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ID PMID Title PublicationDate abstract
31196641 Extra-articular Manifestations and Comorbidity in Rheumatoid Arthritis: Potential Impact o 2019 Jul Rheumatoid arthritis (RA) is associated with a wide variety of extra-articular manifestations and comorbidities, several of which can be organ- or even life-threatening. These extra-articular manifestations and comorbidities can also contribute to the physical disability and psychological morbidity of RA that lead to reduced quality of life, higher direct and indirect costs, and societal burden of the disease. Although the expansion of RA treatment options and adoption of treat-to-target approaches has reduced the incidence and severity of several nonarticular manifestations of RA, such as rheumatoid vasculitis and cardiovascular disease events, this does not seem to be shared by all RA comorbidities. Moreover, a number of highly prevalent and impactful RA-driven comorbidities, such as accelerated atherosclerosis, interstitial lung disease, and sarcopenia, can present clinically in the years before the manifestation of joint pain or observable synovitis. A larger proportion of patients with RA have atherosclerosis, myocardial dysfunction, interstitial lung disease, and sarcopenia that is subclinical in the preclinical and earliest clinical phases of RA, emphasizing the importance of targeting the pre-RA phase for the prevention of comorbidities that are often poorly responsive to treatment once they develop. Herein, we review the potential impact of pre-RA prevention on the incidence and burden of extra-articular manifestations and nonarticular comorbidities.
31692815 VEGF-C Gene Polymorphisms Increase Susceptibility to Rheumatoid Arthritis. 2019 Vascular endothelial growth factor C (VEGF-C) promotes angiogenesis, a prominent feature in rheumatoid synovitis, contributing to the perpetuation of the global burden of rheumatoid arthritis (RA). VEGF-C gene polymorphisms predict the risk of developing various human diseases, such as urothelial cell carcinoma, oral cancer and coronary artery disease. We sought to determine whether single nucleotide polymorphisms (SNPs) of the VEGF-C gene can predict the risk of RA. Our study recruited 210 patients with RA and 373 healthy controls between 2007 and 2015, and performed comparative genotyping for SNPs rs7664413, rs11947611, rs1485766, rs2046463 and rs3775194. In analyses adjusted for potential covariates, we found that compared with subjects with the A/A genotype of SNP rs11947611, those with the A/G genotype were 40% more likely to develop RA (adjusted odds ratio [AOR] 0.61; 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In addition, subjects lacking the A/A genotype (A/G, G/G) of SNP rs2046463 were more than twice as likely as those with the A/A genotype to require methotrexate (AOR 2.23, 95% CI 1.25 to 3.98; p = 0.01), while those who lacked the G/G genotype (G/C, C/C) in the SNP rs3775194 had a significantly lower risk of requiring prednisolone as compared with those with the G/G genotype (AOR 0.39, 95% CI 0.19 to 0.79; p = 0.01). Our findings suggest that VEGF-C gene polymorphisms might serve as a diagnostic marker and therapeutic target for RA therapy. Pharmacotherapies that modulate the activity of the VEGF-C gene may be promising for RA treatment.
30579253 Fangchinoline supplementation attenuates inflammatory markers in experimental rheumatoid a 2019 Mar The present study evaluated the anti-inflammatory activity of fangchinoline in rheumatoid arthritis-induced rats. Rats were grouped into sham (group I), rheumatoid arthritis (group II, control), fangchinoline (2 μM, group III), and fangchinoline (4 μM, group IV) groups. The serum levels of lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase, reduced glutathione (GSH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinases (MMPs), prostaglandin-E2 (PGE(2)), nitric oxide (NO), zinc, ceruloplasmin, uric acid, and copper were determined. Chondrocyte cell proliferation, reactive oxygen species (ROS), and cellular levels of TNF-α and IL-6 were assessed. Lipid peroxidation, GSH, SOD, catalase, and Gpx levels recovered to near normal levels by fangchinoline treatment. Fangchinoline treatment significantly reduced the TNF-α level by 17.8% and 40.8% in groups III and IV respectively, whereas IL-6 was significantly decreased by 23.2% and 45%, respectively. Fangchinoline treatment significantly decreased the MMP-3 level by 23.1% and 65.1% in groups III and IV respectively, whereas PGE(2) was significantly decreased by 31.8% and 63.8%, respectively. Fangchinoline treatment decreased NO, uric acid, ceruloplasmin, and copper levels, whereas the zinc content was increased. Chondrocyte proliferation was significantly reduced to 73.3%, 51.3%, and 42.4% at 2 μM, 4 μM, and 6 μM fangchinoline treatment respectively. Intracellular ROS, TNF-α, and IL-6 levels were significantly reduced in the chondrocytes. Protein expression of TNF-α was significantly decreased by 0.27-, 0.53-, and 0.67-fold at 2 μM, 4 μM, and 6 μM fangchinoline treatment respectively. In conclusion, fangchinoline is effective as an anti-inflammatory agent in rheumatoid arthritis-induced rats.
30822156 UBASH3A gene polymorphisms and expression profile in rheumatoid arthritis. 2019 Feb OBJECTIVES: Recent evidence has demonstrated that UBASH3A play a pivotal role in multiple autoimmune diseases. In this study, we explored the association between UBASH3A gene single-nucleotide polymorphisms (SNPs) and rheumatoid arthritis (RA) in a Chinese Han population. We also comparatively evaluated the UBASH3A expression profile in peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls. METHODS: Four UBASH3A polymorphisms (rs1893592, rs11203203, rs2277798, and rs3788013) were studied in 553 patients with RA and 587 controls in a Chinese population. Genotyping was performed using the Fluidigm 192.24 Dynamic Array Integrated Fluidic Circuit (IFC). For gene expression study, UBASH3A mRNA levels of 30 RA patients and 31 healthy individuals were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Data were analyzed by SPSS 19.0 software. RESULTS: A significant association between rs1893592 polymorphism and RA was found under all genetic models (all p<.05). We also discovered a significant association between rs3788013 polymorphism and RA in the allele and genotype distributions, as well as the recessive model (all p<.05). Moreover, we found the genotype distribution and allele frequency of rs1893592 were significantly associated with RF phenotype in the RA patients (χ(2) = 6.786, p=.034; χ(2) = 4.534, p=.033; respectively). We also found the genotype distribution and allele frequency of rs2277798 were significantly associated with anti-CCP phenotype in the RA patients (χ(2) = 7.873, p=.020; χ(2) = 4.473, p=.034; respectively). However, we did not detect any significant associations between rs11203203 and RA susceptibility and autoantibody profiles (all p>.05). The mRNA expression of UBASH3A was increased in PBMCs of patients with RA when compared to healthy controls (p=.001). CONCLUSIONS: Our observations suggested that the dysregulation of UBASH3A might be associated with the pathogenesis of RA, and UBASH3A gene polymorphisms (rs1893592 and rs3788013) might contribute to RA susceptibility in Chinese Han population.
30786801 Effect of biological agents on synovial tissues from patients with rheumatoid arthritis. 2020 Mar Objectives: To compare the inflammation of synovium before and after biological agents in the patients with rheumatoid arthritis (RA) and to investigate the association between synovial histopathology and disease activity.Methods: Synovial tissues were obtained during operations from 34 patients before and after treatment with biological agents. The synovial tissue was evaluated using hematoxylin and eosin staining. Synovial histopathology was evaluated by Rooney score.Results: The Rooney score was also significantly decreased after treatment with biological agents in all items (p < .001). After the treatment with biological agents, Moderate disease activity group had significantly higher scores of focal aggregates of lymphocytes (p = .02), diffuse infiltrates of lymphocytes (p = .019), and the Rooney total scores (p = .002) than remission and low disease activity groups.Conclusion: Our results demonstrated that biological agents significantly decreased the RA synovial inflammation and synovial histopathology in sublining layer reflected disease activity.
31086948 Toll-like receptor 7 regulates osteoclastogenesis in rheumatoid arthritis. 2019 Sep 1 This study aimed to determine the regulatory role of toll-like receptor 7 (TLR7) in receptor activator of nuclear factor kappa-B ligand (RANKL) production and osteoclast differentiation in rheumatoid arthritis (RA). In confocal microscopy, the co-expression of TLR7, CD55 and RANKL was determined in RA synovial fibroblasts. After RA synovial fibroblasts were treated with imiquimod, the RANKL gene expression and protein production were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis from peripheral blood CD14+ monocytes which were cultured with imiquimod was assessed by determining the numbers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. The signal pathways mediating the TLR7-induced RANKL expression and osteoclastogenesis were analysed after inhibition of intracellular signal molecules and their phosphorylation. Imiquimod stimulated the expression of TLR7 and RANKL and production of RANKL in RA synovial fibroblasts, increasing the phosphorylation of TRAF6, IRF7, mitogen-activated protein kinases (MAPK), c-Jun and NFATc1. When CD14+ monocytes were cultured with imiquimod or co-cultured with imiquimod-pre-treated RA synovial fibroblasts, they were differentiated into TRAP+ multinucleated osteoclasts in the absence of RANKL. TLR7 activation-induced osteoclastogenesis in RA through direct induction of osteoclast differentiation from its precursors and up-regulation of RANKL production in RA synovial fibroblasts. Thus, the blockage of TLR7 pathway could be a promising therapeutic strategy for preventing bone destruction in RA.
31002160 Abatacept alleviates rheumatoid arthritis development by inhibiting migration of fibroblas 2019 Apr OBJECTIVE: To investigate whether Abatacept could regulate the occurrence and progression of rheumatoid arthritis (RA) by mediating cell migration of fibroblast-like synoviocytes (FLS) via mitogen-activated protein kinase (MAPK) pathway. PATIENTS AND METHODS: Levels of MMP1, MMP3 and MMP13 in RA-FLS treated with Abatacept or MAPK pathway inhibitor were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The regulatory effect of Abatacept on MAPK pathway was detected by Western blot. Transwell assay was performed to access the role of Abatacept in regulating cell migration of RA-FLS. RESULTS: Abatacept treatment remarkably downregulated levels of MMP1, MMP3 and MMP13 in FLS, which were confirmed by qRT-PCR and ELISA. Migratory ability of FLS was inhibited by Abatacept treatment. Western blot results suggested that Abatacept treatment downregulated MAPK pathway-related genes in FLS. The effects of Abatacept on MMPs expressions and cell migration were partially reversed by SB203580 treatment, the MAPK pathway inhibitor. CONCLUSIONS: Abatacept inhibits FLS migration and MMPs expressions via inhibiting MAPK pathway, thereby inhibiting RA development.
30880555 The correlation between interleukin-34 and bone erosion under ultrasound in rheumatoid art 2020 Mar Background: Rheumatoid arthritis (RA) is a chronic inflammatory arthropathy characterized by excessive synovial hyperplasia and progressive joint destruction. Pro-inflammatory cytokines play major roles in the regulation of synovial inflammation. The contribution of interleukin-34 (IL-34) in RA pathogenesis has been strongly suggested in clinical studies.Aim: To investigate the correlation between plasma IL-34 and disease parameters in RA patients including disease activity score (DAS28), receptor activator of NF-[Formula: see text]B ligand (RANKL) concentration, synovitis and bone erosions under ultrasound.Methods: 60 RA patients and 20 healthy controls were from Huashan Hospital, patient's medical history, physical examination, laboratory examination and ultrasound data were collected and recorded, respectively. Blood samples of all participants were collected and the levels of IL-34 and RANKL were tested. The levels of IL-34 and RANKL in RA patients were compared with those of healthy controls. Furthermore, the correlation between IL-34, RANKL and disease parameters in RA patients was analyzed.Results: Both plasma levels of IL-34 and RANKL in RA patients were significantly higher than the healthy controls (p < .05). IL-34 was significantly related to disease activity scores (r = 0.43, p = .001); RANKL (r = 0.46, p = .0003) and bone erosions by ultrasound (r = 0.38, p = .002).Conclusions: The plasma IL-34 concentration in RA was significantly higher than the healthy controls and was significantly correlated with RANKL, as well as disease activity score and bone erosions by ultrasound. The IL-34 may be a new biological marker for disease activity and predictor for bone erosions in RA. Targeting IL-34 holds promise in the management of RA and, potentially, other osteoclasts driven diseases (erosive osteoarthritis and psoriatic arthritis for example).
31342647 Sarcopenia-associated factors in Japanese patients with rheumatoid arthritis: A cross-sect 2019 Sep AIM: To evaluate the prevalence rate and factors associated with sarcopenia in Japanese patients with rheumatoid arthritis. METHODS: We enrolled 240 consecutive patients with rheumatoid arthritis aged ≥65 years in this study. We examined clinical data: age, sex, body mass index, disease duration, rheumatoid factor positivity, anti-cyclic citrullinated peptide antibody positivity, biological or target synthetic disease-modifying antirheumatic drug use, methotrexate use, glucocorticoid use, C-reactive protein level, disease activity score in 28 joints-erythrocyte sedimentation rate, Health Assessment Questionnaire Disability Index, bone mineral density of the lumbar spine and total hip, grip strength, gait speed, and relative skeletal muscle mass index by bioelectrical impedance analysis. Sarcopenia was defined according to a consensus report by the Asian Working Group for Sarcopenia. RESULTS: The prevalence rate of sarcopenia was found to be 29.6%. Multivariate analysis identified the following factors to be associated with sarcopenia: age (P = 0.008; odds ratio 1.08), body mass index (P < 0.001; odds ratio 0.73), C-reactive protein (P = 0.017; odds ratio 1.76) and hip bone mineral density (P = 0.037; odds ratio 0.61). CONCLUSIONS: The sarcopenia-associated factors were age, body mass index, C-reactive protein and hip bone mineral density in Japanese patients with rheumatoid arthritis. Because the Health Assessment Questionnaire Disability Index, a standard measurement of function, cannot predict sarcopenia, the muscle mass needs to be measured while assessing changes in grip strength, body mass index, C-reactive protein and hip bone mineral density. Geriatr Gerontol Int 2019; 19: 907-912.
31196650 Considerations for Optimal Trial Design for Rheumatoid Arthritis Prevention Studies. 2019 Jul The field of rheumatology has made major contributions to medicine through the identification of cellular and molecular targets and with the development of therapies for the treatment of an impressive range of immune-mediated rheumatic diseases. In recent years new milestones have been achieved. These include the recognition of an "at risk" state, defined by distinct clusters of characteristics, including disease-specific autoantibodies in serum and symptom complexes that include inflammatory joint pain. Studies seeking to prevent high-risk individuals from progressing to a state of clinically apparent arthritis have been initiated. Here, exploiting the current evidence base, an experimental framework to inform trial design is described, taking into consideration study patient phenotypes and highlighting the impact of risk stratification and the options available for therapeutic intervention according to the different phases of the preclinical syndrome. Pragmatic primary end points and suggestions for a set of risk-focused trial outcome measures are proposed, including both clinical assessments and patient-reported outcome measures. Rheumatoid arthritis prevention studies provide an important experimental framework for generating deeper insights into risk stratification and for refining trial design in the future. To this end, a research agenda is suggested, together with some considerations for imaging and for biological sampling. This commentary concludes with some of the operational issues that arise from such studies and addresses some of the challenges associated with recruitment and retention of the at-risk trial participant.
30886858 Mental Health and Rheumatoid Arthritis: Toward Understanding the Emotional Status of Peopl 2019 INTRODUCTION: Rheumatoid arthritis (RA) is a long-term disorder significantly impairing the somatic, emotional, and psychological functioning of its sufferers. Previous research has shown that affected individuals are characterized by an increased level of anxiety and depression. Currently, there are two main treatment schemes for RA; the first uses anti-inflammatory drugs, and the second utilizes biologic agents. This begs the question whether sufferers differ in intensities of pain, anxiety, and depression depending on the type of treatment and what the determinants of these affective states in patients treated using different methods are. METHODS: The study comprised 85 patients affected by RA (including 57 receiving biologically inactive medication). Research participants filled out a set of questionnaires measuring levels of anxiety and depression, intensity of experienced pain, strategies of coping with pain, and ego resiliency. RESULTS: The collected data was analyzed through intergroup comparisons, calculating simple correlation coefficients, developing and solving regression equations. The results imply that the choice of treatment differentiates the intensity of pain experienced by patients. Those receiving biologic agents reported lower levels of pain compared to those taking anti-inflammatory medication. It has also been noted that there are distinct configurations of conditions conducive to anxiety and depression in both anti-inflammatory and biologic agent groups. DISCUSSION: The observed constellation of dependencies between variables indicates that the choice of treatment scheme differentiates pain levels. This confirms the assumption that pain intensity, coping strategies, and ego resiliency depend on the severity of anxiety and depression.
31324468 Disease progression in relation to pre-onset parity among women with rheumatoid arthritis. 2020 Feb OBJECTIVE: Rheumatoid arthritis (RA) often ameliorates during pregnancy and flares postpartum, but the relationship of pregnancy and childbirth to RA prognosis is unclear. We examined RA severity for association with parity prior to RA onset and asked whether time from birth (latency) and/or the mother's HLA genotype influenced results. METHODS: A cohort study was conducted of 222 women previously identified in a prospective study of newly diagnosed RA, who returned for follow-up evaluation a median of 8 years later. Stratified analyses using Mantel-Haenszel methods were conducted to evaluate 5 RA severity measures based on hand and wrist radiographs, physical exams, and Health Assessment Questionnaires for association with parity. RESULTS: Overall, we observed little evidence of altered risk of progression to severe RA in relation to pre-onset parity, adjusting for RA onset age and time to follow-up. Stratifying parous women who had only live births by latency (<15 years/15+ years) showed no difference in risk of severe RA compared to nulligravid women. Live birth deliveries were significantly protective for women with 0 but not for those with 1 or 2 copies of the RA risk-associated HLA-DRB1 shared epitope sequence for erosion score (RR 0.26 95% CI 0.09-0.89) and joint count (RR 0.28 95% CI 0.09-0.87). CONCLUSION: We observed little evidence of difference in severe RA by pre-onset parity overall. However, among women not predisposed to RA by possessing the risk-associated HLA genotype, parous women who had only live births had lower risk of progression to severe RA as measured by erosion score and joint count.
30369071 Qualitative Exploration of Triangulated, Shared Decision-Making in Rheumatoid Arthritis. 2019 Dec OBJECTIVE: Treat-to-target implementation in rheumatoid arthritis (RA) requires a shared decision-making (SDM) process. However, ability to pay is a major determinant of patient choice, but how this factor affects SDM is under-explored. METHODS: Visits at 4 RA clinics during which patients faced a decision to change their treatment were audiotaped between May 2016 and June 2017. Audiotapes were transcribed verbatim and analyzed using qualitative framework analysis. RESULTS: A total of 156 visits were analyzed. Most patients with RA, except those with effective insurance coverage, had deliberations disrupted or sidelined by third-party insurance providers having power to authorize the preferred disease-modifying antirheumatic drug choice. This triangulated SDM complicated efficiency in deliberations and timely treatment and was a barrier to shared engagement about health risks and symptom improvement typically found in patient-provider dyads. CONCLUSION: Rheumatology care providers should aim to incorporate treatment costs and ability to pay into their deliberations so that individualized out-of-pocket estimates can be considered during triangulated SDM at the point-of-care.
31309850 Repair of bone erosions in rheumatoid arthritis: a systematic literature review. 2019 Nov Objective: The aim of this study was to review the literature to identify studies reporting repair of erosions in rheumatoid arthritis (RA).Method: A systematic literature search for publications on the repair of erosions was performed in PubMed and Embase, limited to human adults and published in English. Titles, abstracts, and full reports of articles identified were screened by the first author and verified by the second author.Results: The search yielded 411 publications, of which 33 (20 articles and 13 case reports) suggested repair of erosions in RA. There was heterogeneity in study design and different definitions of repair were used. Twelve articles showed strong evidence of repair, in eight articles repair was probable, and in all 13 case reports repair was evident.Conclusion: Repair of erosions does occur in RA. The definition and frequency of repair vary and the possible clinical relevance is unclear, motivating further studies.
31587587 Disease activity and sleep quality in rheumatoid arthritis: a deeper look into the relatio 2020 Dec Objectives: This study looks deeper into the relationship between rheumatoid arthritis (RA) disease activity and distinct dimensions of sleep quality. Methods: The Pittsburgh Sleep Quality Index (PSQI) was administered to a cohort of 147 RA patients. Health-related quality of life (HRQoL) and fatigue were measured with the SF-12 and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) instruments, respectively, whereas RA activity was determined with the Disease Activity Score 28 joints (DAS28). Ethical approval for the study and informed consent from the participants were obtained. Results: Most patients were females (78.2%), and the mean age of the entire sample was 63.7 years. Most participants (77.6%) were poor sleepers (i.e. PSQI ≥ 5) who suffered from fatigue more than good sleepers (FACIT-F: 21.6 vs. 39.3, p < 0.001). Overall sleep quality correlated, in the expected directions, with disease activity (Spearman's rho = 0.87, p < 0.001), physical health (-0.66, p < 0.001), mental health (-0.71, p < 0.001), and fatigue (0.87, p < 0.001). PSQI and its component scores differed across patient subgroups with increasing RA activity, even after adjusting for confounding variables. Conclusion: RA disease activity distinctly affects sleep quality, and given the already demonstrated importance of good sleep, this 'deeper look' might contribute to the effort to improve HRQoL in RA patients.
30944206 LncRNA DILC participates in rheumatoid arthritis by inducing apoptosis of fibroblast-like 2019 May 31 IL-6 produced by human fibroblast-like synoviocytes (HFLS) promotes rheumatoid arthritis (RA), while lncRNA DILC regulates liver cancer stem cells by inhibiting IL-6. Therefore, lncRNA DILC may participate in RA. In the present study, we found that plasma lncRNA DILC was down-regulated, while IL-6 was up-regulated in RA patients than in healthy controls. Plasma levels of lncRNA DILC and IL-6 were significantly and inversely correlated only in RA patients. Overexpression of lncRNA DILC resulted in promoted apoptosis of HFLS isolated from RA patients, while lncRNA DILC siRNA silencing played an opposite role. In addition, overexpression of lncRNA DILC also resulted in inhibited IL-6 expression in HFLS isolated from RA patients. Therefore, lncRNA DILC may participate in RA by inducing apoptosis of HFLS and down-regulating IL-6.
31851711 Inferring disease severity in rheumatoid arthritis using predictive modeling in administra 2019 BACKGROUND: Confounding by disease severity is an issue in pharmacoepidemiology studies of rheumatoid arthritis (RA), due to channeling of sicker patients to certain therapies. To address the issue of limited clinical data for confounder adjustment, a patient-level prediction model to differentiate between patients prescribed and not prescribed advanced therapies was developed as a surrogate for disease severity, using all available data from a US claims database. METHODS: Data from adult RA patients were used to build regularized logistic regression models to predict current and future disease severity using a biologic or tofacitinib prescription claim as a surrogate for moderate-to-severe disease. Model discrimination was assessed using the area under the receiver (AUC) operating characteristic curve, tested and trained in Optum Clinformatics® Extended DataMart (Optum) and additionally validated in three external IBM MarketScan® databases. The model was further validated in the Optum database across a range of patient cohorts. RESULTS: In the Optum database (n = 68,608), the AUC for discriminating RA patients with a prescription claim for a biologic or tofacitinib versus those without in the 90 days following index diagnosis was 0.80. Model AUCs were 0.77 in IBM CCAE (n = 75,579) and IBM MDCD (n = 7,537) and 0.75 in IBM MDCR (n = 36,090). There was little change in the prediction model assessing discrimination 730 days following index diagnosis (prediction model AUC in Optum was 0.79). CONCLUSIONS: A prediction model demonstrated good discrimination across multiple claims databases to identify RA patients with a prescription claim for advanced therapies during different time-at-risk periods as proxy for current and future moderate-to-severe disease. This work provides a robust model-derived risk score that can be used as a potential covariate and proxy measure to adjust for confounding by severity in multivariable models in the RA population. An R package to develop the prediction model and risk score are available in an open source platform for researchers.
31408709 Expanding the citrullinome of synovial fibrinogen from rheumatoid arthritis patients. 2019 Sep 30 Citrullination is a post-translational protein modification, which is associated with inflammation in general and is thought to play an important pathogenic role in rheumatoid arthritis (RA). Here a mass spectrometry-based proteomics approach was applied to identify citrullination sites in synovial fluid fibrinogen from four RA patients. In general, high disease activity correlated with increased number of identified citrullination sites and higher relative citrulline occupancy. Altogether, 23 sites were identified, of which 9 have not been previously reported to be citrullinated in vivo. Citrullination at site α84, α123, α129, α547, α573, α591, β334 and γ134 was identified in more than one patient, and these positions were therefore regarded as hotspots. Following citrullination of fibrinogen in vitro using human recombinant peptidylarginine deiminase 2 (PAD2), a total of 46 citrullination sites were identified, including 6 hitherto unreported in vitro citrullination sites. Twenty-two out of the 23 citrullination sites identified in vivo were also detected in vitro, supporting the validity of the identifications. SIGNIFICANCE: This work provides information about previously uncharacterized citrullination sites in synovial fluid fibrinogen from rheumatoid arthritis patients. Detection of these novel citrullination sites may prove to have diagnostic or prognostic value in RA and enhance our understanding of the immune pathogenesis.
29696833 Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity and the Prob 2019 Jan OBJECTIVE: Optimal targeted treatment in rheumatoid arthritis requires early identification of failure to respond. This post hoc analysis explored the relationship between early disease activity changes and the achievement of low disease activity (LDA) and remission targets with tofacitinib. METHODS: Data were from 2 randomized, double-blind, phase III studies. In the ORAL Start trial, methotrexate (MTX)-naive patients received tofacitinib 5 or 10 mg twice daily, or MTX, for 24 months. In the placebo-controlled ORAL Standard trial, MTX inadequate responder patients received tofacitinib 5 or 10 mg twice daily or adalimumab 40 mg every 2 weeks, with MTX, for 12 months. Probabilities of achieving LDA (using a Clinical Disease Activity Index [CDAI] score ≤10 or the 4-component Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR] ≤3.2) at months 6 and 12 were calculated, given failure to achieve threshold improvement from baseline (change in CDAI ≥6 or DAS28-ESR ≥1.2) at month 1 or 3. RESULTS: In ORAL Start, 7.2% and 5.4% of patients receiving tofacitinib 5 and 10 mg twice daily, respectively, failed to show improvement in the CDAI ≥6 at month 3; of those who failed, 3.8% and 28.6%, respectively, achieved month 6 CDAI-defined LDA. In ORAL Standard, 18.8% and 17.5% of patients receiving tofacitinib 5 and 10 mg twice daily, respectively, failed to improve CDAI ≥6 at month 3; of those who failed, 0% and 2.9%, respectively, achieved month 6 CDAI-defined LDA. Findings were similar when considering improvements at month 1 or DAS28-ESR thresholds. CONCLUSION: In patients with an inadequate response to MTX, lack of response to tofacitinib after 1 or 3 months predicted a low probability of achieving LDA at month 6. Lack of an early response may be considered when deciding whether to continue treatment with tofacitinib.
29102587 Quality of Life in Ecuadorian Patients With Rheumatoid Arthritis: A Cross-sectional Study. 2019 Sep OBJECTIVES: To evaluate health-related quality of life (HRQoL) and associated clinical, demographic and socioeconomic factors in a cohort of Ecuadorian patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A cross-sectional descriptive study evaluating (HRQoL) with the Spanish version of the Quality of Life Rheumatoid Arthritis (QoL-RA) instrument in patients diagnosed with RA according to the criteria of the American College of Rheumatology and the European League Against Rheumatism. In addition, the following data were obtained: age, sex, marital status, socioeconomic stratum, comorbidities, disease duration, medication, rheumatoid factor positivity, disease activity using the simplified disease activity index and physical functionality measured with the modified Health Assessment Questionnaire (MHAQ). RESULTS: A total of 163 patients were assessed, the mean score of the QoL-RA scale was 6.84±1.5 points. The highest measurements were obtained in the domains of interaction (8.04±1.9) and support (8.01±2). The factors that were associated with the overall quality of life assessment were: functionality measured with MHAQ (r=-0.70; P<.001); disease duration in years (r=-0.178; P<.05); and disease activity (mean difference of 1.5; 95%CI: 1.09 to 1.91). CONCLUSION: The patients evaluated had a good to moderate HRQoL. The domains related to support and social life were those with the highest scores and the lowest scores were related to pain and nervous tension. Functionality, duration, and disease activity were statistically associated with HRQoL.