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ID PMID Title PublicationDate abstract
31848023 Factors associated with long-term persistence of rituximab in rheumatoid arthritis In clin 2020 Jul 10 BACKGROUND AND OBJECTIVE: Treatment of rheumatoid arthritis with rituximab (RTX) requires repeated cycles, but there is no well-established retreatment regimen in dose and frequency. The objective was to analyse the persistence of RTX treatment and factors that influence in terms of routine clinical practice. METHODS: Rituximab in Rheumatoid Arthritis (RITAR Study) is an observational, retrospective study that analyses the persistence of RTX in a cohort from 2003 to 2015. Persistence was calculated by the Kaplan-Meier analysis; curves were compared with the Log-Rank test. Cox regression was used to quantify the risk of discontinuation and multivariate analyses were conducted to determine the factors associated with the persistence of the treatment. RESULTS: 454 cycles of RTX in 114 patients were included. Median survival was 10.0 years and incidence rate of discontinuation was 7.7 per 100 patients/year. Factors associated with persistence were autoantibody positivity and use of RTX in combination with csDMARDs. Sex, age, number of comorbidities, rheumatoid arthritis evolution, number of complications, basal DAS28, basal HAQ, number of lines of treatment, fixed or on demand retreatment and year of RTX starting were not associated. Multivariable models confirmed the relationship between autoantibody positivity, monotherapy and persistence of RTX. CONCLUSIONS: The persistence of RTX in clinical practice is higher in seropositive patients and in those who are treated with RTX associated with a csDMARD. Dose per cycle and retreatment frequency do not have a decisive role in rituximab persistence.
31762409 RTD-1 therapeutically normalizes synovial gene signatures in rat autoimmune arthritis and 2019 Dec 1 Rhesus theta defensin-1 (RTD-1), a macrocyclic immunomodulatory host defense peptide from Old World monkeys, is therapeutic in pristane-induced arthritis (PIA) in rats, a model of rheumatoid arthritis (RA). RNA-sequence (RNA-Seq) analysis was used to interrogate the changes in gene expression in PIA rats, which identified 617 differentially expressed genes (DEGs) in PIA synovial tissue of diseased rats. Upstream regulator analysis showed upregulation of gene expression pathways regulated by TNF, IL1B, IL6, proinflammatory cytokines, and matrix metalloproteases (MMPs) involved in RA. In contrast, ligand-dependent nuclear receptors like the liver X-receptors NR1H2 and NR1H3 and peroxisome proliferator-activated receptor gamma (PPARG) were downregulated in arthritic synovia. Daily RTD-1 treatment of PIA rats for 1-5 days following disease presentation modulated 340 of the 617 disease genes, and synovial gene expression in PIA rats treated 5 days with RTD-1 closely resembled the gene signature of naive synovium. Systemic RTD-1 inhibited proinflammatory upstream regulators such as TNF, IL1, and IL6 and activated antiarthritic ligand-dependent nuclear receptor pathways, including PPARG, NR1H2, and NR1H3, that were suppressed in untreated PIA rats. RTD-1 also inhibited proinflammatory responses in IL-1β-stimulated human RA fibroblast-like synoviocytes (FLS) in vitro and diminished expression of human orthologs of disease genes that are induced in rat PIA synovium. Thus, the antiarthritic mechanisms of systemic RTD-1 include homeostatic regulation of arthritogenic gene networks in a manner that correlates temporally with clinical resolution of rat PIA.
31565240 Ultrasound is not associated with the presence of systemic autoimmunity or symptoms in ind 2019 OBJECTIVE: To identify whether musculoskeletal ultrasound (MSUS) abnormalities are associated with specific phases of rheumatoid arthritis (RA) development in individuals at risk of RA. METHODS: This is a prospective cohort study of individuals at risk of developing RA, namely first-degree relatives of patients with RA (RA-FDRs) without evidence of established rheumatic disease at inclusion. The inflammatory activity on MSUS was assessed according to a validated score (SONAR). Active MSUS was defined as a total B-mode score greater than 8, including at least one joint with significant synovitis (grade 2 or 3) or significant synovial hyperaemia (Doppler score greater than 1). We used logistic regression to analyse associations between MSUS findings and recognised preclinical phases of RA development, adjusting for other demographic and biological characteristics. RESULTS: A total of 273 RA-FDRs were analysed, of whom 23 (8%) were anticitrullinated protein autoantibodies-positive, 58 (21%) had unclassified arthritis and 96 (35%) had an active MSUS, which was only associated with unclassified arthritis (OR: 1.8, 95% CI 1.0 to 3.3). CONCLUSION: In individuals at risk of RA, active MSUS was associated with the presence of unclassified arthritis, but not with any of the earlier described phases of RA development. These findings do not support an indiscriminate use of ultrasound in a screening strategy for preclinical RA.
31269834 Possible role of β-galactosidase in rheumatoid arthritis. 2020 Jul Objective: To investigate the potential role of β-galactosidase in altering immunoglobulin G (IgG) galactosylation in serum of rheumatoid arthritis (RA).Methods: The expression level and activity of β-galactosidase in serum and CD 19(+) B cells were measured by enzyme-linked immune sorbent assay (ELISA). The effect of β-galactosidase on the N-glycan changes in serum from mice intravenously treated with β-galactosidase was observed by linear ion-trap quadrupole-electrospray ionization mass spectrometry (LTQ-ESI-MS). We established a collagen-induced arthritis (CIA) rat model to explore the biological function of β-galactosidase in RA.Results: The expression level of β-galactosidase in serum of 32 patients was elevated when compared with those of 30 healthy controls. The activity and expression level of β-galactosidase in CD19(+) B cells from RA patients was higher than those from healthy controls. The ratio of m/z 1142/937 was reduced in mice treated with β-galactosidase when compared with normal mice. We found that β-galactosidase was implicated in the development of inflammation by affecting body weight and elevating the expression level of interleukin-6, tumor necrosis factor-α, and rheumatoid factor in the serum.Conclusions: Our results suggested the high level of β-galactosidase in B cells and serum of RA patients and revealed that altered β-galactosidase may be implicated in the progression of inflammation.
31245894 Correlation of microRNA expression profile with clinical response to tumor necrosis factor 2019 Sep BACKGROUND: This study aimed to explore the correlation of circulating microRNA (miRNA) expression profile with clinical response to tumor necrosis factor (TNF) inhibitor in treating rheumatoid arthritis (RA) patients. METHODS: Baseline PBMC samples from eight responders and eight non-responders after 24-week TNF inhibitor (etanercept) treatment were subjected to miRNA microarray. Then, top 10 dysregulated miRNAs were selected and further validated by quantitative polymerase chain reaction (qPCR) in baseline PBMC samples from 92 RA patients treated with 24-week TNF inhibitor (etanercept). Responders and non-responders were divided referring to the decline in disease activity score in 28 joints. RESULTS: In microarray assay, total 59 upregulated and 78 downregulated miRNAs were identified in responders compared to non-responders, which were mainly enriched in regulating immune- and inflammation-related biological processes and pathways. The top 10 dysregulated miRNAs were as follows: miR-192-5p, miR-146a-5p, miR-19b-3p, miR-320c, miR-335-5p, miR-149-3p, miR-766-3p, let-7a-5p, miR-24-3p, and miR-1226-5p. In qPCR validation, miR-146a-5p was increased, while let-7a-5p was decreased in responders compared with non-responders. Multivariate logistic analysis illuminated that miR-146a-5p and CRP independently correlated with higher clinical response, while let-7a-5p and biologics history independently associated with lower clinical response. Subsequently, receiver operating characteristic curve showed that combination of these four independent factors presented with a great predictive value for clinical response with area under curve: 0.863, 95% CI 0.781-0.945. CONCLUSION: miRNA expression profile is closely implicated in the treatment efficacy of TNF inhibitor, and combined measurement of miR-146a-5p, let-7a-5p, CRP, and biologics history disclosed a great predictive value for clinical response to TNF inhibitor in RA patients.
31292709 A phase III study of BCD-055 compared with innovator infliximab in patients with active rh 2019 Sep BCD-055 is a biosimilar of innovator infliximab (IFX). Here we present the 54-week results from phase 3 clinical study in patients with rheumatoid arthritis (RA). The aim of this study was to demonstrate the equivalent efficacy and safety of BCD-055 and IFX in patients with active rheumatoid arthritis. 426 adults with active RA were enrolled. Patients were randomized into 2 study arms in 2:1 ratio to receive BCD-055 or IFX innovator in dose of 3 mg/kg at week 0, 2, 6 and then every 8 weeks up to week 54. Primary efficacy endpoint was the rate of American College of Rheumatology (ACR) 20 response at week 14. The equivalence margin was set as 15%. Immunogenicity and safety were also assessed. Rate of ACR20 at week 14 in PP (Per-Protocol) population was 71.2% in BCD-055 group and 67.9% in IFX group. Difference in ACR20 rates between groups was 3.2% with 95% CI [- 7.0%; 13.5%] (р = 0.587). Throughout 54-week study period, both groups were characterized by similar rates of ACR20/50/70 response at all timepoints without significant differences (p > 0.05). The rates of adverse events (AE) were similar in groups (74.64% in BCD-055 arm vs 66.67% in IFX arm, p = 0.111). Antibodies to infliximab were detected in 28.46% patients for BCD-055 arm and 26.56% for IFX arm (p = 0.786). BCD-055 and IFX were comparable in efficacy (including radiographic progression), safety and immunogenicity throughout the 54-week study.Trial registration ClinicalTrials.gov ID, number NCT02762838.
31491682 Influence of blue mussel (Mytilus edulis) intake on fatty acid composition in erythrocytes 2019 Nov Intake of blue mussels decreased disease activity in women with rheumatoid arthritis (RA) in the randomized cross-over MIRA (Mussels, inflammation and RA) trial. This study investigates potential causes of the decreased disease activity by analysing fatty acid composition in erythrocytes and plasma phospholipids and serum metabolites in samples from the participants of the MIRA trial. Twenty-three women completed the randomized 2 × 11-week cross-over dietary intervention, exchanging one cooked meal per day, 5 days a week, with a meal including 75 g blue mussels or 75 g meat. Fatty acid composition in erythrocytes and plasma and (1)H Nuclear Magnetic Resonance ((1)H NMR) metabolomics data were analysed with multivariate data analysis. Orthogonal Projections to Latent Structures with Discriminant Analysis (OPLS-DA) and OPLS with effect projections (OPLS-EP) were performed to compare the two diets. The fatty acid profile in erythrocytes was different after intake of blue mussels compared to the control diet, and all samples were correctly classified to either the blue mussel diet or control diet. Changes following blue mussel intake included significant increases in omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at the group level but not for all individuals. The fatty acid profile in plasma phospholipids and (1)H NMR serum metabolites did not differ significantly between the diets. To conclude, modelling fatty acids in erythrocytes may be a better biomarker for seafood intake than only EPA and DHA content. The change in fatty acid pattern in erythrocytes could be related to reduction in disease activity, although it cannot be excluded that other factors than omega-3 fatty acids potentiate the effect.
31515933 Dose down-titration of biological disease-modifying antirheumatic drugs in daily clinical 2019 Nov AIM: To determine characteristics of rheumatoid arthritis (RA) patients in Japan who received the same biological disease-modifying antirheumatic drugs (bDMARDs) for at least 6 months and to identify factors associated with successful down-titration of bDMARDs dependent on shared decision-making. METHODS: We included consecutive RA patients who received the same bDMARD with low disease activity or remission for at least 6 months in our two university hospitals. Patients treated with the bDMARD standard dose were defined as SD, while those treated with bDMARD down-titration were defined as DT. We retrospectively reviewed clinical charts and compared data between the two groups. RESULTS: Of 288 patients with RA, 204 (70.8%) and 84 (29.2%) continued standard dose treatment and underwent down-titration treatment, respectively. Sixty-six of 84 (78.6%) down-titration-treated patients continued to show low disease activity or remission, whereas 18 (21.4%) relapsed 18.9 ± 24.4 months after bDMARD down-titration was started. Univariate predictor analysis showed that the probable factors of down-titration were no history of bDMARD treatment (P = .001) and low initial Disease Activity Assessment of 28 joint score (P = .048). Other clinical characteristics had no significant relationship with successful down-titration. CONCLUSIONS: Thus, bDMARD-naïve patients and those with low initial disease activity are more likely to agree to attempt down-titration. However, the timing and method of down-titration should be made in shared decision-making between patients and rheumatologists.
31805992 Circulating calprotectin (S100A8/A9) is higher in rheumatoid arthritis patients that relap 2019 Dec 5 OBJECTIVE: To investigate whether calprotectin (S100A8/A9 or MRP8/14), an inflammatory complex released by monocytes, could indicate residual subclinical inflammation in rheumatoid arthritis (RA) patients who are in stable remission on disease-modifying anti-rheumatic drugs (DMARDs) and serve as a marker for disease flare after DMARD tapering. METHODS: We used data from two trials. Patients from the IMPROVED study had early (< 2 years) RA, and when they achieved disease activity score remission (DAS44 < 1.6), they stopped methotrexate to attempt drug-free remission. Patients from the RETRO study had established RA in stable remission (DAS28 < 2.6) and either tapered by 50% or stopped (biological or conventional) DMARDs. Circulating calprotectin at the tapering time point was determined by ELISA, and its predictive value for flare (loss of remission) within 12 months of DMARD tapering/stopping was determined. RESULTS: In both IMPROVED (n = 104) and RETRO (n = 57), patients that flared within 12 months had higher calprotectin at the moment of DMARD tapering/stopping. Twofold higher calprotectin at the moment of DMARD tapering/stopping was associated with an increased risk (odds ratio) of flare of 1.07 (95% CI 0.98-1.18, p = 0.14) in the IMPROVED and 3.62 (95% CI 1.76-7.46, p < 0.001) in the RETRO. Correcting for clinical predictors of flare (DAS at study inclusion, anti-CCP2 positivity, gender) did not change these estimates. The area under the receiver operating curve of calprotectin levels for predicting flare within 12 months was 0.63 (95% CIs 0.51-0.76) in the IMPROVED study and 0.80 (95% CIs 0.69 to 0.92) in the RETRO study. CONCLUSION: Circulating calprotectin levels in RA patients in remission on DMARDs are higher in patients that will flare upon DMARD tapering/stopping. Since the differences between the cohorts precluded definitive conclusions, more research is needed to determine whether calprotectin has prognostic value in predicting flare after attempting drug tapering in RA. TRIAL REGISTRATION: IMPROVED, ISRCTN11916566. RETRO, 2009-015740-42.
30761837 Abnormal retinal microvasculature found in active rheumatoid arthritis:a different perspec 2019 Feb 11 BACKGROUND/AIM: We aimed to assess the association between retinal vascular caliber (RVC) scores and disease activity in rheumatoid arthritis (RA) patients. MATERIALS AND METHODS: Forty-seven RA patients, 32 systemic lupus erythematosus (SLE) patients, and 45 healthy people were enrolled. RA and SLE patients were subdivided into groups according to C-reactive protein (CRP) levels. RA patients were also grouped according to Disease Activity Score-28 (DAS-28). Fundus photography was performed for all patients. RVC was summarized as the central retinal artery and vein equivalents (CRAE and CRVE). RESULTS: Mean CRVE for RA patients was 213.3 ± 17.8 μm compared with 209.2 ± 14.1 μm for SLE and 217.5 ± 26.2 μm for the control group (P = 0.17). RVC scores did not differ between the CRP-high and CRP-low groups. As the RA disease activity increased, the widening of CRVE became more prominent and statistically significant. When the DAS-28 > 5.1 (CRVE, 220.4 (211.8–246.5) μm) group and DAS-28 ≤ 3.2 (CRVE, 214.4 (172.4–242.3) μm) group were compared, statistical significance was more pronounced (P = 0.03) than when comparing the DAS-28 > 3.2 and DAS-28 ≤ 3.2 groups (P = 0.05). CONCLUSIONS: CRVE, which reflects systemic inflammation and possibly increased cardiovascular risk, was significantly increased in active RA patients. The association between retinal venular widening and disease activity, regardless of CRP, may be a sign that RA-related inflammation may have systemic vascular effects even with normal levels of CRP.
31266625 Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Other Populations and Newer 2019 Aug Because of the relatively high prevalence of both hepatitis B infection and various forms of autoimmune inflammatory diseases treated with aggressive immunotherapy, reactivation of hepatitis B occurs in a substantial number of patients. The risk of reactivation depends on the degree and duration of immunosuppression. A large number of drug treatments have resulted in reactivation of hepatitis B virus infection and, based on the mechanisms and extent of immunosuppression, recommendations for some of the newer classes of immunosuppressive drugs are provided.
31621054 The Selective Oral Immunomodulator Vidofludimus in Patients with Active Rheumatoid Arthrit 2019 Dec INTRODUCTION: The dihydroorotate dehydrogenase (DHODH) inhibitors leflunomide and teriflunomide are immunomodulatory agents approved to treat rheumatoid arthritis (RA) and multiple sclerosis, respectively, and are actively being investigated as therapeutic agents for other immune-related diseases; however, both structurally related compounds have a number of potentially serious adverse effects. Vidofludimus, a new selective second-generation DHODH inhibitor, is chemically distinct from leflunomide/teriflunomide and appears to exhibit a distinct safety profile. OBJECTIVE: The aim of the COMPONENT study was to assess the efficacy, safety, and pharmacokinetics of vidofludimus in the treatment of patients with active RA on a background therapy of methotrexate. This report focuses solely on the safety results of the COMPONENT trial. METHODS: Patients received once-daily oral vidofludimus (N = 122) or placebo (N = 119) along with their standard of care methotrexate treatment for 13 weeks. Efficacy endpoints were assessed. Safety parameters were monitored throughout treatment and at follow-up. Plasma concentrations of vidofludimus were measured. RESULTS: The primary efficacy endpoint, American College of Rheumatology 20 (ACR(20)) responder rate at 13 weeks, demonstrated numerical superiority in the treatment group compared with placebo; however, it did not reach statistical significance. Nonetheless, the COMPONENT study yielded important safety and pharmacokinetic data that could provide important information regarding the use of vidofludimus in other clinical trials, not only for RA but also for other autoimmune diseases. A safety profile for vidofludimus similar to placebo was obtained in this RA patient population. This includes similar rates of the adverse events of diarrhea, alopecia, neutropenia, and elevated liver enzymes, all of which are known drug-related adverse events reported for leflunomide and teriflunomide. A potential pharmacokinetic interaction between vidofludimus and methotrexate was observed. CONCLUSIONS: Vidofludimus demonstrated a positive safety profile, making it a promising candidate for the treatment of a variety of immune-related diseases. TRIAL REGISTRATIONS: ClinicalTrials.gov identifier: NCT01010581.
30808623 Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of fo 2019 May OBJECTIVES: Mortality in patients with rheumatoid arthritis (RA) is higher than in the general population. We investigated mortality in the COBRA-trial cohort after 23 years follow-up, compared with a reference sample of the Dutch population. METHODS: The COBRA-trial randomised patients with early RA to sulfasalazine monotherapy (SSZ, n=79) or a combination of SSZ, low-dose methotrexate and initially high, step-down prednisolone (COBRA, n=76). We compared the mortality in the COBRA-trial up to 2017 to a reference sample of the general population in the Netherlands (standardised mortality ratio, SMR), and its relation to early prognostic factors through stepwise Cox regression. RESULTS: Duration of follow-up in patients alive was mean 23 (range 22-24) years. In total, 44 patients died (28%, SMR=0.80 [95% CI 0.59 to 1.06]); 20 of 75 COBRA patients (27%, SMR 0.75 [0.47 to 1.14]) and 24 of 79 SSZ patients (30%, SMR 0.85 [0.56 to 1.25]); p=0.61). In the reference sample of the general population, 55 people (36%) died. 5 factors were significantly associated with increased mortality hazard: damage progression at 28 weeks; high Health Assessment Questionnaire (HAQ) score and absence of HLA-DR 2 or 3; disease duration from start of complaints was also significant, but showed an uninterpretable pattern. CONCLUSIONS: This prospective trial cohort study of early RA is one of the first to show similar mortality compared with the general population after 23 years of follow-up. It confirms that early, intensive treatment of RA has long-term benefits and suggests that treating to target is especially important for patients with poor prognosis.
29532704 Low body mass index and lymphocytopenia associate with Mycobacterium avium complex pulmona 2019 Jan OBJECTIVES: Patients with rheumatoid arthritis (RA) are at an increased risk of Mycobacterium avium complex pulmonary disease (MAC-PD). We aimed to identify factors associated with MAC-PD in RA patients, and investigate their clinical significance for diagnosis of this disease. METHODS: We examined 396 patients with RA for the presence of MAC-PD, using the criteria of the American Thoracic Society and conducted three years of follow-up on these patients. Multivariate logistic analyses were employed for selecting factors associated with MAC-PD. We developed a point system based on these factors which we call MAC-PD score to improve diagnosis of MAC-PD. RESULTS: During this study, 14 out of 396 patients were newly diagnosed with MAC-PD. Multivariate analyses revealed body mass index (BMI) <18.0 kg/m(2) and lymphocyte count <1500/μl were associated with MAC-PD in RA patients. Points were assigned to them and totalled to provide the MAC-PD score. Among 20 patients with high-resolution computer tomography images consistent with MAC-PD, the scores were significantly higher in 14 patients with MAC-PD than those in six patients without MAC-PD. CONCLUSION: Using these data, in the forms of the MAC-PD score, could help to identify patients who should be considered for bronchoscopy more selectively.
31443349 The Adipokine Network in Rheumatic Joint Diseases. 2019 Aug 22 Rheumatic diseases encompass a diverse group of chronic disorders that commonly affect musculoskeletal structures. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common, leading to considerable functional limitations and irreversible disability when patients are unsuccessfully treated. Although the specific causes of many rheumatic conditions remain unknown, it is generally accepted that immune mechanisms and/or uncontrolled inflammatory responses are involved in their etiology and symptomatology. In this regard, the bidirectional communication between neuroendocrine and immune system has been demonstrated to provide a homeostatic network that is involved in several pathological conditions. Adipokines represent a wide variety of bioactive, immune and inflammatory mediators mainly released by adipocytes that act as signal molecules in the neuroendocrine-immune interactions. Adipokines can also be synthesized by synoviocytes, osteoclasts, osteoblasts, chondrocytes and inflammatory cells in the joint microenvironment, showing potent modulatory properties on different effector cells in OA and RA pathogenesis. Effects of adiponectin, leptin, resistin and visfatin on local and systemic inflammation are broadly described. However, more recently, other adipokines, such as progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin, have been recognized to display immunomodulatory actions in rheumatic diseases. This review highlights the latest relevant findings on the role of the adipokine network in the pathophysiology of OA and RA.
31219668 A randomized study comparing regular care with a nurse-led clinic based on tight disease a 2019 Sep INTRODUCTION: A recent survey showed that 27% of rheumatoid arthritis (RA) patients had inadequately controlled disease activity. Hence, there is a need for new strategies aiming at improving patient outcomes. The aim of the present study was to evaluate the effect of a nurse-led clinic with frequent visits, treat-to-target and person-centred care of patients with established RA and moderate-to-high disease activity compared with patients receiving regular care. METHODS: The study was a randomized, controlled trial over 26 weeks, with a nonrandomized extension to week 50. Patients were randomized to an intervention group (IG; nurse-led clinic) based on person-centred care, frequent visits and "treat to target", or to a control group (CG) which visited the clinic according to care as usual. The primary outcome was the difference in the DAS28 change between the IG and the CG groups. RESULTS: A total of 332 patients were screened for eligibility, of which 70 were randomly assigned to either the IG (n = 36) or the CG (n = 34) group. The primary outcome was not met, although patients in the IG group tended to improve more than those in the CG group (difference: 0.43 (95% confidence interval [CI] -0.27, 1.13). In both the IG and CG groups, delta-DAS28 improved significantly. The European League Against Rheumatology moderate or good response was achieved by 76% (95% CI 58, 89) in the IG and 49% (95% CI 32, 65) in the CG group. CONCLUSIONS: Disease activity tended to improve more with the nurse-led intervention compared with regular care, although the difference was not significant, probably partly due to the lack of statistical power.
31122662 Health Care Resource Utilization and Costs Associated With Switching Biologics in Rheumato 2019 Jun PURPOSE: Although biologics are effective in managing rheumatoid arthritis (RA), many patients experience at least one biologic switch during treatment. A switch in biologic treatment can occur for medical or nonmedical reasons. Changes to treatment regimens, even in patients previously stable on therapy, can have clinical and cost implications. This study examined health care resource use and costs incurred with switching from an anti-tumor necrosis factor (TNF) medication in a population of patients with RA. METHODS: A retrospective analysis of patients with RA identified in Truven Commercial Claims and Encounters database (January 1, 2009, to December 13, 2013) was conducted. Patients were required to show evidence of new initiation of treatment with a biologic medication (index date) and continuous eligibility from 6 months before to 12 months after index. Patients were segmented into a continuous biologic group and a biologic switch group, the latter being further divided into switch from anti-TNF to anti-TNF (A-A subgroup) and switch from anti-TNF to a treatment with other mechanism of action (A-O subgroup). Means (SD) and medians of resource use and cost outcomes were calculated over the 12-month postindex period; multivariate models controlling for demographics, biologic switch, and preindex health, resource use, and costs were constructed. FINDINGS: The total sample comprised 18,070 patients, with 16,643 qualifying for the continuous group and 1427 qualifying for the overall switch group. The overall switch group was more likely to utilize physician office, emergency department, and pharmacy services compared to the continuous group. Consequently, the overall switch group incurred greater total health care costs compared to the continuous group ($41,482 vs $36,557 per patient per annum; p < 0.05). Within the switch group, the A-O subgroup had significantly greater outpatient, medical, and total health care expenditures compared to those in the A-A subgroup. Regression analyses revealed that increased baseline utilization and costs, worse health, and older age were associated with increased utilization and costs over the follow-up period. Switching of biologics was associated with an approximate increase of US $4000 per patient per annum in total health care costs. IMPLICATIONS: These findings suggest that switching biologic agents in patients with RA may be accompanied by increased total health care costs. Efforts to optimize patient response to initial biologic therapy and to reduce unnecessary switching, such as for nonmedical reasons, may help to mitigate these costs.
31758423 Iguratimod dose dependently inhibits the expression of citrullinated proteins and peptidyl 2020 Mar INTRODUCTION: Anti-citrullinated protein antibodies (ACPAs) play an important role in rheumatoid arthritis (RA). Citrullinated proteins (CPs), which are produced by post-translational modification via peptidylarginine deiminase (PAD), are the target antigen of ACPAs and promote the generation thereof. Herein, we investigated whether iguratimod (IGU) affects the generation of CPs via PAD. METHODS: Neutrophils and peripheral blood mononuclear cells (PBMCs) were isolated from three patients diagnosed with RA and treated with various concentrations of IGU, methotrexate (MTX), or dexamethasone (DXM) or without any drugs as a control for 8 h. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 in culture supernatants were tested by ELISA. CPs were measured by western blot, and the expression of PAD2 and PAD4 in cells was detected by qRT-PCR and western blot. RESULTS: PAD2 and PAD4 expressions in neutrophils but not in PBMCs were decreased by IGU at both the protein and mRNA levels (P < 0.05). CP expression in neutrophils but not in PBMCs was also inhibited by IGU. The inhibitory effect of IGU was dose-dependent. IGU, MTX, and DXM dose dependently decreased the secretion of TNF-α, IL-1β, IL-6, and IL-8 in neutrophils and PBMCs (P < 0.05); the inhibitory effect of IGU was not significantly different from that of MTX and DXM. CONCLUSIONS: IGU inhibited the expression of CPs by downregulating PADs in neutrophils from RA patients, and the effect was comparable to that of MTX and DXM at appropriate concentrations. These findings may provide guidance for more appropriate treatment of RA.Key Points• Iguratimod inhibited citrullinated protein expression in neutrophils from rheumatoid arthritis patients similarly to methotrexate and dexamethasone at appropriate concentrations.• The inhibitory effect was mediated by downregulation of peptidylarginine deiminases, providing insight into the mechanism of iguratimod as a treatment for rheumatoid arthritis.• This study may guide rheumatoid arthritis treatment and facilitate identification of other therapeutic targets.
31248587 The neutrophil-lymphocyte ratio in early rheumatoid arthritis and its ability to predict s 2019 Dec OBJECTIVES: To assess whether the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) can predict those who subsequently require escalation of disease modifying therapy because of continued disease activity in rheumatoid arthritis (RA). METHODS: Patients with newly diagnosed RA were recruited from the Early Arthritis Clinic at the Royal Adelaide Hospital. All patients commenced "triple-therapy" with a standardised protocol of methotrexate, sulfasalazine and hydroxychloroquine, and were reviewed every three to six weeks. DMARD therapy was adjusted according to a pre-defined algorithm if not in low disease activity. The NLR, PLR and other markers of disease activity including ESR, CRP and DAS28 were collected, as well as current therapy. The primary outcome measure was failure of triple-therapy to maintain low-disease activity (DAS28<3.2) at 12 months. RESULTS: Two-hundred and twenty-two patients met inclusion criteria. The mean age was 54.2 ± 15.4 years, with a mean disease duration of 22.3 ± 25.0 weeks. Forty-five (20%) patients had failed triple therapy by one year. The mean baseline NLR was significantly higher in those who failed triple therapy compared with those who did not (3.7 ± 2.8 vs. 2.9 ± 1.5; p = 0.02), however, the PLR was not significantly different. A baseline NLR>2.7 was an independent predictor of treatment failure (OR 2.65, CI 1.23-5.72, p = 0.01) whilst the PLR, ESR, CRP and DAS-28ESR were not. CONCLUSION: The NLR is significantly increased in those who subsequently fail triple-therapy for RA, and it outperformed conventional markers of disease activity. The NLR may offer an inexpensive, objective and reproducible prognostic marker in RA. Further studies are justified to confirm its potential role in guiding the management of RA.
31857078 Expression and methylation levels of suppressor of cytokine signaling 3 in rheumatic arthr 2020 Apr BACKGROUND: In the present study, we aimed to understand the expression and methylation levels of the suppressor of cytokine signaling 3 (SOCS3) in rheumatoid arthritis (RA) synovial fibroblasts. METHOD: The RA model was established using Freund's complete adjuvant, and then the synovial fibroblasts were isolated and cultured. Next, RNA extraction and reverse transcription were performed. The SOCS3 transcription level was detected using qPCR, and SOCS3 protein expression was detected using western blotting (WB). Lastly, methylation-specific PCR (MSP) was performed. RESULTS: The RA model was successfully demonstrated. SOCS3 gene (p < .01) and protein expression levels were significantly increased in the RA rat group compared to in the wild type (WT) group. However, no significant difference was observed in the MSP products between the RA and WT groups. CONCLUSION: The increased expression of the SOCS3 can be correlated with the development of RA.