safe therapeutic option in the treatment of RA-associated PUK. | |
| 33844107 | The positive effect of pregnancy in rheumatoid arthritis and the use of medications for th | 2021 Aug | Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disorder that is mostly characterised by progressive symmetrical joint destruction, particularly in the wrist and fingers, while it may also affect additional joints and several organs, such as the skin, heart, blood vessels, and lungs. It is identified by raised anti-rheumatoid factor and anti-cyclic citrullinated peptide antibodies. The chemical mediators involved in the activity of RA are IL-1β, TNF-α, and IL-6. Pregnancy exerts a positive effect on RA that helps to modulate the disease condition. Different hypotheses are recommended to explain the ameliorating effect of pregnancy in RA. RA cannot be completely cured. The treatment goal is the attrition of pain and inflammation and the further progression of the disease. Long-term management of RA is carried out using disease-modifying antirheumatic drugs (DMARDs). Therapy of acute flares can be done with Non-steroidal anti-inflammatory drugs (NSAIDs) accompanied by ad interim usage of glucocorticoids. Biologic response modifiers are also available; they act by abolishing the activity of T- cells. However, it is necessary to select the correct treatment regimen when it comes to the management of RA in pregnancy. | |
| 33323534 | The Clinical Disease Activity Index and the Routine Assessment of Patient Index Data 3 for | 2021 Dec | OBJECTIVE: To compare the Clinical Disease Activity Index (CDAI) with the Routine Assessment of Patient Index Data 3 (RAPID3) from 2 large United States registries. METHODS: Using a cross section of clinic visits within 2 registries, we determined whether the outcome of each metric would place the patient in remission (REM), low (LDA), moderate (MDA), or high disease activity (HDA) using the CDAI, with the assumption that a patient in MDA or HDA would be a candidate for acceleration of treatment. RESULTS: We identified significant disparities between the 2 indices in final disease categorization using each index system. For patients identified in LDA by CDAI, RAPID3 identified 20.4% and 28.3% as LDA in Corrona and the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS), respectively. For patients identified as MDA by CDAI, RAPID3 identified 36.2% and 31.1% as MDA in Corrona and BRASS, respectively, with the greatest disparities within each system identified for LDA and MDA activity by the CDAI (20.4% and 36.2% agreement of RAPID3 with CDAI, respectively, in Corrona and 28.3% and 31.1% agreement in BRASS). Overall comparison between CDAI and RAPID3 in the 4 disease categories resulted in estimated κ = 0.285 in both. The RAPID3 scores indicated the potential for treat-to-target acceleration in 34.4% of patients in REM or LDA based on CDAI in Corrona and 27.7% in BRASS, respectively. CONCLUSION: The RAPID3, based on patient-reported outcomes, shows differences with CDAI categories of disease activity. The components of CDAI are not highly correlated with RAPID3, except for patient global assessment. These differences could significantly affect the decision to advance treatment when using a treat-to-target regimen. | |
| 33732263 | Multipotent Mesenchymal Stromal Cells in Rheumatoid Arthritis and Systemic Lupus Erythemat | 2021 | The pathogenesis of the autoimmune rheumatological diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is complex with the involvement of several immune cell populations spanning both innate and adaptive immunity including different T-lymphocyte subsets and monocyte/macrophage lineage cells. Despite therapeutic advances in RA and SLE, some patients have persistent and stubbornly refractory disease. Herein, we discuss stromal cells' dual role, including multipotent mesenchymal stromal cells (MSCs) also used to be known as mesenchymal stem cells as potential protagonists in RA and SLE pathology and as potential therapeutic vehicles. Joint MSCs from different niches may exhibit prominent pro-inflammatory effects in experimental RA models directly contributing to cartilage damage. These stromal cells may also be key regulators of the immune system in SLE. Despite these pro-inflammatory roles, MSCs may be immunomodulatory and have potential therapeutic value to modulate immune responses favorably in these autoimmune conditions. In this review, the complex role and interactions between MSCs and the haematopoietically derived immune cells in RA and SLE are discussed. The harnessing of MSC immunomodulatory effects by contact-dependent and independent mechanisms, including MSC secretome and extracellular vesicles, is discussed in relation to RA and SLE considering the stromal immune microenvironment in the diseased joints. Data from translational studies employing MSC infusion therapy against inflammation in other settings are contextualized relative to the rheumatological setting. Although safety and proof of concept studies exist in RA and SLE supporting experimental and laboratory data, robust phase 3 clinical trial data in therapy-resistant RA and SLE is still lacking. | |
| 31789997 | Cultural Adaptation and Validation of the Methotrexate Intolerance Severity Score in Brazi | 2021 Sep 1 | INTRODUCTION: The Methotrexate Intolerance Severity Score (MISS) questionnaire is used to identify intolerance to methotrexate (MTX), but it is not available in the Brazilian Portuguese language. OBJECTIVE: The aim of this study was to adapt and validate the MISS in Brazilian Portuguese. METHODS: The Brazilian Portuguese version of the MISS was developed following the Guidelines for the Process of Cross-cultural Adaptation of Self-report Measures. The new version was tested in 120 patients with rheumatoid arthritis. For the reliability assessment, the Cronbach α coefficient was used. The receiver operating characteristic curve was constructed with the objective of finding the best cutoff point for MTX intolerance and weighing the sensitivity and specificity. The concordance among the results was analyzed using the κ coefficient and factorial analysis with varimax rotation. RESULTS: This methodological study developed and applied a culturally acceptable Brazilian Portuguese version of the MISS. The MISS questionnaire presented internal consistency classified as "very good" because Cronbach α is equal to 0.83 (95% confidence interval, 0.79-0.87). The suitability of the data for factorial analysis was demonstrated using the Kaiser-Meyer-Olkin sample adequacy test (KMO = 0.723) and Bartlett sphericity test (χ2 = 499.98, p < 0.001). It was observed that a factorial analysis with 3 factors is preferred; the receiver operating characteristic curve of the MISS score was considered the cutoff point at 6 points (sensitivity 100% and specificity 89.4%). CONCLUSIONS: The Brazilian Portuguese version of the MISS is valid and reliable for the detection of MTX intolerance in clinical practice. | |
| 32552188 | Disease activity affects the recurrent deformities of the lesser toes after resection arth | 2021 Mar | OBJECTIVES: The purpose of this study was to clarify the effect of disease activity on recurrent deformities after resection arthroplasty for forefoot deformities in patients with rheumatoid arthritis (RA). METHODS: This study included 83 feet in 58 patients with RA who underwent resection arthroplasty of all metatarsal heads, with a minimum follow-up of 2 years. The patients' demographic characteristics, preoperative radiographic findings, and RA disease activity evaluated using the 28-joint disease activity score based on the erythrocyte sedimentation rate (determined preoperatively and at the final follow-up) were compared between feet with and without postoperative recurrent deformities of the toes. Recurrent deformities were assessed separately for the hallux and lesser toes. RESULTS: Recurrence in the hallux and lesser toes occurred in 23 feet (27.7%) and 13 feet (15.7%), respectively. With respect to recurrent hallux deformity, only the preoperative severity of hallux deformity was associated with recurrence. On the other hand, postoperative deformity of the lesser toes was positively associated with disease activity alone and not with other preoperative factors. CONCLUSION: Postoperative control of RA disease activity was associated with recurrent deformity of the lesser toes but not that of the hallux after resection arthroplasty of all metatarsals for rheumatoid forefoot deformities. | |
| 34418490 | Polarization of rheumatoid macrophages is regulated by the CDKN2B-AS1/ MIR497/TXNIP axis. | 2021 Nov | The polarization of macrophages plays a critical role in the pathophysiology of rheumatoid arthritis. The macrophages can have pro-inflammatory M1 polarization and various types of alternative anti-inflammatory M2 polarization. Our preliminary results showed that the CDKN2B-AS1/MIR497/TXNIP axis might regulate macrophages of rheumatoid arthritis patients. Therefore, we hypothesized that this axis regulated the polarization of rheumatoid macrophages. Flow cytometry was used to determine the surface polarization markers in M1 or M2 macrophages from healthy donors and rheumatoid arthritis patients. The QPCR and Western Blotting were used to compare the expression of the CDKN2B-AS1/MIR497/TXNIP axis in these macrophages. We Knocked down and overexpressed the axis in the macrophage cell line MD to test its roles in macrophage polarization. Compared to cells from healthy donors, cells from rheumatoid arthritis patients expressed higher levels of CD40 and CD80 and lower levels of CD16, CD163, CD206, and CD200R after polarization, they also expressed higher CDKN2B-AS1, lower MIR497, and higher TXNIP. In macrophages from healthy donors, there was no correlation among CDKN2B-AS1, MIR497, and TXNIP. But in macrophages from patients, there were significant correlations. The CDKN2B-AS1 knockdown, MIR497 mimics suppressed the M1 polarization but promoted the M2 polarization in MD cells, while the MIR497 knockdown and the TXNIP overexpression did the opposite. This study demonstrated that elevated CDKN2B-AS1 in macrophages promotes the M1 polarization and inhibited the M2 polarization of macrophages by the CDKN2B-AS1/ MIR497/TXNIP axis. |