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ID PMID Title PublicationDate abstract
33625544 Does smoking affect level of seropositivity in RA? A post-HOC global and inter-country ana 2021 Apr To study the association of smoking status and the level of seropositivity in RA patients from COMORA Cohort. A post hoc analysis of COMORA database included 3439 RA patients was performed. Current smokers or recently quitted (< 3 years) were initially compared to those who never smoked or stopped > 3 years (Group I vs. II) regarding their seropositivity status (high positive, low positive and negative) for Rheumatoid Factor (RF) or Anti-citrullinated antibodies (ACPA). A further comparison was made between current smokers (Group III) and never smoked patients (Group IV). Analysis was also done on the individual country level for the 17 countries included in the COMORA study. Out of 3439 RA patients, 705 (20.5%) were smokers (group I), and 2734 (79.5%) were non-smokers (group II). Significantly more patients in group I, 442 (62.7%), had high levels of seropositivity than those in group II, 1556 (56.9%), [P = 0.006, OR 1.27 (95% CI, 1.07-1.5)]. More current smoker patients (group III-286 out of 456 "62.7%") had high levels of seropositivity than never smoked patients (group IV-1236 out of 2191 "56.4%"), with significant difference [P = 0.013, OR 1.3 (95% CI, 1.06-1.6)]. In 11 countries, higher proportions of patients with high level of seropositivity in group I was found, with statistical significance in four countries. Smoking was associated with higher level of seropositivity in patients with RA in this post hoc analysis, both on a global level and in certain individual countries. As smoking is a modifiable risk factor, studying the effects of quitting smoking on level of seropositivity and other disease parameters is warranted.
34081620 Development and validation of a nomogram for predicting stroke risk in rheumatoid arthriti 2021 Jun 3 We developed and validated a nomogram to predict the risk of stroke in patients with rheumatoid arthritis (RA) in northern China. Out of six machine learning algorithms studied to improve diagnostic and prognostic accuracy of the prediction model, the logistic regression algorithm showed high performance in terms of calibration and decision curve analysis. The nomogram included stratifications of sex, age, systolic blood pressure, C-reactive protein, erythrocyte sedimentation rate, total cholesterol, and low-density lipoprotein cholesterol along with the history of traditional risk factors such as hypertensive, diabetes, atrial fibrillation, and coronary heart disease. The nomogram exhibited a high Hosmer-Lemeshow goodness-for-fit and good calibration (P > 0.05). The analysis, including the area under the receiver operating characteristic curve, the net reclassification index, the integrated discrimination improvement, and clinical use, showed that our prediction model was more accurate than the Framingham risk model in predicting stroke risk in RA patients. In conclusion, the nomogram can be used for individualized preoperative prediction of stroke risk in RA patients.
34360594 Global Deletion of 11β-HSD1 Prevents Muscle Wasting Associated with Glucocorticoid Therap 2021 Jul 22 Glucocorticoids provide indispensable anti-inflammatory therapies. However, metabolic adverse effects including muscle wasting restrict their use. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) modulates peripheral glucocorticoid responses through pre-receptor metabolism. This study investigates how 11β-HSD1 influences skeletal muscle responses to glucocorticoid therapy for chronic inflammation. We assessed human skeletal muscle biopsies from patients with rheumatoid arthritis and osteoarthritis for 11β-HSD1 activity ex vivo. Using the TNF-α-transgenic mouse model (TNF-tg) of chronic inflammation, we examined the effects of corticosterone treatment and 11β-HSD1 global knock-out (11βKO) on skeletal muscle, measuring anti-inflammatory gene expression, muscle weights, fiber size distribution, and catabolic pathways. Muscle 11β-HSD1 activity was elevated in patients with rheumatoid arthritis and correlated with inflammation markers. In murine skeletal muscle, glucocorticoid administration suppressed IL6 expression in TNF-tg mice but not in TNF-tg(11βKO) mice. TNF-tg mice exhibited reductions in muscle weight and fiber size with glucocorticoid therapy. In contrast, TNF-tg(11βKO) mice were protected against glucocorticoid-induced muscle atrophy. Glucocorticoid-mediated activation of catabolic mediators (FoxO1, Trim63) was also diminished in TNF-tg(11βKO) compared to TNF-tg mice. In summary, 11β-HSD1 knock-out prevents muscle atrophy associated with glucocorticoid therapy in a model of chronic inflammation. Targeting 11β-HSD1 may offer a strategy to refine the safety of glucocorticoids.
33772624 Methotrexate-associated lymphoproliferative disorder of the thoracic spine in a patient wi 2021 Oct Methotrexate-associated lymphoproliferative disorder is recognized as a lymphoma that occurs following methotrexate administration. The lesion of the spine is extremely rare, and only one case of lesion in the lumbar spine has been reported so far. Here, we present a case of methotrexate-associated lymphoproliferative disorder of the thoracic spine in a 54-year-old woman with rheumatoid arthritis. The lesion formed an extra-skeletal tumor mass from lateral to the vertebral body to the paravertebral muscle extending posterior to the epidural space without bone destruction. Magnetic resonance imaging showed low signal intensities on both T1- and T2-weighted images and high signal intensity with short-tau inversion recovery. These radiological findings were similar to those for primary spinal lymphoma. The lesion rapidly paralyzed the patient, forcing her to be treated with posterior spinal decompression. The lesion could not be resected because it adhered to the dura. Following the histopathological diagnosis as methotrexate-associated lymphoproliferative disorder, methotrexate administration was terminated. The remaining mass lesion showed complete regression within 6 months. Methotrexate-associated lymphoproliferative disorder, which could be cured by the discontinuation of methotrexate, should be considered a differential diagnosis in spinal lesion cases showing lymphoma-like appearance with methotrexate treatment to avoid unnecessary treatments.
33555998 Enzyme-linked immunosorbent assays for monitoring TNF-alpha inhibitors and antibody levels 2021 Feb BACKGROUND: Rheumatoid arthritis is a chronic autoimmune disease that primarily causes inflammation, pain and stiffness in the joints. People with severe disease may be treated with biological disease-modifying anti-rheumatic drugs, including tumour necrosis factor-α inhibitors, but the efficacy of these drugs is hampered by the presence of anti-drug antibodies. Monitoring the response to these treatments typically involves clinical assessment using response criteria, such as Disease Activity Score in 28 joints or European League Against Rheumatism. Enzyme-linked immunosorbent assays can also be used to measure drug and antibody levels in the blood. These tests may inform whether or not adjustments to treatment are required or help clinicians to understand the reasons for treatment non-response or a loss of response. METHODS: Systematic reviews were conducted to identify studies reporting on the clinical effectiveness and cost-effectiveness of using enzyme-linked immunosorbent assays to measure drug and anti-drug antibody levels to monitor the response to tumour necrosis factor-α inhibitors [adalimumab (Humira(®); AbbVie, Inc., North Chicago, IL, USA), etanercept (Enbrel(®); Pfizer, Inc., New York, NY, USA), infliximab (Remicade(®), Merck Sharp & Dohme Limited, Hoddesdon, UK), certolizumab pegol (Cimzia(®); UCB Pharma Limited, Slough, UK) and golimumab (Simponi(®); Merck Sharp & Dohme Limited)] in people with rheumatoid arthritis who had either achieved treatment target (remission or low disease activity) or shown primary or secondary non-response to treatment. A range of bibliographic databases, including MEDLINE, EMBASE and CENTRAL (Cochrane Central Register of Controlled Trials), were searched from inception to November 2018. The risk of bias was assessed using the Cochrane ROBINS-1 (Risk Of Bias In Non-randomised Studies - of Interventions) tool for non-randomised studies, with adaptations as appropriate. Threshold and cost-utility analyses that were based on a decision tree model were conducted to estimate the economic outcomes of adding therapeutic drug monitoring to standard care. The costs and resource use were considered from the perspective of the NHS and Personal Social Services. No discounting was applied to the costs and effects owing to the short-term time horizon of 18 months that was adopted in the economic analysis. The impact on the results of variations in testing and treatment strategies was explored in numerous clinically plausible sensitivity analyses. RESULTS: Two studies were identified: (1) a non-randomised controlled trial, INGEBIO, that compared standard care with therapeutic drug monitoring using Promonitor(®) assays [Progenika Biopharma SA (a Grifols-Progenika company), Derio, Spain] in Spanish patients receiving adalimumab who had achieved remission or low disease activity; and (2) a historical control study. The economic analyses were informed by INGEBIO. Different outcomes from INGEBIO produced inconsistent results in both threshold and cost-utility analyses. The cost-effectiveness of therapeutic drug monitoring varied, from the intervention being dominant to the incremental cost-effectiveness ratio of £164,009 per quality-adjusted life-year gained. However, when the frequency of testing was assumed to be once per year and the cost of phlebotomy appointments was excluded, therapeutic drug monitoring dominated standard care. LIMITATIONS: There is limited relevant research evidence and much uncertainty about the clinical effectiveness and cost-effectiveness of using enzyme-linked immunosorbent assay-based testing for therapeutic drug monitoring in rheumatoid arthritis patients. INGEBIO had serious limitations in relation to the National Institute for Health and Care Excellence scope: only one-third of participants had rheumatoid arthritis, the analyses were mostly not by intention to treat and the follow-up was 18 months only. Moreover, the outcomes might not be generalisable to the NHS. CONCLUSIONS: Based on the available evidence, no firm conclusions could be made about the cost-effectiveness of therapeutic drug monitoring in England and Wales. FUTURE WORK: Further controlled trials are required to assess the impact of using enzyme-linked immunosorbent assays for monitoring the anti-tumour necrosis factors in people with rheumatoid arthritis. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018105195. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 8. See the NIHR Journals Library website for further project information.
32339483 A Systematic Review of the Incidence, Prevalence, Costs, and Activity and Work Limitations 2021 Jan OBJECTIVES: To present recent evidence on the prevalence, incidence, costs, activity limitations, and work limitations of common conditions requiring rehabilitation. DATA SOURCES: Medline (PubMed), SCOPUS, Web of Science, and the gray literature were searched for relevant articles about amputation, osteoarthritis, rheumatoid arthritis, back pain, multiple sclerosis, spinal cord injury, stroke, and traumatic brain injury. STUDY SELECTION: Relevant articles (N=106) were included. DATA EXTRACTION: Two investigators independently reviewed articles and selected relevant articles for inclusion. Quality grading was performed using the Methodological Evaluation of Observational Research Checklist and Newcastle-Ottawa Quality Assessment Form. DATA SYNTHESIS: The prevalence of back pain in the past 3 months was 33.9% among community-dwelling adults, and patients with back pain contribute $365 billion in all-cause medical costs. Osteoarthritis is the next most prevalent condition (approximately 10.4%), and patients with this condition contribute $460 billion in all-cause medical costs. These 2 conditions are the most prevalent and costly (medically) of the illnesses explored in this study. Stroke follows these conditions in both prevalence (2.5%-3.7%) and medical costs ($28 billion). Other conditions may have a lower prevalence but are associated with relatively higher per capita effects. CONCLUSIONS: Consistent with previous findings, back pain and osteoarthritis are the most prevalent conditions with high aggregate medical costs. By contrast, other conditions have a lower prevalence or cost but relatively higher per capita costs and effects on activity and work. The data are extremely heterogeneous, which makes anything beyond broad comparisons challenging. Additional information is needed to determine the relative impact of each condition.
35125800 Corneal Hysteresis, Central Corneal Thickness, and Intraocular Pressure in Rheumatoid Arth 2021 Jul PURPOSE: To evaluate biomechanical properties, corneal thickness, and intraocular pressure (IOP) in patients with rheumatoid arthritis (RA) and correlate them with rheumatoid activity. PATIENTS AND METHODS: Forty RA eyes were enrolled in a cross-sectional study. Clinical Disease Activity Index (CDAI) was used to assess the rheumatoid activity by a rheumatologist. Corneal hysteresis (CH), corneal resistance factor (CRF), and IOP corneal compensated, IOP Goldmann corrected were assessed using ocular response analyzer (ORA), Corneal thickness was measured using optical coherence tomography, and IOP using Goldman applanation tonometer (IOP GAT). RESULTS: There was a positive correlation between CH and CRF (P < 0.001 and r = 0.818) and (P < 0.001 and r = 0.714) in the active and inactive groups respectively, also between CRF and central corneal thickness (CCT) (P value 0.05 and r = 0.0435) in Inactive Group only. No correlation was found between CDAI score and ORA parameters. There was a negative correlation between CDAI and CCT in Active Group only (P < 0.001 and r = -0.823). CONCLUSION: Corneal biomechanical properties could be affected in rheumatoid patients in both active and remission phases, which may indicate that any corneal changes may be irreversible. These changes are of important significance regarding IOP measurement in rheumatoid patients. CCT may be a new parameter in the follow up of disease activity.
33587021 Amelioration of rheumatoid arthritis in a breast cancer patient treated with palbociclib: 2021 Jul Rheumatoid arthritis is a common autoimmune disease that requires new therapeutic agents. Cyclin-dependent kinase 4/6 inhibitors have recently been approved for metastatic breast cancer patients and have also been reported to improve the arthritis score in collagen-induced arthritis mouse models. We report a 56-year-old woman who had previously been diagnosed with rheumatoid arthritis and treated with methotrexate. At age 40, she underwent surgery with curative intent for breast cancer but subsequently developed lung metastases. Palbociclib, a cyclin-dependent kinase 4/6 inhibitor, was administered in combination with fulvestrant (anti-oestrogen drug) for metastatic breast cancer. One month later, serum matrix metalloproteinase-3 and C-reactive protein levels were markedly decreased, and her rheumatoid arthritis symptoms, which had worsened just prior to the detection of metastatic lung disease, showed amelioration. Methotrexate, which had been used to treat her rheumatoid arthritis, could subsequently be administered in a reduced dose. The cyclin-dependent kinase 4/6 inhibitor was also effective for the metastatic breast cancer, and, to date, the patient's disease has remained stable for more than one year. Based on the results of basic research, cyclin-dependent kinase 4/6 inhibitors are promising new therapeutic agents for rheumatoid arthritis patients, although these drugs have not, as yet, been used in a clinical setting. To the best of our knowledge, this is the first report to describe a patient whose rheumatoid arthritis responded to a cyclin-dependent kinase 4/6 inhibitor administered for metastatic breast cancer.
34242246 Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthriti 2021 The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteristics is shedding of syndecan-1 from endothelial cells. Syndecan-1 shedding is mediated by matrix metalloproteinase-9 (MMP-9) and counteracted by tissue inhibitor of metalloproteinases (TIMP)-1. Cardiovascular disease risk in RA is reversible by disease modifying antirheumatic drugs (DMARDs), but the exact modes of action are still unclear. Therefore, we examined effects of DMARDs on syndecan-1, MMP-9 and TIMP-1 in RA patients, and searched for associations between these parameters and inflammatory activity. From the observational PSARA study, we examined 39 patients starting with methotrexate (MTX) monotherapy (in MTX naïve patients, n = 19) or tumor necrosis factor inhibitors (TNFi) in combination with MTX (in MTX non-responders, n = 20) due to active RA. Serum syndecan-1, MMP-9 and TIMP-1 were measured at baseline and after six weeks of treatment. Serum syndecan-1 (p = 0.008) and TIMP-1 (p<0.001) levels decreased after six weeks of anti-rheumatic treatment. Levels of MMP-9 also decreased, but the difference was not statistically significant. The improvement in syndecan-1 levels were independent of changes in inflammatory activity. There was no significant difference in changes in syndecan-1 levels from baseline to 6 weeks between the MTX and TNFi groups, however the change was significant within the MTX group. Six weeks of antirheumatic treatment was associated with reduction in serum levels of syndecan-1, which might reflect reduced syndecan-1 shedding from EG. Thus, it is possible that EG-preserving properties of DMARDs might contribute to their cardioprotective effects. These effects may be at least partly independent of their anti-inflammatory actions. Our findings do not support the notion that syndecan-1 shedding in RA is mediated mainly by increased MMP-9 or decreased TIMP-9 serum concentration.
32374918 Real-World Outcomes Associated With Methotrexate, Sulfasalazine, and Hydroxychloroquine Tr 2021 Aug OBJECTIVE: Though randomized controlled trials have demonstrated relatively comparable clinical outcomes with triple therapy (methotrexate [MTX], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) compared to combination therapy (tumor necrosis factor inhibitor [TNFi] and MTX), real-world experiences comparing these strategies have not been well studied. METHODS: We evaluated the clinical effectiveness and effects of medication discontinuation of triple therapy with MTX/SSZ/HCQ versus combination therapy with TNFi/MTX in rheumatoid arthritis (RA) patients enrolled in the Corrona RA Drug Safety & Effectiveness Registry. Propensity score matching was used to match patients up to a ratio of 1:3 to adjust for imbalances between treatment groups, with stratification performed according to biologics-naive or biologics-exposed status of study participants. RESULTS: Patients eligible for analysis in this study included biologics-naive RA patients (3,926 who received combination therapy with TNFi/MTX and 262 who received triple therapy with MTX/SSZ/HCQ) and biologics-exposed RA patients (3,365 who received combination therapy with TNFi/MTX and 130 patients who received triple therapy with MTX/SSZ/HCQ). Before propensity score matching, numerous factors were imbalanced between the treatment groups, with triple therapy patients generally being older, having a longer disease duration of RA and lower RA disease activity, and more likely having a history of malignancy and other comorbidities. After matching, almost all (93-98%) triple therapy patients could be matched to TNFi/MTX therapy patients, and cohort characteristics were generally well balanced. Discontinuation of medication was greater in triple therapy patients referent to TNFi/MTX therapy patients (adjusted hazard ratio [HR] of 2.17 [95% confidence interval 1.63-2.88] in the biologics-naive group; adjusted HR of 1.51 [95% confidence interval 1.06-2.15] in the biologics-exposed group). At 6 months, the proportion of biologics-naive patients attaining low disease activity was significantly greater in the TNFi/MTX treatment group (49.2% in TNFi/MTX therapy patients versus 33.3% in triple therapy patients), as was the mean change in Clinical Disease Activity Index scores (-9.3 units versus -5.5 [95% confidence interval -1.5, -6.1]). Corresponding results in the biologics-exposed patients numerically favored TNFi/MTX therapy compared to triple therapy but did not reach statistical significance. CONCLUSION: Few patients receive triple therapy with MTX/SSZ/HCQ in the US. In the present study, drug persistence and clinical effectiveness outcomes were less favorable in triple therapy patients compared to TNFi/MTX therapy patients.
32541071 Higher Prevalence and Degree of Insulin Resistance in Patients With Rheumatoid Arthritis T 2021 Mar OBJECTIVE: Since insulin resistance (IR) is highly prevalent in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), we aimed to determine whether differences in IR exist between the two conditions. METHODS: We conducted a cross-sectional study comprising 413 subjects without diabetes (186 with SLE and 227 with RA). Glucose, insulin, and C-peptide serum levels, as well as IR by the homeostatic model assessment (HOMA2) were studied. A multivariable regression analysis was performed to evaluate the differences in IR indexes between patients with SLE and RA, as well as to determine if IR risk factors or disease-related characteristics are differentially associated with IR in both populations. RESULTS: The insulin:C-peptide molar ratio was upregulated in patients with RA compared to patients with SLE (β 0.009, 95% CI 0.005-0.014, P < 0.001) after multivariable analysis. HOMA2 indexes related to insulin sensitivity (HOMA2-%S) were found to be lower (β -27, 95% CI -46 to -9, P = 0.004) and β cell function (HOMA2-%B) showed higher IR indexes (β 38, 95% CI 23-52, P < 0.001) in RA than in SLE patients after multivariable analysis. Patients with RA more often fulfilled the definition of IR than those with SLE (OR 2.15, 95% CI 1.25-3.69, P = 0.005). The size effect of IR factors on IR indexes was found to be equal in both diseases. CONCLUSION: IR sensitivity is lower and β cell function is higher in RA than in SLE patients. The fact that traditional IR factors have an equal effect on IR in both SLE and RA supports the contention that these differences are related to the diseases themselves.
33089506 Screening of dental and sinus infections in rheumatoid arthritis. 2021 Apr BACKGROUND: Rheumatoid arthritis (RA) is associated with increased risk of infections. Screening for oral (dental and/or sinus) infection could be proposed before biologic disease-modifying antirheumatic drugs (bDMARDs) initiation but is not systematically recommended. The aim of our study was to assess the prevalence of oral infection in RA patients requiring bDMARDs. MATERIALS AND METHODS: This was a monocentric retrospective study. We included patients with RA and active disease requiring bDMARDs. Dental infection and sinusitis were assessed by a stomatologist and otorhinolaryngologist after clinical, panoramic dental X-ray and sinus CT evaluation. Factors associated with oral infections were analysed in uni- and multivariate models, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 223 RA patients (79.4% women, mean disease duration 8.9 ± 8.6 years). The mean age was 54.4 ± 10.9 years and mean Disease Activity Score in 28 joints 5.5 ± 2.6. Systematic dental screening revealed infection requiring treatment before bDMARDs initiation in 46 (20.9%) patients. Sinusitis was diagnosed by the otorhinolaryngologist in 33 (14.8%) patients. Among the 223 patients, 69 (30.9%) had dental and/or sinus infection. On univariate analysis, active smoking was associated with increased probability of oral infection (OR = 2.16 [95% CI 1.02-4.57], P = .038) and methotrexate with reduced probability (OR = 0.43 [95% CI 0.23-0.81], P = .006). On multivariate analysis, no RA variables were associated with oral infection. CONCLUSION: In our study, asymptomatic oral infection was confirmed in one third of RA patients.
34480694 Inflammatory macrophages exacerbate neutrophil-driven joint damage through ADP/P2Y(1) sign 2022 May Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints and is associated with excessive immune cell infiltration. However, the complex interactions between the immune cell populations in the RA synovium remain unknown. Here, we demonstrate that inflammatory macrophages in the synovium exacerbate neutrophil-driven joint damage in RA through ADP/P2Y(1) signaling. We show that extracellular ADP (eADP) and its receptors are obviously increased in synovial tissues of RA patients as well as collagen-induced arthritis (CIA) mice, and eADP enhances neutrophil infiltration into joints through macrophages producing the chemokine CXCL2, aggravating disease development. Accordingly, the arthritis mouse model had more neutrophils in inflamed joints following ADP injection, whereas P2Y(1) deficiency and pharmacologic inhibition restored arthritis severity to basal levels, suggesting a dominant role of ADP/P2Y(1) signaling in RA pathology. Moreover, cellular activity of ADP/P2Y(1)-mediated CXCL2 production was dependent on the G(αq)/Ca(2+)-NF-κB/NFAT pathway in macrophages. Overall, this study reveals a non-redundant role of eADP as a trigger in the pathogenesis of RA through neutrophil recruitment and disrupted tissue homeostasis and function.
34360736 Regulatory Macrophages and Tolerogenic Dendritic Cells in Myeloid Regulatory Cell-Based Th 2021 Jul 26 Myeloid regulatory cell-based therapy has been shown to be a promising cell-based medicinal approach in organ transplantation and for the treatment of autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, Crohn's disease and multiple sclerosis. Dendritic cells (DCs) are the most efficient antigen-presenting cells and can naturally acquire tolerogenic properties through a variety of differentiation signals and stimuli. Several subtypes of DCs have been generated using additional agents, including vitamin D3, rapamycin and dexamethasone, or immunosuppressive cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). These cells have been extensively studied in animals and humans to develop clinical-grade tolerogenic (tol)DCs. Regulatory macrophages (Mregs) are another type of protective myeloid cell that provide a tolerogenic environment, and have mainly been studied within the context of research on organ transplantation. This review aims to thoroughly describe the ex vivo generation of tolDCs and Mregs, their mechanism of action, as well as their therapeutic application and assessment in human clinical trials.
34011040 Efficacy of Bi Qi Capsules in combination with methotrexate in the treatment of rheumatoid 2021 May 21 BACKGROUND: It is known that Bi Qi Capsules (BQC) have synergistic effects when combined with Methotrexate, but there is a lack of clinical studies on the long-term efficacy and safety of the combination of the 2 in the treatment of rheumatoid arthritis (RA). Therefore, the purpose of this randomized controlled trial was to evaluate the long-term efficacy and safety of this treatment. METHODS: This was a prospective, double-blind, single-simulation, randomized controlled trial investigating the efficacy and safety of BQC in combination with Methotrexate in the treatment of RA, and was approved by the Clinical Research Ethics Committee of the hospital. Patients were randomized in a 1:1 ratio to either the observation or control group and were respectively followed up for 6 months after receiving 12 weeks of treatment. The observation indexes included: total effective rate, DAS-28 score, inflammatory indexes, and adverse reactions. Finally, the collected data was statistically analyzed by SPSS version 18.0. DISCUSSION: This study evaluated the long-term efficacy of BQC in combination with Methotrexate in the treatment of RA. The trial results of this study will provide new ideas for choosing a combination of Chinese and Western medicine protocols for the treatment of RA. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/U85GX.
34449990 Methotrexate-Induced Cutaneous Ulcers: A Rare Side Effect. 2021 Jul Methotrexate is often prescribed for the treatment of autoimmune conditions. There are many well-known side effects of methotrexate, a lesser known side effect is methotrexate-induced cutaneous ulceration. Only eight cases have been reported in the literature. Here we report a ninth case report of methotrexate-induced cutaneous ulceration in a 73-year-old female who had recently had her methotrexate dose increased for her seronegative rheumatoid arthritis. She presented to the emergency department with painful ulcerative nodules on her hands. In addition, laboratory evaluation found her to be pancytopenic. Methotrexate was discontinued and patient was given a dose of leucovorin. Within a couple weeks of methotrexate discontinuation, the ulcers resolved. Our case in addition to a review of the literature suggests that methotrexate-induced cutaneous ulceration may be an indication of life-threatening pancytopenia.
33679725 Serum Amyloid A in Inflammatory Rheumatic Diseases: A Compendious Review of a Renowned Bio 2020 Serum amyloid A (SAA) is an acute phase protein with a significant importance for patients with inflammatory rheumatic diseases (IRD). The central role of SAA in pathogenesis of IRD has been confirmed by recent discoveries, including its involvement in the activation of the inflammasome cascade and recruitment of interleukin 17 producing T helper cells. Clinical utility of SAA in IRD was originally evaluated nearly half a century ago. From the first findings, it was clear that SAA could be used for evaluating disease severity and monitoring disease activity in patients with rheumatoid arthritis and secondary amyloidosis. However, cost-effective and more easily applicable markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), overwhelmed its use in clinical practice. In the light of emerging evidences, SAA has been discerned as a more sensitive biomarker in a wide spectrum of IRD, especially in case of subclinical inflammation. Furthermore, a growing number of studies are confirming the advantages of SAA over many other biomarkers in predicting and monitoring response to biological immunotherapy in IRD patients. Arising scientific discoveries regarding the role of SAA, as well as delineating SAA and its isoforms as the most sensitive biomarkers in various IRD by recently developing proteomic techniques are encouraging the revival of its clinical use. Finally, the most recent findings have shown that SAA is a biomarker of severe Coronavirus disease 2019 (COVID-19). The aim of this review is to discuss the SAA-involving immune system network with emphasis on mechanisms relevant for IRD, as well as usefulness of SAA as a biomarker in various IRD. Therefore, over a hundred original papers were collected through an extensive PubMed and Scopus databases search. These recently arising insights will hopefully lead to a better management of IRD patients and might even inspire the development of new therapeutic strategies with SAA as a target.
33723242 Protectin DX restores Treg/T(h)17 cell balance in rheumatoid arthritis by inhibiting NLRP3 2021 Mar 15 Regulatory T-cell (Treg)/T-helper 17 (T(h)17) cell balance plays an important role in the progression of rheumatoid arthritis (RA). Our study explored the protective effect of protectin DX (PDX), which restored Treg/T(h)17 cell balance in RA, and the role of the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome pathway in this process. Using mass spectrometry, we discovered that level of PDX decreased in active-RA patients and increased in inactive-RA patients compared with HCs, and serum PDX was a potential biomarker in RA activity detection (area under the curve [AUC] = 0.86). In addition, a collagen-induced arthritis (CIA) mice model was constructed and PDX obviously delayed RA progression in the CIA model, upregulating Tregs and anti-inflammatory cytokines while downregulating T(h)17 cells and pro-inflammatory cytokines. Moreover, NLRP3 knockout and rescue experiments demonstrated that NLRP3 participated in PDX-mediated Treg/T(h)17 cell balance restoration, joint injury amelioration and inflammatory-response attenuation using Nlrp3(-/-) mice. Furthermore, microarray and verified experiments confirmed that PDX reduced NLRP3 expression via miRNA-20a (miR-20a). In summary, we confirmed for the first time that PDX could effectively ameliorate CIA progression by restoring Treg/T(h)17 cell balance, which was mediated by inhibition of the NLRP3 inflammasome pathway via miR-20a.
33754936 Coexistent subclinical hypothyroidism is associated with an increased risk of new cardiova 2021 Nov Objective: Autoimmune thyroid disease often coexists with rheumatoid arthritis (RA) and is associated with elevated cardiovascular (CV) risk. However, studies in RA patients are scarce. Our aim was to investigate whether autoimmune thyroid disease increases the risk of new cardiovascular disease (CVD) in RA.Method: Thyroid-stimulating hormone (TSH) and serum free thyroxine (FT4) were assessed in 323 RA patients participating in an ongoing prospective cohort study designed to assess CV risk factors, morbidity, and mortality. Cox proportional hazard models were used to calculate hazard ratios (HRs) for new CVD and adjusted for age, gender, smoking, prevalent CVD, thyroxine replacement therapy, and RA duration.Results: Of the 323 participants, 65.3% were female, and mean ± sd age was 63 ± 7 years. At baseline, 8.1% were hypothyroid (n = 26, 16 clinical, 10 subclinical), 6.8% hyperthyroid (n = 22, 13 clinical, 9 subclinical), and 85.1% (n = 275) euthyroid. A new CV event developed in 94 patients (29.1%) during follow-up. Compared to euthyroid patients, the HR adjusted for age, gender, and prevalent CVD was 2.83 [95% confidence interval (CI) 1.13-7.09; p = 0.026] for subclinical hypothyroidism. Further adjustment for smoking, thyroxine replacement therapy, and RA duration resulted in an HR of 3.0 (95% CI 1.19-7.54; p = 0.02) for CV events in patients with subclinical hypothyroidism.Conclusion: There was no difference in CVD between RA patients with hypothyroidism and hyperthyroidism versus euthyroid patients. Coexistence of subclinical hypothyroidism with RA is associated with a higher occurrence of new CV events. Treatment trials are needed to determine whether thyroxine supplementation can further improve CV outcome in these patients.
34362290 Emerging role of leptin in joint inflammation and destruction. 2022 Mar Rheumatoid arthritis (RA) is an autoimmune disease characterized by tumor-like hyperplasia and inflammation of the synovium, which causes synovial cell invasion into the bone and cartilage. In RA pathogenesis, various molecules in effector cells (i.e., immune cells and mesenchymal cells) are dysregulated by genetic and environmental factors. Consistent with the early stages of RA, these pathogenic cells cooperate and activate each other directly by cell-to-cell contact or indirectly via humoral factors. Recently, growing evidence has revealed essential role of adipokines, which are multifunctional signal transduction molecules, in the immune system. In this review, we summarize the current understanding of the cross-talk between leptin, one of the most well-known and best-characterized adipokines, and osteoimmunology. Furthermore, we discuss the contribution of leptin to the pathogenesis of RA and its potential mechanisms.