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ID PMID Title PublicationDate abstract
28742141 Bruton's tyrosine kinase inhibitor BMS-986142 in experimental models of rheumatoid arthrit 2017 Bruton's tyrosine kinase (BTK) regulates critical signal transduction pathways involved in the pathobiology of rheumatoid arthritis (RA) and other autoimmune disorders. BMS-986142 is a potent and highly selective reversible small molecule inhibitor of BTK currently being investigated in clinical trials for the treatment of both RA and primary Sjögren's syndrome. In the present report, we detail the in vitro and in vivo pharmacology of BMS-986142 and show this agent provides potent and selective inhibition of BTK (IC50 = 0.5 nM), blocks antigen receptor-dependent signaling and functional endpoints (cytokine production, co-stimulatory molecule expression, and proliferation) in human B cells (IC50 ≤ 5 nM), inhibits Fcγ receptor-dependent cytokine production from peripheral blood mononuclear cells, and blocks RANK-L-induced osteoclastogenesis. Through the benefits of impacting these important drivers of autoimmunity, BMS-986142 demonstrated robust efficacy in murine models of rheumatoid arthritis (RA), including collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA). In both models, robust efficacy was observed without continuous, complete inhibition of BTK. When a suboptimal dose of BMS-986142 was combined with other agents representing the current standard of care for RA (e.g., methotrexate, the TNFα antagonist etanercept, or the murine form of CTLA4-Ig) in the CIA model, improved efficacy compared to either agent alone was observed. The results suggest BMS-986142 represents a potential therapeutic for clinical investigation in RA, as monotherapy or co-administered with agents with complementary mechanisms of action.
28780730 The Sesquiterpene Lactone, Budlein A, Inhibits Antigen-Induced Arthritis in Mice: Role of 2017 Dec Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by debilitating pain, cartilage destruction, and loss of joint function. Management of RA includes drugs that target NF-κB and downstream cytokine production. Therefore, molecules that act by inhibiting this signaling pathway without the severe side effects of, for instance, corticoids would be suitable therapeutic strategies. Budlein A is a sesquiterpene lactone with antinociceptive and anti-inflammatory properties related to the inhibition of pro-inflammatory cytokines and neutrophil recruitment. In this study, the effect of budlein A was evaluated in antigen-induced arthritis (AIA) in mice. At the 26th day, leukocyte recruitment to the knee joint, knee contents of proteoglycans, blood levels of ALT and AST, stomach tissue myeloperoxidase activity, and RT-qPCR for pro-inflammatory gene mRNA expression in knee joint samples was performed. NF-κB luciferase activity was evaluated in RAW 264.7 macrophages. Budlein A treatment dose-dependently inhibited AIA-induced mechanical hyperalgesia, edema, total leukocytes and neutrophil recruitment, and proteoglycan degradation. Budlein A did not induce gastric or liver damage. Budlein also inhibited AIA-induced Il-33, Tnf, Il-1β, preproET-1, and Cox-2 mRNA expression. In vitro, budlein reduced TNF- and IL-1β-induced NF-κB activity in RAW 264.7 macrophages. Altogether, we demonstrate that budlein A ameliorates AIA-induced inflammation and pain by targeting NF-κB. Importantly, budlein A does not induce in vivo side effects, suggesting that it possesses a favorable pre-clinical profile as analgesic and it is a prosperous molecule to be further investigated for the treatment of RA.
29435360 Real-world predictors of 12-month intravenous abatacept retention in patients with rheumat 2017 INTRODUCTION: An understanding of real-world predictors of abatacept retention is limited. We analysed retention rates and predictors of abatacept retention in biologic-naïve and biologic-failure patients in a 12-month interim analysis of the 2-yearAbataCepTIn rOutiNe clinical practice (ACTION) study. METHODS: ACTION was an international, observational study of patients with moderate-to-severe rheumatoid arthritis (RA) who initiated intravenous abatacept. In this 12-month interim analysis, crude abatacept retention rates, predictors of retention and European League Against Rheumatism (EULAR) response were evaluated in both biologic-naïve and biologic-failure patients. Retention by rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) status was also assessed, in patients with or without baseline radiographic erosions, and by body mass index (BMI). RESULTS: Overall, 2350/2364 enrolled patients were evaluable (674 biologic naїve; 1676 biologic failure). Baseline characteristics were largely similar in biologic-naïve and biologic-failure groups. Crude retention rates (95% CI) at 12 months were significantly higher in biologic-naїve (78.1%(74.7% to 81.2%)) versus biologic-failure patients (69.9%(67.6% to 72.1%); P<0.001). RF/anti-CCP double positivity predicted higher retention in both patient groups, and remained associated with higher retention in patients with erosive disease. BMI did not impact abatacept retention in either patient group, irrespective of RF/anti-CCP serostatus. Good/moderate EULAR response rate at 12 months was numerically higher in biologic-naїve (83.8%) versus biologic-failure (73.3%) patients. There were no new safety signals. CONCLUSION: High levels of intravenous abatacept retention in clinical practice were confirmed, particularly in biologic-naïve patients, including in those with poor RA prognostic factors. Retention was unaffected by BMI, regardless of RF/anti-CCP serostatus. TRIAL REGISTRATION NUMBER: NCT02109666; retrospectively registered 8 April 2014.
28270300 Advances in Mouse Models of Sjögren's Syndrome. 2017 Feb 20 Sjögren's syndrome (SS) is a common chronic systemic autoimmune disease;however,its pathogenic mechanisms remain unclear. Proper mouse models of SS are essential for experiments. This article summarizes the recent advances in spontaneous mouse models of SS,genetically engineered mouse models of SS,and experimentally induced mouse models of SS.
28483646 Review: MicroRNAS in ocular surface and dry eye diseases. 2017 Oct Since the first description of microRNAs (miRNAs) in the 1990s, more than 60 papers have described the role of miRNAs on the ocular surface and lacrimal gland (LG). MicroRNAs (miRNAs) have a role in several physiological events and in mediation of disease. They inhibit gene expression by blocking messenger RNA. Diseases such as Sjögren syndrome (SS), ocular surface neoplasias, and infections are known to increase or reduce the expression of specific miRNAs. These miRNAs play key roles in modulating inflammation, delaying or enhancing wound healing, cell differentiation metabolism, and survival. This review describes the current understanding of miRNAs as biomarkers, mediators of diseases, and potential therapeutic targets in ocular surface diseases.
29296125 Dose Escalation and Co-therapy Intensification Between Etanercept, Adalimumab, and Inflixi 2017 OBJECTIVE: To compare anti-TNF dose escalation, DMARD and/or glucocorticoid intensification, switches to another biologic, and drug and drug-related costs over 12 and 18 months for rheumatoid arthritis (RA) patients initiating etanercept (ETN), adalimumab (ADA), or infliximab (IFX) in routine clinical practice across Canada. METHODS: A retrospective chart review of biologic-naïve adult RA patients newly initiating ADA, ETN, or IFX between January 01, 2006 and December 31, 2012 from 11 practices across Canada. RESULTS: There were 314 patients in the 12-month analysis and 217 in the 18-month analysis. No dose escalation occurred with ETN over 12 and 18 months versus 38% and 32% for IFX (p<0.001) and 2% and 2% for ADA (p=0.199, p=0.218). Over 18 months, dose escalation and/or DMARD and/or glucocorticoid intensification was less frequent among ETN (16%) versus IFX (44%, p=0.005) and ADA (34%, p=0.004). By 18 months, 22% of patients initiating ADA had switched to another biologic compared with 6% of ETN patients (p=0.001).Patients initiating ETN had lower total (drug and drug-related) costs over 12 and 18 months compared to IFX, and no difference compared to ADA when adjusted for potential confounders. Patients with dose escalation had higher costs compared to those with no dose escalation. CONCLUSION: Physicians were more likely to escalate the dose of IFX, but optimize co-therapy with ADA and ETN. ETN patients had no dose escalation and were less likely to have DMARD and/or glucocorticoid intensification than ADA patients. ETN-treated patients had lower costs compared to IFX patients.
28256007 Targeting Notch-Activated M1 Macrophages Attenuates Joint Tissue Damage in a Mouse Model o 2017 Jul Expression levels of Notch signaling molecules are increased in synovium from patients with rheumatoid arthritis (RA). However, it is not known which cell type(s) in RA synovium have Notch activation or if they play a pathogenetic role in RA. Here, we used Hes1-GFP/TNF-transgenic (TNF-Tg) mice to investigate the role of cells with active Notch signaling (GFP+) in RA. The number of GFP+ cells was significantly increased in synovium in Hes1-GFP/TNF-Tg mice and about 60% of them were F4/80+ macrophages expressing the inflammatory macrophage (M1) marker. TNF-Tg mice transplanted with Hes1-GFP/TNF-Tg bone marrow (BM) had significantly more GFP+ cells in their synovium than in BM. Intraarticular injection of Hes1-GFP/TNF-Tg or Hes1-GFP+ BM macrophages into WT and TNF-Tg mice showed the highest synovial GFP+ cells in the TNF-Tg mice that received Hes1-GFP/TNF-Tg cells. Thapsigargin (THAP), a Notch inhibitor, decreased TNF-induced M1 and increased M2 numbers and reduced joint lesion, synovial M1s, and GFP+ cells in Hes1-GFP/TNF-Tg mice. THAP did not affect M1s from mice carrying a constitutively active Notch1. Thus, the main cells with activated Notch signaling in the inflamed synovium of TNF-Tg mice are M1s derived from BM and targeting them may represent a new therapeutic approach for patients with inflammatory arthritis. © 2017 American Society for Bone and Mineral Research.
26222375 Anti-inflammatory and anti-arthritic activity of aqueous extract of Rosa centifolia in exp 2017 Sep AIM: The present study was carried out to evaluate the anti-inflammatory and antiarthritic activity of Rosa centifolia aqueous extract (RC) in a carrageenan-induced paw edema model and complete Freund's adjuvant (CFA)-induced arthritis. METHODS: Anti-inflammatory activity of RC was evaluated using the carrageenan-induced paw edema model in rats. Arthritis was induced in rats by sub-plantar administration of CFA. Joint size was measured at regular intervals by using a micrometer screw gauge. Serum and ankle joints of rats immunized with CFA were collected and subjected to enzyme-linked immunosorbent assay for estimation of tumor necrosis factor (TNF)-α level and dot blot for secretory cytokines interleukin (IL)-1β and IL-6. An acute and 28-day oral toxicity study was carried out to evaluate the safety of the test drug. RESULTS: Pre-treatment with RC produced a dose-dependent reduction in carrageenan-induced paw edema and CFA-induced arthritis models and was effective as indomethacin. RC also inhibited the delayed increase in joint diameter as seen in control and indomethacin-treated animals in CFA-induced arthritis. The expression of proinflammatory mediators TNF-α, IL-6 and IL-1β was also found to be less in the RC-treated group as compared to controls. CONCLUSION: Based on these results, it was suggested that Rosa centifolia could be considered as a potential anti-inflammatory and anti-arthritic agent.
28243468 Baseline autoantibodies preferentially impact abatacept efficacy in patients with rheumato 2017 OBJECTIVES: To determine the impact of baseline rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) status on the clinical efficacy of intravenous abatacept in biologic-naïve patients with rheumatoid arthritis (RA) enrolled in the real-world ACTION study. METHODS: Clinical outcomes (European League Against Rheumatism (EULAR) response, mean Clinical Disease Activity Index (CDAI) and Boolean remission) at 6 months were compared by baseline RF and anti-CCP status. RESULTS: Of 672 biologic-naïve patients, RF status was reported in 577 (86%) (412 (71%) positive) and anti-CCP status in 552 (82%) (364 (66%) positive); of 511 patients for whom data were available, 308/511 (60%) were double positive and 127/511 (25%) were double negative. Clinical outcomes were improved with RF-positive or anti-CCP-positive versus RF-negative/anti-CCP-negative status-good or moderate EULAR response: RF: 84.6 vs 72.9%, p=0.012; anti-CCP: 85.2 vs 74.2%, p=0.015; mean CDAI (calculated): RF: 10.8 vs 15.3, p<0.001; anti-CCP: 10.9 vs 14.3, p=0.002; and Boolean remission: RF: 13.3 vs 4.0%, p=0.008; anti-CCP: 12.5 vs 6.3%, p=0.096. Clinical outcomes were also improved with single or double RF-positive/anti-CCP-positive versus double-negative status. CONCLUSIONS: In biologic-naïve patients with RA, RF-positive and/or anti-CCP-positive status is associated with greater efficacy of intravenous abatacept than seronegative status. TRIAL REGISTRATION NUMBER: NCT02109666.
34760473 Shear-wave elastographic ultrasound of metacarpophalangeal synovium in rheumatoid arthriti 2017 May INTRODUCTION: Shear-wave elastographic ultrasound (SW-EUS) assesses the stiffness of human tissues. It is used in liver, thyroid and breast imaging but has not been studied in synovium. Soft tissues have a slower shear-wave velocity (SWV) than stiff tissues. We hypothesised that rheumatoid arthritis (RA) patients would have softer synovium than controls and this could be quantified with a slower SWV. We also assessed whether SWV varied with disease activity. METHODS: Nine patients with RA were consecutively recruited and matched with five controls. Participants underwent clinical assessment, blood sampling, grey scale ultrasound (GSUS), power Doppler ultrasound and SW-EUS of MCP joints 2-5 on the dominant hand. RESULTS: Average age was 60. Mean RA disease activity (DAS28-ESR) was moderate at 3.65. Patients with RA had lower maximum synovial SWV than controls (6.38 m/s vs. 6.99 m/s P = 0.042). Negative Pearson's correlation coefficients (PCC) were observed between maximum SWV and disease activity markers including GSUS graded synovial thickness (PCC = -0.57, P = 0.03) and ESR (PCC = -0.46, P = 0.095). Intra- and interobserver reliability was good with intraclass correlation coefficients (ICC) of 0.66 and 0.58, respectively, for quantitative maximum SWV and ICC > 0.80 for colour scale rated SWV. CONCLUSION: This is the first pilot study of SW-EUS in synovium. Maximum synovial SWV was significantly lower in RA than controls. There was a negative correlation between maximum SWV and GSUS synovial thickening. Further study is warranted to confirm the role of SW-EUS in diagnosing and assessing disease activity in RA.
29387286 Long-Term Outcomes in Puerto Ricans with Rheumatoid Arthritis (RA) Receiving Early Treatme 2017 BACKGROUND: Early treatment of rheumatoid arthritis (RA) results in better long-term outcomes. However, the optimal therapeutic window has not been clearly established. OBJECTIVE: To determine the clinical outcome of Puerto Ricans with RA receiving early treatment with conventional and/or biologic disease-modifying anti-rheumatic drugs (DMARDs) based on the American College of Rheumatology (ACR) definition of early RA. METHODS: A cross-sectional study was performed in a cohort of Puerto Ricans with RA. Demographic features, clinical manifestations, disease activity, functional status, and pharmacotherapy were determined. Early treatment was defined as the initiation of DMARDs (conventional and/or biologic) in less than 6 months from the onset of symptoms attributable to RA. Patients who received early (< 6months) and late (≥6 months) treatments were compared using bivariate and multivariate analyses. RESULTS: The cohort comprised 387 RA patients. The mean age at study visit was 56.0 years. The mean disease duration was 14.9 years and 337 (87.0%) patients were women. One hundred and twenty one (31.3%) patients received early treatment. In the multivariate analysis adjusted for age and sex, early treatment was associated with better functional status, lower probability of joint deformities, intra-articular injections and joint replacement surgeries, and lower scores in the physician's assessments of global health, functional impairment and physical damage of patients. CONCLUSION: Using the ACR definition of early RA, this group of patients treated with DMARDs within 6 months of disease had better long-term outcomes with less physical damage and functional impairment.
28790807 Non-persistence and non-adherence to MTX therapy in patients with rheumatoid arthritis: a 2017 OBJECTIVE: This study aimed to assess the level of nonpersistence (NP) and nonadherence (NA) to methotrexate (MTX) therapy in German patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: Based on German claims data, RA patients who received a MTX therapy (subgroup: treatment-naive patients) were analyzed. NP was defined as treatment gap >12 weeks. Regarding NA, it is the overall medication possession ratio (MPR) during an observational period of 12 or 24 months after therapy, and the MPR is calculated only for the periods of therapy continuation; NA was defined as MPR <80%. RESULTS: A total of 7,146 RA patients who received at least one MTX prescription (subgroup: 1,211 treatment-naive patients) could be observed (mean age: 64.4 years, 73.6% female). Percentage of NP patients among MTX-naive patients after 6, 12 and 18 months was 16.7%, 34.0% and 36.7%, respectively. After MTX therapy discontinuation, 39.9% had restarted their MTX therapy, 13.8% had received another non-MTX synthetic disease-modifying antirheumatic drug (sDMARD), 8.1% had biological DMARD (bDMARD) and 49.2% had not received any DMARD prescription at all. Overall, 12- and 24-month MPRs for MTX therapy were 83.0% and 76.5% with a percentage of NA patients of 25.8% and 33.8%, respectively. During periods of general treatment continuation, the percentage of patients with an MPR <80% was 6.5%. CONCLUSION: NP to MTX treatment seems to be common in one-fourth of German patients with RA. An additional number of patients, at least 6.5%, are also affected by NA. A considerable percentage of RA patients who discontinued MTX therapy do not receive any follow-up DMARD therapy.
28243133 Determinants of biological drug survival in rheumatoid arthritis: evidence from a Hungaria 2017 OBJECTIVE: To compare drug survival of biological therapies in patients with rheumatoid arthritis (RA), and analyze the determinants of discontinuation probabilities and switches to other biological therapies. MATERIALS AND METHODS: Consecutive RA patients initiating first biological treatment in one rheumatology center between 2006 and 2013 were included. Log-rank test was used to analyze the differences between the survival curves of different biological drugs. Cox regression was applied to analyze the discontinuation due to inefficacy, the occurrence of adverse events, or to any reasons. RESULTS: A total of 540 patients were included in the analysis. The most frequently used first-line biological treatments were infliximab (N=176, 33%), adalimumab (N=150, 28%), and etanercept (N=132, 24%). Discontinuation of first tumor necrosis factor-alpha (TNF-α) treatment was observed for 347 (64%) patients, due to inefficacy (n=209, 60%), adverse events (n=103, 30%), and other reasons (n=35, 10%). Drug survival rates for TNF-α and non-TNF-α therapies were significantly different, and were in favor of non-TNF-α therapies. Every additional number of treatment significantly increased the risk of inefficacy by 27% (p<0.001) and of adverse events by 35% (p=0.002). After the discontinuation of the initial TNF-α treatment, switching to rituximab and tocilizumab was associated with significantly longer treatment duration than switching to a second TNF-α. The non-TNF-α therapies resulted in significantly longer treatment duration, due to both less adverse events and longer maintenance of effectiveness. CONCLUSION: Non-TNF-α therapies resulted in significantly longer treatment duration, and lost their effectiveness later. Increase in the number of switches significantly increased the risk of discontinuation of any biological therapy.
28053549 Persistence, switch rates, drug consumption and costs of biological treatment of rheumatoi 2017 OBJECTIVES: The aim of this analysis was to provide an estimate of drug utilization indicators (persistence, switch rate and drug consumption) on biologics and the corresponding costs (drugs, admissions and specialist care) incurred by the Italian National Health Service in the management of adult patients with rheumatoid arthritis (RA). METHODS: We conducted an observational retrospective cohort analysis using the administrative databases of three local health units. We considered all patients aged ≥18 years with a diagnosis of RA and at least one biologic drug prescription between January 2010 and December 2012 (recruitment period). Persistence was defined as maintenance over the last 3 months of the follow-up period of the same biological therapy administered at the index date. A switch was defined as the presence of a biological therapy other than that administered at the index date during the last 3 months of the follow-up period. Hospital admissions (with a diagnosis of RA or other RA-related diagnoses), specialist outpatient services, instrumental diagnostics and pharmaceutical consumption were assessed. RESULTS: The drug utilization analysis took into account only biologics with at least 90 patients on treatment at baseline (adalimumab n=144, etanercept n=236 and infliximab n=94). In each year, etanercept showed better persistence with initial treatment than adalimumab or infliximab. Etanercept was characterized by the lowest number of patients increasing the initial drug consumption (2.6%) and by the highest number of patients reducing the initial drug consumption (10.5%). The mean cost of treatment for a patient persisting with the initial treatment was €12,388 (€14,182 for adalimumab, €12,103 for etanercept and €11,002 for infliximab). The treatment costs for patients switching from initial treatment during the first year of follow-up were higher than for patients who did not switch (€12,710 vs. €11,332). CONCLUSION: Persistence, switch rate and drug consumption seem to directly influence treatment costs. In subjects not persisting with initial treatment, other health care costs were approximately three times higher than for persistent patients. This difference could suggest a positive effect on the quality of life for persistent patients. Etanercept showed the highest persistence with treatment.
30886949 The underrated prevalence of depression in Japanese patients with rheumatoid arthritis - e 2017 BACKGROUND: To determine the prevalence of depression among Japanese people with rheumatoid arthritis (RA) and explore the relationships between depression and an array of variables. METHODS: Nation-wide, cross-sectional online survey (n = 500) of people with RA including the Patient Health Questionnaire (PHQ-9) to measure the presence and severity of depressive symptoms were performed. RESULTS: While only 5% of the population studied had been officially diagnosed with depression, 35% had PHQ-9 scores indicating depression was present. People with RA are more likely to experience depression if they are younger, have greater functional impairment, or whose treatment regimen includes pain medications not biologic agents. CONCLUSIONS: It is a potential risk of under-diagnosis and under-reporting of depression in Japanese people with RA. People with RA are more likely to experience depression if they are younger, have greater functional impairment, or whose treatment regimen includes pain medications without biologic drugs.
28878854 Composite Cutaneous Lymphoma (Iatrogenic Immunodeficiency-Associated Lymphoproliferative D 2017 Sep A 67 year old woman with a 10 year history of rheumatoid arthritis (RA) treated with methotrexate and prednisone, presented with a 2 year history of worsening multiple cutaneous plaques of variable appearance. Two distinct skin lesions were biopsied to reveal a composite cutaneous lymphoma, possibly caused by long term methotrexate therapy. An [18F] fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) was performed to stage the malignancy, and was later repeated to evaluate response to chemotherapy, which guided subsequent management. We present the PET/CT imaging findings of this very rare iatrogenic (methotrexate induced) immunodeficiency-associated lymphoproliferative disorder.
28860771 Moderating role of self-efficacy on the associations of social support with depressive and 2017 PURPOSE: Rheumatoid arthritis (RA) is significantly associated with depression and anxiety. Social support and self-efficacy are the coping resources of psychological distress. However, little research is available on the interaction of social support and self-efficacy in RA patients. This study aimed to identify the prevalence of depressive and anxiety symptoms and to examine whether or not self-efficacy moderates the associations of social support with depressive and anxiety symptoms in Chinese RA patients. METHODS: A multicenter, cross-sectional study was conducted in northeast of China from December 2014 to January 2016. A total of 297 RA patients completed the Center for Epidemiologic Studies Depression Scale, Zung Self-Rating Anxiety Scale, Multidimensional Scale of Perceived Social Support and General Self-Efficacy Scale. The associations of social support, self-efficacy and social support × self-efficacy interaction with depressive and anxiety symptoms were examined by hierarchical regression analysis. If the interaction was statistically significant, simple slope analysis was conducted. RESULTS: The prevalence of depressive symptoms was 58.2%, while 47.5% RA patients had anxiety symptoms. Social support and social support × self-efficacy interaction were significantly associated with depressive symptoms. Social support, self-efficacy and their interaction were significantly associated with anxiety symptoms. The association between social support and depressive symptoms was gradually reduced in the low (1 standard deviation [SD] below the mean, B=-0.614, β=-0.876, P<0.001), mean (B=-0.395, β=-0.563, P<0.001) and high (1 SD above the mean, B=-0.176, β=-0.251, P=0.002) groups of self-efficacy. For anxiety symptoms, the association was also gradually reduced in the low (B=-0.527, β=-0.774, P<0.001), mean (B=-0.288, β=-423, P<0.001) and high (B=-0.049, β=-0.071, P=0.447) groups of self-efficacy. CONCLUSION: There was a high prevalence of depressive and anxiety symptoms in Chinese RA patients. Self-efficacy could attenuate the associations of social support with depressive and anxiety symptoms. Adequate social support and self-efficacy intervention should be provided to alleviate psychological distress.
29299482 Have the annual trends of total hip arthroplasty in rheumatoid arthritis patients decrease 2017 Dec BACKGROUND: Rheumatoid arthritis (RA) is characterized by chronic systemic and synovial inflammation, resulting in damage to both cartilage and bone. Medical treatment, which has increasingly relied upon disease modifying anti-rheumatic drugs (DMARDs), may fail to slow disease progression and limit joint damage, ultimately warranting surgical intervention. Up to 25% of RA patients will require lower extremity total joint arthroplasty. Though total hip arthroplasty (THA) is known to improve quality of life and functional measures, clarification is still required with respect to the impact of increased DMARD use on annual rates of THA. Thus, the purpose of this study was to evaluate: (I) the annual trends of THAs due to RA in the United States population; (II) the annual trends in the proportion of THAs due to RA in the United States. METHODS: This study utilized the Nationwide Inpatient Sample (NIS) to identify all patients who underwent THA between 2002 and 2013 (n=3,135,904). Then, THA patients who had a diagnosis of RA, which was defined by the International Classification of Disease 9(th) revision diagnosis code 714.0, were identified. The incidence of THAs with a diagnosis of RA in the United States was calculated using the United States population as the denominator. Regression models were used to analyze the annual trends of RA in patients who underwent THA. RESULTS: Review of the database identified 90,487 patients who had a diagnosis of RA and underwent THA from 2002 to 2013. The annual prevalence of RA in those who underwent THA slightly decreased over the specified time period, with 28.7 per 1,000 THAs in 2002 and 28.6 per 1,000 THAs in 2013; however, this change was not statistically significant (R(2)=0.158, P=0.200). CONCLUSIONS: The annual rates of THA among RA patients did not show any significant change between 2002 and 2013. DMARD use has decreased both disease progression and joint destruction, and DMARDs are now often utilized as primary treatment. The increase in population of the country during the study period may have overestimated THA trends. Moreover, patients may be more likely to opt for surgical management, given the advances in operative techniques as well as peri- and post-operative course.
29204858 A Retrospective Analysis of Corticosteroid Utilization Before Initiation of Biologic DMARD 2018 Jun INTRODUCTION: Understanding the effects of corticosteroid utilization prior to initiation of biologic disease-modifying antirheumatic drugs (DMARDs) can inform decision-makers on the appropriate use of these medications. This study examined treatment patterns and associated burden of corticosteroid utilization before initiation of biologic DMARDs among rheumatoid arthritis (RA) patients. METHODS: A retrospective analysis was conducted of adult RA patients in the US MarketScan Database (2011-2015). The following patterns of corticosteroid utilization were analyzed: whether corticosteroids were used; duration of use (short/long duration defined as < or ≥ 3 months); and dosage (low as < 2.5, medium as 2.5 to < 7.5 and high as ≥ 7.5 mg/day). Effects of corticosteroid use on time to biologic DMARD initiation were examined using Cox proportional hazards models. Likelihood and number of adverse events were examined using logistic and negative binomial regression models. Generalized linear models were used to examine healthcare costs. Independent variables in all models included patient demographics and health characteristics. RESULTS: A total of 25,542 patients were included (40.84% used corticosteroids). Lower hazard of biologic DMARD initiation was associated with corticosteroid use (hazard ratio = 0.89, 95% confidence interval = 0.83-0.96), long duration and lower dose. Corticosteroid users compared to non-users had higher incidence rates of various adverse events including cardiovascular events (P < 0.05). Higher likelihood of adverse events was associated with corticosteroid use and long duration of use, as was increased number of adverse events. Corticosteroid users had a greater annualized mean number of physician visits, hospitalizations, and emergency department (ED) visits than non-users in adjusted analysis. Corticosteroid users compared to non-users had higher mean costs for total healthcare, physician visits, hospitalizations, and ED visits. CONCLUSIONS: Among patients with RA, corticosteroid utilization is associated with delayed initiation of biologic DMARDS and higher burden of adverse events and healthcare utilization/costs before the initiation of biologic DMARDs. FUNDING: AbbVie Inc.
30375525 Prevalence of Metabolic Syndrome in Treatment Naïve Rheumatoid Arthritis and Correlation 2017 Mar OBJECTIVES: This study aims to assess the prevalence of metabolic syndrome (MetS) in treatment naïve rheumatoid arthritis (RA) in an Indian population and correlate RA disease characteristics with presence of MetS. PATIENTS AND METHODS: The study included 84 RA patients (18 males, 66 females; mean age 44.8±12.5 years; range 18 to 72 years) diagnosed according to 2010 American College of Rheumatology-European League Against Rheumatism classification criteria who were treatment naïve or did not receive disease modifying antirheumatic drugs for more than six weeks and 120 age and sex-matched apparently healthy controls (35 males, 85 females; mean age 44.1±12.7 years; range 18 to 75 years). The frequency of MetS was assessed using National Cholesterol Education Program- Adult Treatment Panel III 2004 revised criteria. Patients were also assessed in terms of disease activity, using disease activity score 28 erythrocyte sedimentation rate. Logistic regression was used to identify predictors of MetS in RA. RESULTS: Metabolic syndrome was found in 39.28% of RA group and 20% of control group according to National Cholesterol Education Program- Adult Treatment Panel III 2004 (p<0.005). MetS was most commonly detected in the 51 to 60 age group (65%). RA group was significantly more likely to have low high-density lipoprotein (63.09%), high triglyceride (53.57%), elevated blood pressure (41.66%) levels, and elevated waist circumference (38.09%). In RA group, disease activity score 28 (odds ratio: 6.51, confidence interval: 1.19-35.46 p=0.03), C-reactive protein (odds ratio: 1.13, confidence interval: 1.05-1.21 p<0.001), and duration of disease (odds ratio: 1.82, confidence interval: 1.04-3.18 p=0.03) remained independent predictors for presence of MetS in RA. CONCLUSION: The frequency of MetS was higher in RA group compared to control group. Higher systemic inflammatory marker, disease duration, and disease activity score 28 remained independent predictors associated with presence of MetS. These findings suggest that RA patients should be screened early for presence of MetS to check for and reduce risk of atherosclerotic vascular diseases.