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ID PMID Title PublicationDate abstract
32990844 MiR-130a/Ndrg2 Axis Inhibits the Proliferation of Fibroblast-Like Synoviocytes in Rheumato 2020 Dec Studies have found that N-myc downstream-regulated gene 2 (Ndrg2) is involved in the progression of rheumatoid arthritis (RA); however, the specific mechanism still remains unclear. Gene expression profiles in the tibial joints of the collagen-induced rheumatoid arthritis model were obtained using Gene Expression Omnibus database. Western blot and real-time PCR were respectively performed to determine the expression of Ndrg2 and gene messenger RNA. Cell viability was measured by Cell Counting Kit-8 (CCK-8) method, and cell cycle was detected by flow cytometry. Cell scratch assays were carried out to detect migration. The binding ability of miR-130a to Ndrg2-3'-UTR was predicted by TargetScan website and confirmed by dual luciferase assay. A collagen-induced arthritis rat model was constructed to observe the effects of miR-130a on arthritis index, hind limb swelling, volume of rat hind paw, and inflammation. Ndrg2 was found downregulated in RA tissues, and knockdown of Ndrg2 promoted fibroblast-like synoviocytes (FLS) proliferation and inflammation, while overexpressed Ndrg2 produced opposite results. Ndrg2 was predicted as a target gene for miR-130a, and miR-130a mimic promoted FLS proliferation, while miR-130a inhibitor suppressed FLS proliferation. Moreover, we found that miR-130a antagomir could significantly reduce the arthritis index, swelling degree, foot volume, and inflammatory factor levels; inhibit the expression of miR-130a; and promote the expression of Ndrg2. The miR-130a/Ndrg2 axis signaling pathway is involved in the progression of RA. Our findings provide a theoretical basis for the clinical treatment of RA.
31969526 Efficacy and Safety of Targeted Strategy for Treating Rheumatoid Arthritis Patients Aged 7 2020 Jan The efficacy and safety of targeted treatment for elderly patients with rheumatoid arthritis (RA) was considered. Patients with RA who met the ACR/EULAR 2010 classification criteria and were treated consecutively for > 3 years, were recruited and classified into three age groups with 10-year increments from 65 years. Treatment protocol that aims to achieve clinical remission within 6 months was commonly adopted. The salient features are the rapid increase in dosages of conventional synthetic anti-rheumatic drugs (csDMARDs) and the administration of need-based concomitant biologic/targeted synthetic drugs and/or glucocorticoid steroid, and immediate tapering of glucocorticoid steroid and csDMARDs is required on attaining clinical remission. Disease activity score and other clinical indices specific for RA treatment, and the prevalence of adverse events were compared between the groups. The numbers of patients in the groups of the < 65 years, 65-74 years, and ≥ 75 years were 269, 155, and 152. No significant difference was observed between any pairs of groups with respect to disease activity; stable course after achievement of minimum disease activity was observed in all groups. However, the prevalence of adverse events, especially serious infection, in the oldest group was higher than that in the younger groups, which was likely attributable to the higher frequency of administration of glucocorticoid steroid after minimum disease activity obtained and higher prevalence of cardiovascular comorbidities. Targeted treatment is feasible even for patients aged ≥ 75. However, glucocorticoid steroid administration is considered as a risk of adverse events and should be tapered immediately.
33243729 [Mechanism of Xiaowugui decoction for treating collagen-induced arthritis in mice]. 2020 Nov 30 OBJECTIVE: To explore the mechanism of Xiaowugui decoction (XWGD) decoction in treating rheumatoid arthritis (RA) in mice. METHODS: Healthy male DBA/1 mice were used for CIA modeling. Twenty-five CIA mice with successful modeling and similar arthritis index (AI) scores were randomized equally into model group (CIA), methotrexate (MTX) group, and low-, medium-, and high-dose XWGD groups (0.975, 1.95, and 3.9 g/mL, respectively), with another 5 normal mice as the normal control group. The mice in normal control and CIA groups were given saline once a day, those in MTX group were given 0.1 mg/mL MTX once a week, and those in XWGD groups were treated daily via garage of XWGD containing crude drugs of different doses for 28 consecutive days. The AI score and HE staining were used to evaluate the changes in the joints of the CIA mice. The effect of XWGD on Th1, Th17, MDSC, G-MDSC and M-MDSC cells were evaluated with flow cytometry. RESULTS: Treatment with MTX and different doses of XWGD significantly decreased the AI score of the mice and relieved joint inflammation as compared with the model group (P < 0.05), and a higher dose of XWGD decoction produced a stronger therapeutic effect. Compared with those in CIA model group, the mice in MTX and XWGD treatment groups showed significantly decreased percentages of Th1, Th17 and M-MDSC cells in the spleen and increased percentages of G-MDSC cells (P < 0.01), and these changes were more conspicuous with a higher dose of XWGD. Correlation analysis showed that Th1 and Th17 cells were positively correlated with M-MDSC and negatively correlated with G-MDSC cells (P < 0.01). CONCLUSIONS: XWGD can improve joint inflammation in CIA mice by increasing the percentages of G-MDSC cells and decreasing the percentages of M-MDSC, Th1 and Th17 cells, and a high dose of XWGD can produce an equivalent therapeutic effect to methotrexate but with better safety.
31203222 Correlates of Successful Rheumatoid Arthritis Flare Management: Clinician-driven Treatment 2020 Mar OBJECTIVE: Describe strategies used to manage rheumatoid arthritis (RA) flares that contribute to a successful postflare outcome. METHODS: Data were collected from the BRASS registry, including clinical and patient-reported outcomes, and a survey with a Likert scale assessing postflare symptoms (better, unchanged, or worse). A logistic regression analysis adjusting for age, sex, flare number in the past 6 months, flare pain severity, home management, clinical consultation, and medication change was performed to evaluate factors influencing flare outcome. RESULTS: Of 503 participants, 185 reported at least 1 flare that had resolved in the past 6 months, with median (interquartile range) 28-joint count Disease Activity Score based on C-reactive protein 3 score 2.1 (1.7-2.8). Compared with RA symptoms before the flare, 22 (12%) patients felt worse, 125 (68%) were unchanged, and 38 (20%) felt better. To manage flares, 72% of patients used home-based remedies, 23% sought clinical consultation, and 56% made medication change. Of 103 patients who changed medication, 70% did so without seeking clinical advice. Making a medication change (OR 3.48, 95% CI 1.68-7.21) and having lower flare pain (OR 0.83, 95% CI 0.71-0.97) were associated with better flare outcome. CONCLUSION: Flares occur frequently even in patients with low disease activity. Independent of home-based or clinically guided care, making a medication change and having less severe pain during a flare were associated with better flare outcomes. Of interest, the decision to change medications was frequently made without clinical advice. Future studies might address how best to intervene when patients experience flares and whether patient-initiated medication changes have adverse outcomes.
32863415 Methotrexate-Induced Pancytopenia and Mucositis Caused by Medication Error. 2020 Mar The use of methotrexate in routine clinical practice is becoming more common among specialties such as rheumatology, dermatology, oncology and obstetrics. General clinicians are increasingly encountering patients on this drug. Though it has a high safety profile, there is a recognised risk of acute toxicity or long-term complications associated with its use, which can be worsened by several factors such as advanced age, moderate to severe renal impairment, low folate level and/or inadequate folate supplementation, hypoalbuminaemia, polypharmacy causing drug-drug interactions and wrongful administration. We present a case of a 45-year old woman with rheumatoid arthritis who presented with acute pancytopaenia and mucositis due to methotrexate toxicity. We highlight its peculiar dosing regimen to minimise prescribing errors. FUNDING: None.
32275961 Reconstruction and repair of atraumatic extensor tendon ruptures in rheumatoid wrists: Les 2020 Sep The purpose of this study was to investigate the outcomes of extensor tendon repair involving the original stump in atraumatic extensor tendon rupture of rheumatoid wrists. For this study, 16 cases were reviewed involving 14 patients with rheumatoid arthritis. A total of 52 ruptured tendons impacted 36 fingers; 51 tendons were repaired in 35 fingers. The ruptured tendon stumps were repaired either directly by end-to-end suture or by free interposition tendon graft. The 8- to 10-strand core suture method was used for direct repair with a looped 4-0 nylon suture. In all patients, the extensor retinaculum was released and repaired under the tendons. Postoperatively, a volar splint with the wrist and fingers extended was applied for 3 to 4 weeks, followed by a removable splint and gentle active flexion until 6 weeks. The mean follow-up period was 32 months. All fingers recovered active metacarpophalangeal (MCP) joint extension, including independent and active extension of the little finger. Overall, the mean extension lag at the MCP joint was 1.7°. The mean fingertip-to-palm distance with the MCP joint flexed was 0.24mm. The mean extension lag at the MCP joint was significantly greater after interposition tendon grafting (3.2°) than after direct repair (0°). There was no significant difference in the mean fingertip-to-palm distance between direct repair (0.38mm) and interposition tendon grafting (0.13mm). No re-rupture or additional extensor tendon rupture was observed. Repair of the original extensor tendon stump yields satisfactory outcomes and appears to be a viable alternative to tendon transfers in patients with rheumatoid wrists with atraumatic extensor tendon ruptures. Direct repair reduces postoperative extension lag without a significant difference in flexion deficit when compared with interposition tendon grafting.
32120309 Horseshoe abscess of the hand with rice bodies secondary to mycobacterium avium intracellu 2020 Jul A horseshoe abscess is caused by infection that spreads between the flexor tendon sheath of the thumb or little finger through the radial and ulnar bursae through communication between the two and/or the space of Parona. We present a case of an 80-year-old woman with rheumatoid arthritis who presented with 6 months of right hand and wrist soft tissue swelling, initially treated as a rheumatoid arthritis flare. MRI demonstrates the horseshoe abscess and after surgical irrigation and debridement with synovectomy, cultures demonstrated infection with mycobacterium avium intracellulare (MAI). This case demonstrates the importance of MRI in diagnosing and evaluating the extent of hand infections and for considering mycobacterial organisms for appropriate treatment and antibiotic regimen.
32924689 The impact of coexisting fibromyalgia syndrome on disease activity in patients with psoria 2021 Jul BACKGROUND/OBJECTIVE: This study aims to assess the coexistence of fibromyalgia syndrome (FMS) and impact of possible FMS on disease activity in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: A total of 126 patients, aged 18-65 years old, who were being followed up with PsA (n = 64) and RA (n = 62) diagnoses were included. The Fibromyalgia Rapid Screening Tool (FiRST) was administered for screening FMS. Patients were divided according to the presence of FMS; PsA patients with FMS, patients with PsA without FMS, patients with both RA and FMS and patients with RA without FMS. Disease Activity Score 28 (DAS28) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were recorded. RESULTS: FMS was detected in 26.5% of the patients with PsA and 17.7% of the patients with RA (p = .04). A statistically significant higher DAS28 and BASDAI scores were found in patients with FMS (p < .05). There was statistically significant correlation between FiRST with DAS28 and BASDAI scores (p < .001, p = .03, respectively) in PsA patients. No significant correlation was found between FiRST score with age, disease duration, CRP and DAS28 in patients with RA (p > .05). CONCLUSION: The patients with concomitant FMS had higher disease activity parameters (DAS28 and BASDAI) than those without FMS.
32857281 Cardiovascular risk assessment in patients with rheumatoid arthritis using carotid ultraso 2020 Dec Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease that affects synovial joints and has various extra-articular manifestations, including atherosclerotic cardiovascular disease (CVD). Patients with RA experience a higher risk of CVD, leading to increased morbidity and mortality. Inflammation is a common phenomenon in RA and CVD. The pathophysiological association between these diseases is still not clear, and, thus, the risk assessment and detection of CVD in such patients is of clinical importance. Recently, artificial intelligence (AI) has gained prominence in advancing healthcare and, therefore, may further help to investigate the RA-CVD association. There are three aims of this review: (1) to summarize the three pathophysiological pathways that link RA to CVD; (2) to identify several traditional and carotid ultrasound image-based CVD risk calculators useful for RA patients, and (3) to understand the role of artificial intelligence in CVD risk assessment in RA patients. Our search strategy involves extensively searches in PubMed and Web of Science databases using search terms associated with CVD risk assessment in RA patients. A total of 120 peer-reviewed articles were screened for this review. We conclude that (a) two of the three pathways directly affect the atherosclerotic process, leading to heart injury, (b) carotid ultrasound image-based calculators have shown superior performance compared with conventional calculators, and (c) AI-based technologies in CVD risk assessment in RA patients are aggressively being adapted for routine practice of RA patients.
32472303 Measurement of sedentary time and physical activity in rheumatoid arthritis: an ActiGraph 2020 Sep Accurate measurement of sedentary time and physical activity (PA) is essential to establish their relationships with rheumatoid arthritis (RA) outcomes. Study objectives were to: (1) validate the GT3X+ and activPAL3(μ)™, and develop RA-specific accelerometer (count-based) cut-points for measuring sedentary time, light-intensity PA and moderate-intensity PA (laboratory-validation); (2) determine the accuracy of the RA-specific (vs. non-RA) cut-points, for estimating free-living sedentary time in RA (field-validation). Laboratory-validation: RA patients (n = 22) were fitted with a GT3X+, activPAL3(μ)™ and indirect calorimeter. Whilst being video-recorded, participants undertook 11 activities, comprising sedentary, light-intensity and moderate-intensity behaviours. Criterion standards for devices were indirect calorimetry (GT3X+) and direct observation (activPAL3(μ)™). Field-validation: RA patients (n = 100) wore a GT3X+ and activPAL3(μ)™ for 7 days. The criterion standard for sedentary time cut-points (RA-specific vs. non-RA) was the activPAL3(μ)™. Results of the laboratory-validation: GT3X-receiver operating characteristic curves generated RA-specific cut-points (counts/min) for: sedentary time = ≤ 244; light-intensity PA = 245-2501; moderate-intensity PA ≥ 2502 (all sensitivity ≥ 0.87 and 1-specificity ≤ 0.11). ActivPAL3(μ)™-Bland-Altman 95% limits of agreement (lower-upper [min]) were: sedentary = (- 0.1 to 0.2); standing = (- 0.7 to 1.1); stepping = (- 1.2 to 0.6). Results of the field-validation: compared to the activPAL3(μ)™, Bland-Altman 95% limits of agreement (lower-upper) for sedentary time (min/day) estimated by the RA-specific cut-point = (- 42.6 to 318.0) vs. the non-RA cut-point = (- 19.6 to 432.0). In conclusion, the activPAL3(μ)™ accurately quantifies sedentary, standing and stepping time in RA. The RA-specific cut-points offer a validated measure of sedentary time, light-intensity PA and moderate-intensity PA in these patients, and demonstrated superior accuracy for estimating free-living sedentary time, compared to non-RA cut-points.
31881419 Bulk and single cell transcriptomic data indicate that a dichotomy between inflammatory pa 2020 Mar BACKGROUND: Unbiased studies using different genome-wide methods have identified several novel biomarkers for diagnosis and treatment response in Rheumatoid Arthritis (RA). However, clinical translation has proven difficult. Here, we hypothesized that one reason could be that inflammatory responses in peripheral blood are different from those in the arthritic joint. METHODS: We performed meta-analysis of gene expression microarray data from synovium, whole blood cells (WBC), peripheral blood mononuclear cells (PBMC), and CD4+ T cells from patients with RA and healthy controls in order to identify overlapping pathways, upstream regulators and potential biomarkers. We also analyzed single cell RNA-sequencing (scRNA-seq) data from peripheral blood and whole joints from a mouse model of antigen-induced arthritis. RESULTS: Analyses of two profiling data sets from synovium from RA patients and healthy controls all showed significant activation of pathways with known pathogenic relevance, such as the Th1 pathway, the role of NFAT in regulation of the immune response, dendritic cell maturation, iCOS-iCOSL signaling in T helper cells, Fcγ receptor-mediated phagocytosis, interferon signaling, Cdc42 signaling, and cytotoxic T lymphocyte-mediated apoptosis. The most activated upstream regulators included TNF, an important drug target, as well as IFN-gamma and CD40LG, all of which are known to play important pathogenic roles in RA. The differentially expressed genes from synovium included several potential biomarkers, such as CCL5, CCL13, CCL18, CX3CL1, CXCL6, CXCL9, CXCL10, CXCL13, IL15, IL32, IL1RN, SPP1, and TNFSF11. By contrast, microarray studies of WBC, PBMC and CD4+ T cells showed variable pathways and limited pathway overlap with synovium. Similarly, scRNA-seq data from a mouse model of arthritis did not support that inflammatory responses in peripheral blood reflect those in the arthritic joints. These data showed pathway overlap between mouse joint cells and synovium from patients with RA, but not with cells in peripheral blood. CONCLUSIONS: Our findings indicate a dichotomy between gene expression changes, pathways, upstream regulators and biomarkers in synovium and cell types in peripheral blood, which complicates identification of biomarkers in blood.
33229071 HtrA2 is required for inflammatory responses in BMDMs via controlling TRAF2 stability in c 2021 Jan Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by the destruction of cartilage and bone. The present study aims to investigate the role of HtrA serine peptidase 2 (HtrA2) in the collagen-induced arthritis. The expressions of HtrA2 were determined in the database BioGPS and bone marrow-derived macrophages (BMDMs). The populations of myeloid and lymphoid cells were determined in wild type and HtrA2 knockout (HtrA2(MKO)) mice using flow cytometry. In addition, the expressions of pro-inflammatory cytokines (Il6, Tnf, and Il1β) were determined in the activated BMDMs from wild type (WT) and HtrA2(MKO) mice. STRING database was used to predict the interactive proteins of HtrA2 and Co-Immunoprecipitation was used to confirm these interactions. A collagen-induced arthritis model was established to investigate the effects of HtrA2 on the arthritis symptoms. It was found that HtrA2 reduction was associated with the activation of myeloid cells. Interestingly, HtrA2 deficiency did not affect the development of myeloid and lymphoid cells. Further studies demonstrated that HtrA2 deficiency suppressed the production of pro-inflammatory cytokines in BMDMs induced by lipopolysaccharide or CpG. Co-Immunoprecipitation results demonstrated that HtrA2 enhanced the stability of TNF receptor-associated factor 2 (TRAF2). HtrA2 participated in the activation of the inflammatory response in a collagen-induced arthritis model. In summary, HtrA2 modulates inflammatory responses in BMDMs by controlling TRAF2 stability in a collagen-induced arthritis mouse model.
33161771 Effectiveness and safety of non-tumor necrosis factor inhibitor therapy for anti-human T-c 2021 Sep OBJECTIVES: Our previous study showed that the effectiveness of tumor necrosis factor (TNF) inhibitors was attenuated in anti-human T-cell leukemia virus type 1 (HTLV-1) antibody-positive patients with rheumatoid arthritis (RA). We aimed to evaluate the effectiveness and safety of non-TNF inhibitors in anti-HTLV-1 antibody-positive patients with RA. METHODS: We reviewed patients with RA who received abatacept or tocilizumab as the first biologic agent. We used the data of patients treated with TNF inhibitors from our previous study to compare the effectiveness between the anti-HTLV-1 antibody-positive patients treated with TNF inhibitors and non-TNF inhibitors using the inverse probability of treatment weights (IPTW) method. RESULTS: A total of 359 patients were divided into anti-HTLV-1 antibody-negative and -positive patients of 332 and 27, respectively. No statistically significant difference was observed in the change in the clinical disease activity index between the anti-HTLV-1 antibody-positive and -negative patients. The results using the IPTW method showed a significant association between the non-TNF inhibitors treatment and a better response. None of the patients developed adult T-cell leukemia/lymphoma or HTLV-1-associated myelopathy/tropical spastic paraparesis during the 24 weeks. CONCLUSION: Our results indicate that non-TNF inhibitors treatment is safety, and the effectiveness is not attenuated also in anti-HTLV-1 antibody-positive patients.
32062477 The role of Chinese herbal medicine in the management of adverse drug reactions of lefluno 2020 Mar BACKGROUND: The high discontinuation rate in RA patients who use LEF might be attributed to their intolerance rather than irresponsibility. The concomitant administration of Leflunomide (LEF) with Chinese herbal medicine (CHM) provides a potential solution to preventing the adverse drug reactions (ADRs) induced by LEF during the treatment of rheumatoid arthritis (RA). PURPOSE: To investigate whether co-administration of LEF with CHM could bring in both increased therapeutic outcomes and reduced ADRs due to the framework of treatment at the level of entire body. STUDY DESIGN: The mechanism of LEF in RA treatment and the ADRs it induced was introduced based on recent papers. Reported clinical examples of CHM concurrent use with LEF was revealed to provide more evidence. The management of the ADRs caused by LEF was suggested by current researches on the concomitant therapy of CHM with LEF. RESULTS: The active ingredients, compounds and medicinal herbs all demonstrated properties in relieving toxicities and reducing ADRs when used with LEF and reported in several clinical cases. The wide application of concurrent use of CHM with LEF is however hindered by the complex pathogenesis of RA which requires further scientific grounds for diagnosis and treatment. CONCLUSION: This review introduced that the adoption of CHM is emerging as a novel strategy for the management of ADRs caused by LEF.
32237479 [Benefit and risk of Tripterygium Glycosides Tablets in treatment of rheumatoid arthritis 2020 Feb Rheumatoid arthritis(RA) has a high disability rate and is highly harmful. It has a long course of treatment and is prone to adverse reactions or events(ADR/ADE). Selection of drugs in particular shall give consideration to both benefits and risk. Tripterygium Glycosides Tablets(TGT) is one of the important drugs for the treatment of RA. It has a remarkable efficacy, but a strong toxicity, which is controversial in clinical use. The study was oriented to patients, and quantitatively evaluated the efficacy and risk of TGT in treatment of RA, providing an intuitive basis for clinical safety and effective application of TGT. A multi-criteria decision-making analysis(MCDA) model of TGT was built in the treatment of RA, and then benefit and risk indicators were weighted by SWING method. Totally 53 random clinical trials(RCT) in accordance with the evaluation criteria were included by Meta-analysis method. The RCT results were merged by Meta-analysis, indicating that compared with the conventional therapy of chemical immunosuppressant(CISD), TGT could improve the curative effect whether it was used alone or in combination with CISD, but it would increase the incidence of reproductive system damage. The combined administration with CISD would also increase the incidence of liver and kidney damages. Treatment outcomes varied according to the different conditions of the combined administration with CISD. Based on MCDA model and clinical results, the benefit value, risk value and benefit-risk value of different doses, courses and combined administration of TGT in the treatment with RA were compared. The results showed that when the benefit and risk of the drug were equally important to the patient, the benefit-risk value of the single administration of TGT was 59, while that of the combined administration of TGT and CISD was 39. Therefore, the benefit-risk value of the single administration of TGT was 100% better than the combined administration. When the combined administration of TGT and CISD is unavoidable, the benefit-risk value of low-dose TGT(0.10-0.99 mg·kg~(-1)·d~(-1)) was 48, while that of high-dose TGT was 36. Therefore, low-dose TGT combined with CISD was more easily accepted by patients. The 2 to 3-month treatment course had a benefit-risk value of 40, while the long treatment course had a benefit-risk value of 38. Based on existing evidences, the single administration of TGT may be better than the combined administration with CISD. If the patients need to combine with CISD to treat RA, low dosage and 2 to 3-month course may be relatively optimal.
33273808 Prediction of Targets of Curculigoside A in Osteoporosis and Rheumatoid Arthritis Using Ne 2020 PURPOSE: Network pharmacology is considered to be the next-generation drug development model that uses bioinformatics to predict and identify multiple drug targets and interactions in diseases. Here, network pharmacology was used to investigate the mechanism by which Curculigoside A (CA) acts in rheumatoid arthritis (RA) and osteoporosis. METHODS: First, TCMSP and SwissADME were applied to predict the druggability of CA. Then, potential targets were identified from overlapping data in SwissTarget and TargetNet, and targets were analyzed using Genemania and DAVID6.8 to obtain information about the GO and KEGG pathways. Ultimately, the drug-target-pathway network was identified after using Cytoscape 3.0 for visualization. Besides, qPCR was used to validate the predicted five major genes targets (EGFR, MAP2K1, MMP2, FGFR1, and MCL1). RESULTS: The results of TCMSP and SwissADME demonstrated that CA exhibits good druggability; 26 potential protein targets were classified by SwissTarget and TargetNet. The results of Genemania and DAVID6.8 indicated that CA probably caused anti-osteoporosis and anti-RA effects by regulating some biological pathways, especially nitrogen metabolism, estrogen signaling pathway, Rap1 signaling pathway, and PI3K/Akt signaling pathway. Besides, the result of Cytoscape 3.0 showed that the 26 targets participate in osteoporosis and RA-related pathways, metabolism, and other physiological processes. In vitro induced inflammation cell model experiments, the qPCR results showed that CA pretreatment significantly decreased the expression of EGFR, MAP2K1, MMP2, FGFR1, and MCL1 genes. CONCLUSION: These results suggested that network pharmacology may provide possible mechanism of how CA exerts therapeutic effects in osteoporosis and RA.
32460880 Home storage of biological medications administered to patients with rheumatic diseases. 2020 May 27 BACKGROUND: The inadequate storage of biopharmaceuticals may result in an ineffective therapeutic response since poor conservation can lead to the emergence of protein aggregates and cause immunogenicity in patients, which can increase the risk of adverse events by inducing the production of anti-drug antibodies. This can also lead to significant economic losses for public health, given the high cost of these medicines. The aim of this study was to verify whether the home storage of biopharmaceuticals dispensed by the Unified Public System was in accordance with the manufacturers' specified standards and whether external variables interfered with the correct home storage. METHODS: This was a prospective observational study. Patients with a confirmed diagnosis of rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis who were using a biologic exclusively dispensed by Unified Public System were included. Storage temperature was measured by digital thermometer inserted into the refrigerator of the participant's home. Fisher's exact test was performed to cross-reference the temperature data and the qualitative variables obtained using an epidemiologic questionnaire. Mean, minimum, maximum values and standard deviation were described in the quantitative data. Mann-Whitney non-parametric test was performed to the association between temperature excursion and the number of people in the house. RESULTS: A total of 81 participants were included and 67 (82.71%) did not maintain home storage correctly. The maximum temperature observed among all patients was 15.5 °C, the minimum was - 4.4 °C and the average was 5.6 °C (standard deviation 2.8); 10 (12.3%) had at least one negative temperature measured. The average time for participants who had an inadequate temperature record was 8 h and 31 min. Nine participants (90%) who stored the medication into the shelf/drawer below the freezer had a temperature excursion (p = 0.011). Most of the participants (88.5%) who stored their biopharmaceutical near the back side, close to the wall of the refrigerator had a negative temperature record (p < 0.001). CONCLUSION: Most of the study participants (82.71%) did not maintain adequate home storage conditions for their biopharmaceutical. Intrinsic factors of household refrigerators may be involved in temperature deviations.
32156708 Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new 2020 May OBJECTIVE: To analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. METHODS: Cross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies. RESULTS: We enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs 43%; Anti-Fib 73% vs 51%; Anti-CFFHP 38% vs 19%; Anti-CarP-IgA 51% vs 20%, p<0.05 for all comparisons). Serum titers of Anti-CarP were significantly higher in RA-ILD patients. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in the multivariate analysis (Anti-FCS (OR: 3.42; 95% CI: 1.13 to 10.40), Anti-Fib (OR: 2.85; 95% CI: 0.83 to 9.70), Anti-CFFHP (OR: 3.11; 95% CI: 1.06 to 9.14) and Anti-FCS-IgA (OR: 4.30; 95% CI: 1.41 to 13.04)). Similar findings were observed in the replication sample. CONCLUSIONS: Anti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation.
30740931 Three Quality Improvement Initiatives and Performance of Rheumatoid Arthritis Disease Acti 2020 Feb OBJECTIVE: Applying treat-to-target strategies in the care of patients with rheumatoid arthritis (RA) is critical for improving outcomes, yet electronic health records (EHRs) have few features to facilitate this goal. We undertook this study to evaluate the effect of 3 health information technology (health-IT) initiatives on the performance of RA disease activity measures and outcomes in an academic rheumatology clinic. METHODS: We implemented the 3 following initiatives designed to facilitate performance of the Clinical Disease Activity Index (CDAI): an EHR flowsheet to input scores, peer performance reports, and an EHR SmartForm including a CDAI calculator. We performed an interrupted time-series trial to assess effects on the proportion of RA visits with a documented CDAI. Mean CDAI scores before and after the last initiative were compared using t-tests. Additionally, we measured physician satisfaction with the initiatives. RESULTS: We included data from 995 patients with 8,040 encounters between 2012 and 2017. Over this period, electronic capture of CDAI scores increased from 0% to 64%. Performance remained stable after peer reporting and the SmartForm were introduced. We observed no meaningful changes in disease activity levels. However, physician satisfaction increased after SmartForm implementation. CONCLUSION: Modifications to the EHR, provider culture, and clinical workflows effectively improved capture of RA disease activity scores and physician satisfaction, but parallel gains in disease activity levels were missing. This study illustrates how a series of health-IT initiatives can evolve to enable sustained changes in practice. However, capture of RA outcomes alone may not be sufficient to improve levels of disease activity without a comprehensive treat-to-target program.
32530345 A review of upadacitinib in rheumatoid arthritis. 2020 Sep Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting the joints and is associated with significant levels of disability and reduced quality of life. Janus kinase (JAK) inhibitors are a relatively new class of small molecule oral treatments and offer an alternative for patients with RA who do not respond to conventional or biologic therapy. Upadacitinib is a JAK inhibitor engineered to be selective for JAK1, and has recently been approved for use in patients with moderate-to-severe RA. The purpose of this article is to provide a comprehensive review of upadacitinib, including preclinical development and characterization, phase I and II studies, and the phase III SELECT program. Ongoing trials of upadacitinib in additional indications, including spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, are also discussed.