Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 32506054 | Body mass index and treatment survival in patients with RA starting treatment with TNFα-i | 2020 Jun | OBJECTIVES: To study whether there is an association between body mass index (BMI) category and survival of various tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients in a real-life longitudinal international registry. METHODS: Data from 5230 patients with RA starting treatment with any TNFi were selected from the METEOR registry. Patients were divided into six BMI categories: 3.7% underweight, BMI<18.5 kg/m(2); 46% normal weight, BMI 18.5-25 kg/m(2); 32% pre-obesity, BMI 25-30 kg/m(2); 13% obesity class I, BMI 30-35 kg/m(2); 3.4% obesity class II, BMI 35-40 kg/m(2); and 1.6% obesity class III, BMI >40 kg/m(2). Time on treatment in the different BMI categories was compared for all TNFi combined and for the infliximab, adalimumab and etanercept separately, using Kaplan-Meier curves and Cox regression analyses. Cox regression analyses were adjusted for potential confounders, with follow-up censored at 5000 days. RESULTS: Patients in obesity class II (HR 1.28, 95% CI 1.06 to 1.54) and III (HR 1.67, 95% CI 1.29 to 2.18) and underweight patients (HR 1.30, 95% CI 1.07 to 1.58) showed statistically significantly shorter TNFi survival than normal weight patients. The effect in underweight patients was strongest for infliximab (HR 1.82, 95% CI 1.20 to 2.76), the effect in overweight patients was strongest for infliximab (category II (HR 1.49, 95% CI 0.98 to 2.26); category III (HR 1.46, 95% CI 0.79 to 2.71)) and etanercept (category II (HR 1.27 95% CI 0.98 to 1.65); category III (HR 1.79, 95% CI 1.25 to 2.55)). No significant effect modification from reported pain was found. CONCLUSION: Both underweight and overweight patients discontinued TNFi treatment earlier than normal weight patients, without evidence of reported pain as the main determinant. It remains uncertain what determines TNFi survival in individual patients. | |
| 32990050 | Frequency of real-world reported adverse drug reactions in rheumatoid arthritis patients. | 2020 Dec | OBJECTIVES: To describe the cumulative incidences of adverse drug reactions (ADRs) associated with disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients from real-world data (RWD), using the DREAM-RA registry, and to compare these with incidence frequencies mentioned in the Summary of Product Characteristics (SmPC). METHODS: All ADRs in patients with recorded use of adalimumab, etanercept, hydroxychloroquine, leflunomide, oral and subcutaneous methotrexate, and sulfasalazine from a single center participating in the DREAM-RA registry (n = 1,098 patients) that were directly sent to the Netherlands Pharmacovigilance Center Lareb were assessed. Cumulative incidences were calculated, described and compared to the most recently revised SmPCs. RESULTS: In total, 14 ADRs (≥5 case reports) associated with the use of one of the included DMARDs were reported with a higher estimated cumulative incidence compared to the SmPC. For hydroxychloroquine and sulfasalazine, 5 ADRs (≥5 case reports) mentioned with an 'unknown' incidence in the SmPC were reported as 'common' in this study. CONCLUSIONS: Although ADR data in the DREAM-RA registry were partly comparable with data in the SmPCs, RWD from this patient registry provided an added value to the currently available information on the incidences of ADRs associated with DMARDs in RA patients as described in SmPCs. | |
| 33380154 | Gastrointestinal tract involvement in mixed connective tissue disease (Sharp syndrome). | 2020 Summer | Mixed connective tissue diseases (MCTD) is a very rare autoimmune disease connecting clinical signs of systemic lupus, systemic sclerosis, polymyositis and rheumatoid arthritis. Clinical manifestations are very diverse. In some patients, the digestive tract is affected in varying degrees. The esophagus is affected most often, and patients are complaining of dysphagia. Morphologically, this disorder is similar to the injure in systemic scleroderma. In this case, we describe a unique case of a severe damage of digestive tract manifested by esophageal motility disorders, cachectization, ascites, and repeated ileus conditions. | |
| 32420963 | Frailty syndrome in rheumatoid arthritis and symptomatic osteoarthritis: an emerging conce | 2020 May 11 | Musculoskeletal conditions such as rheumatoid arthritis (RA) and symptomatic osteoarthritis (OA) were the leading cause of disability in developed countries and disproportionately affects older adults. Frailty is an emerging concept in rheumatology, which represents an important construct to aid in the identification of in- dividuals who are vulnerable to adverse events and less favourable outcomes. The prevalence of frailty among the community-dwelling population increases with age: it ranges from 7% to 10% in those aged over 65 years and to 20-40% among octogenarians. Among patients with RA, the prevalence of frailty is comparable to, or even greater, that of older geriatric cohorts and pre-frailty, a condition including a major health vulnerability between robust and frail, is much more prevalent in RA than in geriatric cohorts. Clinical OA is also associated with frailty and pre-frailty in older adults in European countries. The overall prevalence of clinical OA at any site was 30.4%; frailty was present in 10.2% and pre-frailty in 51.0 %. The diagnosis of frailty is usually clinical and based on specific criteria, which are sometimes inconsistent. Therefore, there is an increasing need to identify and vali- date robust biomarkers for this condition. In the literature, different criteria have been validated to identify frail older subjects, which mainly refer to two conceptual models: the Physical Frailty (PF) phenotype proposed by Fried and the cumulative deficit approach proposed by Rockwood. The purpose of this review was to quantita- tively synthesize published literature on the prevalence of frailty in RA and OA and summarize current evidence on the validity and practicality of the most commonly used screening tools for frailty. | |
| 32375861 | Serum calprotectin: a promising biomarker in rheumatoid arthritis and axial spondyloarthri | 2020 May 6 | BACKGROUND: Calprotectin (S100A8/S100A9 protein) is known as a damage-associated molecular pattern (DAMP) protein and reflects mainly neutrophil activation. Serum calprotectin levels might be a good alternative to acute-phase protein as a biomarker in inflammatory rheumatic diseases. The aim of this study is to investigate the association of serum calprotectin with disease activity and severity in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). METHODS: Serum calprotectin was measured in patients with RA, axSpA, and PsA from the prospective Swiss Clinical Quality Management (SCQM) registry. Asymptomatic first-degree relatives of RA patients were used as healthy controls (HC). Outcomes included swollen joint count (SJC), Disease Activity Score (DAS), Health Assessment questionnaire (HAQ), joint radiographs, and ultrasound power Doppler (USPD) score for RA; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS) and coxitis for axSpA; and SJC and Disease Activity Index for PSoriatic Arthritis (DAPSA) for PsA. Comparison of outcomes by calprotectin quartile levels was performed using Kruskal-Wallis tests for continuous outcomes or trend tests for categorical outcomes. RESULTS: A total of 1729 subjects [RA = 969, axSpA = 451, PsA = 237, and HC = 72] were included. Median levels of serum calprotectin were higher in each disease group compared to HC (p < 0.01). In RA patients, all clinical outcomes were statistically different between quartiles of serum calprotectin, indicating an association between calprotectin levels and higher disease activity (SJC, DAS, and USPD scores) and severity (joint radiographs and HAQ). In axSpA, an association between calprotectin levels and ASDAS score (p < 0.01) and prevalence of coxitis (p = 0.02) was observed. For PsA patients, SJC and DAPSA did not differ across calprotectin quartiles. CONCLUSIONS: This large study supports the association of serum calprotectin levels with disease activity in both RA and axSpA, but not in PsA. | |
| 31612762 | Changes in radiographic findings and plantar pressure distribution following forefoot reco | 2020 Nov | Objectives: To evaluate changes in radiographic findings and plantar pressure distribution after rheumatoid forefoot surgery.Methods: This study was performed on patients with rheumatoid arthritis (RA) who underwent Swanson implant arthroplasty for the 1st metatarsophalangeal (MTP) joint combined with shortening oblique osteotomy at the 2nd through 5th metatarsal necks (group Sw, 55 feet). The following two groups were used as controls: group NS, consisting of 75 feet in RA patients without scheduled forefoot surgery, and group HC, consisting of 24 feet in healthy female subjects. Plantar pressure distribution, and radiographic findings of hallux valgus angle, the angle between the metatarsal bones, talocalcaneal angle, calcaneal pitch angle and calcaneo-first metatarsal angle (CFMA) were measured pre- and one year postoperatively. Peak pressure was measured in nine sections.Results: Calcaneal pitch angle decreased and CFMA increased in group Sw. Peak pressure at the 1st interphalangeal joint (IP) and the 2nd and 3rd MTPs in group Sw decreased, while that at midfoot increased.Conclusion: While the clinical outcome in group Sw was favorable, postoperative longitudinal arch decreased. Postoperative peak pressure at the 2nd through 5th MTPs was comparable with that in group NS; however, it was significantly lower than that in group HC. | |
| 32209269 | The Management of Perioperative Immunosuppressant Medications for Rheumatoid Arthritis Dur | 2020 Aug | PURPOSE: Rheumatoid arthritis (RA) is a destructive inflammatory disease that commonly involves joints of the hand and wrist. Different recommendations exist for continuing or discontinuing immunosuppressant medications during the perioperative time period. The purpose of our study was to determine whether continuing or discontinuing medications (steroids, nonbiological, and/or biological disease-modifying antirheumatic drugs [DMARDs]) were associated with an increased or decreased risk of postoperative complications. METHODS: We performed a single-center, retrospective review of a cohort of RA patients who had elective hand surgery by a single surgeon. Patients were included if they had a documented diagnosis of seropositive RA by a rheumatologist and had elective hand surgery and/or a disease-related surgical procedure involving the upper extremity between January 2008 and August 2018. We stratified patients into different groups for comparison by classes of immunosuppressant medications for managing RA. These classes included corticosteroids, nonbiological DMARDs, biological DMARDs, and/or no medications. Immunosuppressant medications were then compared with no medications for the incidence of postoperative overall complications. RESULTS: Eighty-eight patients had elective hand and/or upper extremity surgeries for RA. Mean patient age at the time of surgery (± SD) was 55 ± 13 years (range, 24-74 years). Of these 88 patients, 8 (9%) overall complications occurred. Complications were wound healing failures (n = 5), tendon rupture (n = 1), hematoma (n = 1), and surgical-site infection (n = 1). Perioperative medications included steroids (n = 31), nonbiological DMARDs (n = 68), biological DMARDs (n = 5), and no medication (n = 27). There were no significant differences in overall complications between patients on immunosuppressant medications and those on no medications. Median (interquartile range) follow-up was 11.5 months (5-25.8) (range, 2-74 months). CONCLUSIONS: We found that patients who continued or discontinued medications within 1 dosing interval of their usual dose perioperatively had similar rates of complications following elective hand surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. | |
| 33101545 | Association of VPREB1 Gene Copy Number Variation and Rheumatoid Arthritis Susceptibility. | 2020 | OBJECTIVE: Copy number variation (CNV) is a structural variation in the human genome that has been associated with multiple clinical phenotypes. B cells are important components of rheumatoid arthritis- (RA-) mediated immune response; hence, CNV in the regulators of B cells (such as VPREB1) can influence RA susceptibility. In this study, we aimed to explore the association of CNV in the VPREB1 gene with RA susceptibility in the Pakistani population. METHODS: A total of 1,106 subjects (616 RA cases, 490 healthy controls) were selected from three rheumatology centers in Pakistan. VPREB1 CNV was determined using the TaqMan® CN assay (Hs02879734_cn, Applied Biosystems, Foster City, CA, USA), and CNV was estimated by using CopyCaller® (version 2.1; Applied Biosystems, USA) software. Odds ratio (OR) was calculated by logistic regression with sex and age as covariates in R. RESULTS: A significant association between >2 VPREB1 CNV and RA risk was observed with an OR of 3.92 (95% CI: 1.27 - 12.12; p = 0.01746) in the total sample. Whereas <2 CNV showed a significantly protective effect against RA risk in women with an OR of 0.48 (95% CI: 0.29-0.79; p = 0.00381). CONCLUSION: CNV > 2 of VPREB1 is a risk factor for RA in the total Pakistani population, while CNV < 2 is protective in women. | |
| 31967351 | IgA is the predominant isotype of anti-β2 glycoprotein I antibodies in rheumatoid arthrit | 2020 Jun | BACKGROUND: The aim of this study was to determine the frequency of anti-cardiolipin antibodies (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI) among Tunisian patients with rheumatoid arthritis (RA). METHODS: Ninety RA patients with positive anti-cyclic citrullinated antibodies (anti-CCP) and 90 healthy blood donors (HBD) were studied. aCL and aβ2GPI of isotype IgG, IgA and IgM were detected by ELISA. RESULT: The frequency of antiphopholipid antibodies (aPL) (aCL and/or aβ2GPI) was significantly higher in patients with RA than in HBD (35.5% vs 11.1%, P = .0001). The frequencies of aCL and aβ2GPI were significantly higher in patients than in healthy subjects (15.5% vs 5.5%, P = .04 and 32.2% vs 11.1%, P = .0005 respectively). aβ2GPI-IgA were significantly more frequent in patients than in the control group (26.7% vs 7.8%, P = .0007). In patients, aβ2GPI-IgA were significantly more frequent than aβ2GPI-IgG (26.7% vs. 6.7%, P = .0003) and aβ2GPI-IgM (26.7% vs 5.6%, P = .0001). In RA patients, the frequency of aβ2GPI was significantly higher than that of aCL (32.2% vs 15.5%, P = .008). aβ2GPI-IgA was significantly more frequent than aCL-IgA (26.7% vs 4.4%, P = .00005). The average titer of anti-CCP in aPL positive patients was significantly higher than in aPL negative patients (170.6 ± 50 RU/mL vs 147.7 ± 51 RU/mL, P = .04). Significant correlation was found between aβ2GPI-IgA and anti-CCP (r = .235, P = .026). CONCLUSIONS: aPL and particularly aβ2GPI-IgA are frequent in RA and are correlated with anti-CCP. | |
| 32165681 | Identification of highly potent and selective inhibitor, TIPTP, of the p22phox-Rubicon axi | 2020 Mar 12 | Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease linked to oxidative stress, which is associated with significant morbidity. The NADPH oxidase complex (NOX) produces reactive oxygen species (ROS) that are among the key markers for determining RA's pathophysiology. Therefore, understanding ROS-regulated molecular pathways and their interaction is necessary for developing novel therapeutic approaches for RA. Here, by combining mouse genetics and biochemistry with clinical tissue analysis, we reveal that in vivo Rubicon interacts with the p22phox subunit of NOX, which is necessary for increased ROS-mediated RA pathogenesis. Furthermore, we developed a series of new aryl propanamide derivatives consisting of tetrahydroindazole and thiadiazole as p22phox inhibitors and selected 2-(tetrahydroindazolyl)phenoxy-N-(thiadiazolyl)propanamide 2 (TIPTP, M.W. 437.44), which showed considerably improved potency, reaching an IC(50) value up to 100-fold lower than an inhibitor that we previously synthesized reported N8 peptide-mimetic small molecule (blocking p22phox-Rubicon interaction). Notably, TIPTP treatment showed significant therapeutic effects a mouse model for RA. Furthermore, TIPTP had anti-inflammatory effects ex vivo in monocytes from healthy individuals and synovial fluid cells from RA patients. These findings may have clinical applications for the development of TIPTP as a small molecule inhibitor of the p22phox-Rubicon axis for the treatment of ROS-driven diseases such as RA. | |
| 30051736 | Living With Rheumatoid Arthritis in Spain: A Qualitative Study of Patient Experience and t | 2020 Nov | The aim of this study was to explore the experience of Spanish people living with rheumatoid arthritis (RA) and the support these people received from health professionals, particularly nurses. Nineteen patients with >1 year diagnosis, disease activity moderate or severe (DAS28 > 3.2), and already treated with disease-modifying antirheumatic drugs (DMARDs) were interviewed. A thematic analysis was performed to interpret the discourses. The difficulties of symptom management; the need for home-adaptations, the difficulties of living with a deteriorating self-image; and the reluctant reliance on medication to control their disease were the main themes that emerged from the discourse analysis of this study. Nurses appeared to have a limited role in RA patients care, and focused primarily on giving information and training for biological therapies. RA patients in Spain would benefit from having contact with specialist nurses who could empower them to self-manage their disease, as happens in other countries. | |
| 32541082 | Circulating Small Noncoding RNA Biomarkers of Response to Triple Disease-modifying Antirhe | 2020 Dec 1 | OBJECTIVE: To identify small noncoding RNA (sncRNA) serum biomarkers that predict response to triple disease-modifying antirheumatic drug (DMARD) therapy in patients with early rheumatoid arthritis (RA). METHODS: Early RA patients entered into a treat-to-target management algorithm, with triple DMARD therapy (methotrexate, sulfasalazine, hydroxychloroquine). Patients were assessed following 6 months of therapy and classified as European League Against Rheumatism responders or nonresponders. RNA was isolated from 42 archived serum samples, collected prior to commencement of triple DMARD therapy. Small RNA sequencing was performed and the reads mapped to annotations in a database of human sncRNA. Differential expression analysis was performed, comparing responders (n = 24) and nonresponders (n = 18). RESULTS: Pretreatment levels of 4 sncRNA were significantly increased in nonresponders: chr1. tRNA131-GlyCCC (4.1-fold, adjusted P = 0.01), chr2.tRNA13-AlaCGC (2.2-fold, adjusted P = 0.02), U2-L166 (6.6-fold, adjusted P = 0.02), and piR-35982 (2.4-fold, adjusted P = 0.03). 5S-L612 was the only sncRNA significantly increased in responders (3.3-fold; adjusted P = 0.01). Reads for chr1. tRNA131-GlyCCC and chr2.tRNA13-AlaCGC mapped to the 5' end of each tRNA gene and were truncated at the anticodon loop, consistent with these sncRNA having roles as 5' translation interfering tRNA halves (tiRNA). CONCLUSION: Pretreatment levels of specific serum sncRNA might facilitate identification of patients more likely to respond to triple DMARD therapy. | |
| 32497675 | Anti-angiogenic effect of Shikonin in rheumatoid arthritis by downregulating PI3K/AKT and | 2020 Oct 5 | ETHNOPHARMACOLOGICAL RELEVANCE: Zicao is the dried root of Lithospermum erythrorhizon Sieb, et Zucc, Arnebia euchroma (Royle) Johnst, or Arnebia guttata Bunge and commonly used to treat viral infection, inflammation, arthritis and cancer in China.Shikonin (SKN) is a major active chemical component isolated from zicao. Previous research showed that SKN has anti-inflammatory, immunomodulatory and analgesic effects, and inhibits the development of arthritis and the condition of collagen arthritis (CIA) mice; nevertheless, its role in the angiogenesis of rheumatoid arthritis (RA) has not been elucidated. AIM OF THE STUDY: The purpose of this study was to investigate the antiangiogenic activity of SKN in CIA rats and various angiogenesis models. MATERIAL AND METHODS: The anti-arthritic effect of SKN on CIA rats was tested by arthritis score, arthritis incidence, radiological observation and histopathology evaluation of inflamed joints. Vessel density evaluated with CD31 immunohistochemistry/immunofluorescence in joint synovial membrane tissues of CIA rats, chick chorioallantoic membrane assay, rat aortic ring assay, and the migration, invasion, adhesion and tube formation of human umbilical vein endothelial (HUVEC) cells induced by tumor necrosis factor (TNF)-α were used to measured the antiangiogenenic activity of SKN. Moreover, the effect of SKN on the expression of angiogenic mediators, such as vascular endothelial growth factor (VEGF), VEGFR2, TNF-α, interleukin (IL)-1β, platelet derived growth factor (PDGF) and transforming growth factor (TGF)-β in sera and joint synovia of rats, and in TNF-α-induced MH7A/HUVEC cells were measured by immunohistochemistry, enzyme linked immunosorbent assay, Western blot and/or real-time polymerase chain reaction (PCR). Through the analysis of protein and mRNA levels of phosphoinositide 3-kinase (PI3K), Akt and PTEN, and the autophosphorylation of ERK1/2, JNK and p38 in joint synovia of rats and in TNF-α-induced HUVEC cells, the molecular mechanism of its inhibition was elucidated by using Western blot and/or real-time PCR. RESULTS: SKN significantly reduced the arthritis score and arthritis incidence, and inhibited inflammation, pannus formation, cartilage and bone destruction of inflamed joints in CIA rats. Partially, SKN remarkably decreased the immature blood vessels in synovial membrane tissues of inflamed joints from CIA rats. It also suppressed in vivo angiogenesis in chick embryo and VEGF(165)-induced microvessel sprout formation ex vivo. Meanwhile, SKN inhibited TNF-α-induced migration, invasion, adhesion and tube formation of HUVEC cells. Moreover, SKN significantly decreased the expression of angiogenic activators including VEGF, VEGFR2, TNF-α, IL-1β, PDGF and TGF-β in synovia of CIA rats and/or in MH7A/HUVEC cells. More interestingly, SKN downregulated PI3K and Akt, and simultaneously upregulated PTEN both at protein and mRNA levels in synovia tissues and/or in TNF-α-induced HUVEC cells. It also suppressed the phosphorylation and gene level of TNF-α-induced signaling molecules, as ERK1/2, JNK, and p38 in synovium and/or in TNF-α-induced HUVEC cells. CONCLUSION: These findings indicate for the first time that SKN has the anti-angiogenic effect in RA in vivo, ex vivo and in vitro by interrupting the PI3K/AKT and MAPKs signaling pathways. | |
| 32873774 | Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts. | 2020 Sep 1 | Cannabidiol (CBD) is a non-intoxicating phytocannabinoid from cannabis sativa that has demonstrated anti-inflammatory effects in several inflammatory conditions including arthritis. However, CBD binds to several receptors and enzymes and, therefore, its mode of action remains elusive. In this study, we show that CBD increases intracellular calcium levels, reduces cell viability and IL-6/IL-8/MMP-3 production of rheumatoid arthritis synovial fibroblasts (RASF). These effects were pronounced under inflammatory conditions by activating transient receptor potential ankyrin (TRPA1), and by opening of the mitochondrial permeability transition pore. Changes in intracellular calcium and cell viability were determined by using the fluorescent dyes Cal-520/PoPo3 together with cell titer blue and the luminescent dye RealTime-glo. Cell-based impedance measurements were conducted with the XCELLigence system and TRPA1 protein was detected by flow cytometry. Cytokine production was evaluated by ELISA. CBD reduced cell viability, proliferation, and IL-6/IL-8 production of RASF. Moreover, CBD increased intracellular calcium and uptake of the cationic viability dye PoPo3 in RASF, which was enhanced by pre-treatment with TNF. Concomitant incubation of CBD with the TRPA1 antagonist A967079 but not the TRPV1 antagonist capsazepine reduced the effects of CBD on calcium and PoPo3 uptake. In addition, an inhibitor of the mitochondrial permeability transition pore, cyclosporin A, also blocked the effects of CBD on cell viability and IL-8 production. PoPo3 uptake was inhibited by the voltage-dependent anion-selective channel inhibitor DIDS and Decynium-22, an inhibitor for all organic cation transporter isoforms. CBD increases intracellular calcium levels, reduces cell viability, and IL-6/IL-8/MMP-3 production of RASF by activating TRPA1 and mitochondrial targets. This effect was enhanced by pre-treatment with TNF suggesting that CBD preferentially targets activated, pro-inflammatory RASF. Thus, CBD possesses anti-arthritic activity and might ameliorate arthritis via targeting synovial fibroblasts under inflammatory conditions. | |
| 30704919 | Biological Treatment Patterns in Patients with Inflammatory Joint Diseases. Retrospective | 2020 Nov | OBJECTIVES: To describe the therapeutic management of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) in patients initiating treatment with biological agents. MATERIALS AND METHODS: Observational, retrospective, longitudinal study in 33 Spanish hospitals. Patients with RA, PsA and AS starting treatment with biological agents between September 2009 and August 2010 and a follow-up longer than 3 years were included. Clinical-demographic characteristics, drugs, biological therapy survival, and reasons for discontinuation or switching were analyzed. RESULTS: Four hundred and sixty-three patients were included (183 RA, 119 PsA and 161 AS), with a mean follow-up of 3.8 years. At the end of follow-up, a high proportion continued with the first biological prescribed (41.0% of RA, 59.7% of PsA and 51.6% of AS), 31.1%, 47.9% and 42.9% of RA, PsA and AS patients requiring dosage adjustments, respectively. There was temporary discontinuation in 8.2%, 8.4% and 15.5% of patients, and a switch of biologic agent was required in 37.7%, 26.1% and 24.2%. Definitive discontinuation occurred in 13.1%, 5.9% and 8.7% of RA, PsA and AS patients, respectively. Mean time to discontinuation or switching was 30.1 months for RA and 35.7 months for PsA and AS. CONCLUSIONS: Our results suggest that, in practice, half of patients with RA and two thirds with PsA or AS maintained the first biological, but with frequent dose adjustments. | |
| 31848232 | A follow-up study of occupational styrene exposure and risk of autoimmune rheumatic diseas | 2020 Feb | OBJECTIVES: Increased risk has been suggested for autoimmune rheumatic diseases following solvent exposure. The evidence for specific solvents is limited, and little is known about exposure-response relations. Styrene is an aromatic, organic solvent and the objective of this study was to analyse the association between occupational styrene exposure and autoimmune rheumatic diseases in men and women. METHODS: We followed 72 212 styrene-exposed workers of the Danish reinforced plastics industry from 1979 to 2012. We modelled full work history of styrene exposure from employment history, survey data and historical styrene exposure measurements. We identified cases in the national patient registry and investigated gender-specific exposure-response relations by cumulative styrene exposure for different exposure time windows adjusting for age, calendar year and educational level. RESULTS: During 1 515 126 person-years of follow-up, we identified 718 cases of an autoimmune rheumatic disease, of which 73% were rheumatoid arthritis. When adjusting for potential confounders and comparing the highest with the lowest styrene exposure tertile, we observed a statistically non-significantly increased risk of systemic sclerosis among women (incidence rate ratio (IRR)=2.50; 95% CI 0.50 to 12.50) and men (IRR=1.86; 95 % CI 0.50 to 7.00), based on 9 and 22 cases, respectively. Results were inconsistent for the other autoimmune rheumatic diseases examined. CONCLUSION: This study suggests an association between occupational styrene exposure and systemic sclerosis in men as well as in women but based on few cases. This is a new finding and has to be replicated before conclusions can be drawn. | |
| 32232711 | Long Non-coding RNA THRIL Mediates Cell Growth and Inflammatory Response of Fibroblast-Lik | 2020 Jun | The present study explored the possible functions and the underlying mechanism of tumor necrosis factor-α (TNF-α) and heterogeneous nuclear ribonucleoprotein L (hnRNPL)-related immunoregulatory lncRNA plasmacytoma variant translocation 1 (THRIL) in rheumatoid arthritis (RA). Serum samples were collected from patients with RA. Primary fibroblast-like synoviocytes (FLSs) were separated from synovial tissues and cultured for subsequent cell experiments by transfecting different vectors. The qRT-PCR analysis was employed for evaluating the levels of THRIL in the serum. Enzyme-linked immunosorbent assay (ELISA) analysis was employed to detect the levels of inflammatory cytokines. MTT assay and Annexin V-FITC/PI apoptosis assay were used to evaluate the cell viability and apoptosis, respectively. Besides, the levels of the apoptotic proteins and the pathway-related proteins were measured by western blotting. Pearson's correlation analysis was used to assess the correlation between THRIL and clinical parameters. THRIL was overexpressed in the blood of patients with RA as compared with healthy participants (p < 0.05). The THRIL levels in the RA blood sample were positively associated with TNF-α levels, DAS 28, and ESR (p < 0.001). TNF-α treatment significantly inhibited cell viability and enhanced cell apoptosis. Furthermore, it elevated the levels of IL-1β and MMP-3 (p < 0.05), whereas the suppression of THRIL reversed these effects in TNF-α-treated RA-FLSs (p < 0.05). Moreover, the reduced THRIL remarkably reduced the expression of p-PI3K and p-AKT (p < 0.05) in TNF-α-treated RA-FLSs. The present study revealed that THRIL could regulate cell growth and inflammatory response of FLSs by activating the PI3K/AKT signaling pathway, subsequently playing important roles in promoting the occurrence and development of RA. | |
| 32590315 | JAK-STAT inhibitors: Immersing therapeutic approach for management of rheumatoid arthritis | 2020 Sep | Rheumatoid arthritis is a world leading cause of musculoskeletal disease. With the introduction of biological agents as treatment alternatives the clinical possibilities have grown exponentially. Currently most common Disease-modifying anti-rheumatic drugs (DMARDs) treatment option involves intravenous or subcutaneous injection, and some patients struggle to respond to DMARDs or lose their primary reaction. An oral drug formulation with lowered costs of manufacturing and flexibility for healthcare workers to preferably perform treatment will result in decreased healthcare expenditures and increased medication compliance. The JAK-STAT inhibitors, a new class of small molecules drugs, fulfills these criteria and has recently shown efficacy in rheumatoid arthritis. Here we give a summary of how JAK-STAT inhibitors function and a detailed review of current clinical trials. Convincing clinical results suggest that therapeutic inhibition of the JAK proteins can effectively modulate a complex cytokine-driven inflammation. | |
| 32384128 | Improving risk-stratification of rheumatoid arthritis patients for interstitial lung disea | 2020 | OBJECTIVE: To determine the performance of 3 circulating markers for the diagnosis and the progression of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA). METHODS: Serum concentrations of 3 circulating markers, lung epithelial-derived surfactant protein D (SPD), chemokine CCL-18 and Krebs von den Lungen-6 glycoprotein (KL-6), were measured by ELISA in consecutive patients with established RA. These patients were recruited from 3 tertiary centers and they all had been investigated by chest high-resolution computed tomography (HRCT). For a subset of French patients, a follow-up HRCT was available (mean interval between HRCT: 3±1.5 years). RESULTS: Among the 147 included patients (age: 66 ± 12 years, 69% women, disease duration 11 ± 10 years), 40 (27%) had RA-ILD on chest HRCT. SPD, CCL18 and KL-6 concentrations were significantly higher in patients with RA-ILD. ROC curve analysis to assess the diagnostic abilities of the three markers for the diagnosis of RA-ILD showed a superiority of KL-6 (Area under the curve, AUC: 0.79 95% CI 0.72-0.86) compared to SPD (AUC: 0.66 95% CI 0.58-0.74) and CCL18 (AUC: 0.62, 95% CI 0.53-0.70). The sensitivity of KL-6 for the diagnosis of RA-ILD was 68% with a specificity of 83%. The combination of KL-6 with SPD and CCL18 improved its diagnostic ability, with increased sensitivity from 68% to 77%, specificity from 83% to 97%. Increased KL-6 levels were independently associated with the presence of RA-ILD after the adjustment on other RA-ILD risk factors. In the French subset with longitudinal data, baseline KL-6 serum levels were predictive of ILD progression and the degree of ILD progression on HRCT was proportional to baseline KL-6 concentrations. CONCLUSION: These results show that KL-6 is a relevant circulating marker for the diagnosis and might be an interesting marker for the progression of RA-ILD. | |
| 32167248 | [Small molecules treatment in rheumatoid arthritis]. | 2020 Mar 11 | If treatment target is not reached with a conventional disease-modifying antirheumatic drug (csDMARD) such as methotrexate in rheumatoid arthritis, it is recommended to use a biologic (bDMARD) or a Janus kinase (JAK) inhibitor, small synthetic molecules recently developed. Oral administration and short half-life can favour the choice of JAK inhibitors, as well as the opportunity to use it in monotherapy, even though co-treatment with csDMARD is recommended. As yet long-term studies are lacking, little is known about adverse effects although risk of herpes virus infections is clearly higher with JAK inhibitors than bDMARD treatments. |