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ID PMID Title PublicationDate abstract
26141704 Emerging molecules in the interface between skeletal system and innate immunity. 2015 Sep Despite the improved treatment of bone destruction, significant unmet medical need remains. For example, there is a limited benefit of continued bisphosphonate therapy for osteoporotic patients, and only minor populations of rheumatoid arthritis patients obtain biologic-free remission. Therefore, the identification of a novel therapeutic target for bone destructive diseases remains an important issue in the field of skeletal biology. To date there has been little progress in identifying osteo-innate-immunological regulators that could be used for the prophylactic treatment of inflammatory bone destruction. Recently, we identified several new molecules that are critical osteo-innate-immunological regulators by using gene targeting technology. These findings may offer an invaluable opportunity to regulate bone-destructive diseases, such as osteoporosis and rheumatoid arthritis.
28031164 Improvement in 5-year mortality in incident rheumatoid arthritis compared with the general 2017 Jun OBJECTIVE: Excess mortality in rheumatoid arthritis (RA) is expected to have improved over time, due to improved treatment. Our objective was to evaluate secular 5-year mortality trends in RA relative to general population controls in incident RA cohorts diagnosed in 1996-2000 vs 2001-2006. METHODS: We conducted a population-based cohort study, using administrative health data, of all incident RA cases in British Columbia who first met RA criteria between January 1996 and December 2006, with general population controls matched 1:1 on gender, birth and index years. Cohorts were divided into earlier (RA onset 1996-2000) and later (2001-2006) cohorts. Physician visits and vital statistics data were obtained until December 2010. Follow-up was censored at 5 years to ensure equal follow-up in both cohorts. Mortality rates, mortality rate ratios and HRs for mortality (RA vs controls) using proportional hazard models adjusting for age, were calculated. Differences in mortality in RA versus controls between earlier and later incident cohorts were tested via interaction between RA status (case/control) and cohort (earlier/later). RESULTS: 24 914 RA cases and controls experienced 2747 and 2332 deaths, respectively. Mortality risk in RA versus controls differed across incident cohorts for all-cause, cardiovascular diseases (CVD) and cancer mortality (interactions p<0.01). A significant increase in mortality in RA versus controls was observed in earlier, but not later, cohorts (all-cause mortality adjusted HR (95% CI): 1.40 (1.30 to 1.51) and 0.97 (0.89 to 1.05), respectively). CONCLUSIONS: In our population-based incident RA cohort, mortality compared with the general population improved over time. Increased mortality in the first 5 years was observed in people with RA onset before, but not after, 2000.
25752887 An update on the role of omega-3 fatty acids on inflammatory and degenerative diseases. 2015 Jun Inflammation is involved in the pathophysiology of many chronic diseases, such as rheumatoid arthritis and neurodegenerative diseases. Several studies have evidenced important anti-inflammatory and immunomodulatory properties of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs). This review illustrates current knowledge about the efficacy of n-3 LC-PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), particularly) in preventing and/or treating several chronic inflammatory conditions (inflammatory bowel diseases and rheumatoid arthritis) as well as their potential benefits on neurodegenerative diseases. It is well established that n-3 LC-PUFAs are substrates for synthesis of novel series of lipid mediators (e.g., resolvins, protectins, and maresins) with potent anti-inflammatory and pro-resolving properties, which have been proposed to partly mediate the protective and beneficial actions of n-3 LC-PUFAs. Here, we briefly summarize current knowledge from preclinical studies analyzing the actions of EPA- and DHA-derived resolvins and protectins on pathophysiological models of rheumatoid arthritis, Alzheimer, and irritable bowel syndrome.
26814681 Medication Persistence of Disease-Modifying Antirheumatic Drugs and Anti-Tumor Necrosis Fa 2016 Oct OBJECTIVE: To assess the use and persistence of anti-tumor necrosis factor (anti-TNF) versus disease-modifying antirheumatic drug (DMARD) therapies in patients with rheumatoid arthritis (RA) in Brazil. METHODS: This was a new-user cohort study of RA patients from 2003 to 2010, using administrative data. Individuals were classified as being persistent using a drug at the first year and the first 2 years after cohort entry, if they did not discontinue that drug during that period. Cox regression was used to identify potential determinants of discontinuation of therapy in each medication group. RESULTS: Among 76,351 patients, 14,313 were using anti-TNF (+/- DMARD) therapy. At the end of the first year of followup, 48.2% continued using anti-TNF (+/- DMARD) therapy compared to 42.6% who persisted with DMARDs only. At the end of the second year, 23.1% of anti-TNF (+/- DMARD) users and 19.3% of DMARD-only users continued with therapy. Infliximab users had the lowest persistence rates. Multivariate Cox regression analysis showed that among anti-TNF (+/- DMARD) users, higher discontinuation rates were observed in female patients, in patients with lower income (only at the first 2 years of followup), in nonresidents of the region with the highest Human Development Index (HDI) rates, in those with a higher comorbidity score, and in those enrolled in the 2003-2006 period. Among DMARD-only users, younger patients, patients with lower income, nonresidents in regions with high HDI, those with a higher comorbidity score, and those enrolled in the 2003-2006 period were also more likely to discontinue therapy. CONCLUSION: Brazilian patients with RA showed low rates of medication persistence for DMARDs and anti-TNF agents, particularly at the first 2 years of followup. Future work could determine what other factors might contribute to drug persistence in RA.
27086948 Prothrombotic biomarkers in patients with rheumatoid arthritis: the beneficial effect of I 2016 May OBJECTIVES: The pro-inflammatory cytokine interleukin (IL)-6 is involved in the pathogenesis of both rheumatoid arthritis (RA) and cardiovascular events. We evaluated the correlation of prothrombotic biomarkers, in particular those of thrombin generation, with inflammatory and clinical parameters in RA patients treated with tocilizumab, an IL-6 receptor (IL-6R) inhibitor. Naïve and maintenance patients were compared. METHODS: We studied 15 RA patients undergoing tocilizumab infusions at a University Outpatient Clinic. Eight received tocilizumab for the first time and were evaluated at baseline. Seven were in maintenance therapy (9 to 77 months). All 15 patients were evaluated four weeks after the last administration of tocilizumab. At each time, we assessed disease activity score 28 (DAS28), erythrocyte sedimentation rate (ESR) and plasma levels of C-reactive protein (CRP), IL-6, soluble (s)IL-6R, tumour necrosis factor-alpha (TNF-alpha), prothrombin fragment F1+2 and fibrin fragment D-dimer. Forty healthy subjects served as basal controls. RESULTS: At baseline, RA patients showed a moderate-to-high disease activity and median ESR of 51 mm/1(st) hour (interquartile range 25-63). Plasma levels of CRP (p=0.0001), IL-6 (p=0.043), sIL-6R (p=0.003), TNF-alpha (p=0.0001), F1+2 (p=0.0001) and D-dimer (p=0.002) were higher than those of healthy controls. After four weeks we observed reduction of DAS28 (p=0.0001), ESR (p=0.0001), CRP (p=0.014), TNF-alpha (p=0.006), F1+2 (p=0.009) and D-dimer (p=0.04). No differences were observed between naïve and maintenance patients. CONCLUSIONS: The reduction of prothrombotic biomarkers parallels the reduction of inflammatory parameters and clinical symptoms in RA patients treated with tocilizumab, both four weeks after the first administration and during maintenance therapy.
25939484 Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of 2016 Apr At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.
26912147 The frequency of and risk factors for osteoporosis in Korean patients with rheumatoid arth 2016 Feb 24 BACKGROUND: The aim of this study was to investigate the prevalence of osteoporosis in rheumatoid arthritis (RA) patients and to analyze the risk factors in these patients using the KORean Observational study Network for Arthritis (KORONA) database. METHODS: Among the RA patients in the KORONA who were recruited between July 2009 and December 2011, postmenopausal women with bone mineral density (BMD) results within one year from the time of KORONA enrollment were included in this study. The baseline characteristics of patients in three groups, defined by BMD results, were compared. The BMD measurement rates and prevalence of osteoporosis in the study patients were calculated in accordance with age and gender subgroups. Multivariable logistic regression analysis was used to explore the association between osteoporosis and demographics and disease-related risk factors. RESULTS: Of 1322 postmenopausal woman patients with RA in whom BMD was measured within one year of study enrollment, 619 patients (46.8 %) were in the osteoporosis group (T-score ≤ -2.5 SD). RA patients with osteoporosis had a higher frequency of previous fractures than those in other groups, especially fractures of the femur (p = 0.004) and wrist (p = 0.042). Advanced age (≥70 years; OR = 2.28, 95 % CI: 1.40-3.58), lower body mass index (<25; OR = 2.14, 95 % CI:1.52-3.02), longer disease duration (≥10 years; OR = 1.46, 95 % CI: 1.07-2.00), higher cumulative glucocorticoid dose (OR = 1.03, 95 % CI: 1.01-1.05), and higher Health Assessment Questionnaire score (OR = 1.37, 95 % CI:1.11-1.69) were independent risk factors for osteoporosis. CONCLUSION: A large percentage (90.8 %) of RA patients enrolled in the KORONA cohort had osteoporosis and osteopenia. Nevertheless, BMD measurement rates in this population remained low, despite high risk groups of fractures.
27749220 Treatment with the first TNF inhibitor in rheumatoid arthritis patients in the Hellenic Re 2016 Nov OBJECTIVES: To assess in daily practice in patients with rheumatoid arthritis (RA) the effect of treatment with first tumour necrosis factor-α inhibitor (TNFi) in quality of life (Qol), disease activity and depict possible baseline predictors for gains in Qol. METHODS: Patients followed prospectively by the Hellenic Registry of Biologic Therapies were analysed. Demographics were recorded at baseline, while RA-related characteristics at baseline and every 6 months. Paired t-tests were used to detect divergences between patient-reported (Health Assessment Questionnaire (HAQ), EuroQol (EQ-5D)) and clinical tools (Disease Activity Score-28 joints (DAS28)). Clinical versus self-reported outcomes were examined via cross-tabulation analysis. Multiple regression analysis was performed for identifying baseline predictors of improvements in QALYs. RESULTS: We analysed 255 patients (age (mean±SD) 57.1±13.0, disease duration 9.2±9.1 years, prior non-biologic disease-modifying anti-rheumatic drugs 2.3±1.2). Baseline EQ-5D, HAQ and DAS28 were 0.36 (0.28), 1.01 (0.72) and 5.9 (1.3), respectively, and were all significantly improved after 12 months (0.77 (0.35), 0.50 (0.66), 3.9 (1.5), respectively, p<0.05 for all). 90% of patients who improved from high to a lower DAS28 status (low-remission or moderate) had clinically important improvement in Qol (phi-coefficient=0.531,p<0.05). Independent predictors of gains in Qol were lower baseline HAQ, VAS global and younger age (adjusted R2=0.27). CONCLUSIONS: In daily practice TNFi improve both disease activity and Qol for the first 12 months of therapy. 90% of patients who improved from high to a lower DAS28 status had clinically important improvement in Qol. Younger patients starting with lower HAQ and VAS global are more likely to benefit.
27736998 Evaluation of Audiometric Test Results to Determine Hearing Impairment in Patients with Rh 2016 This study aimed to evaluate the association between rheumatoid arthritis (RA) and hearing impairment in the Korean adult population. Audiometric and laboratory test data from the 2010-2012 Korean National Health and Nutrition Examination Survey (KNHANES) were used for analysis. The relationship between RA and hearing impairment was analyzed, adjusting for various known risk factors associated with hearing impairment. RA was defined in the questionnaire as "RA diagnosed by a physician (yes/no) through a standardized interview." We defined hearing impairment according to 2 categories of frequency (low/mid and high) as follows (average values in kHz): low/mid frequency, 0.5, 1.0, and 2.0, and high frequency, 3.0, 4.0, and 6.0. Of the subjects, 15,158 (weighted n = 32,035,996) completed the audiometric tests. The overall weighted prevalence of RA was 1.5%. The prevalence of hearing impairment was higher in the subjects with RA than in those without RA, in both, the low/mid- and high-frequency categories (21.1% vs 7.5%, p < 0.001 and 43.3% vs. 26.2%, p < 0.001, respectively). In the multivariable logistic analysis, RA (odds ratios [OR] 1.47, 95% confidence interval [CI] 1.05-2.06, p = 0.025) was an independent risk factor of low/mid-frequency hearing impairment along with age (OR 1.12, 95% CI 1.12-1.13, p < 0.001), current smoking (OR 1.27, 95% CI 1.03-1.56, p = 0.026), and college graduation (OR 0.53, 95% CI 0.39-0.72, p < 0.001). In the multivariable analysis of high-frequency hearing impairment, RA did not show any association with hearing impairment. This study suggests that RA is associated with low/mid-frequency hearing impairment after adjustment for various known risk factors. Further study is needed to verify the hearing impairment in RA.
27311446 Cementless total hip arthroplasty for patients with rheumatoid arthritis: a more than 10-y 2016 Aug BACKGROUND/PURPOSE: In this study, cementless THA was performed for RA patients, and its clinical outcomes, as well as radiographic findings and implant survival rates, were examined more than 10 years after surgery in comparison with the outcomes of the same procedure performed for patients with hip osteoarthritis (OA) during the same period. METHOD: We studied 28 cases of THA for RA clinically and radiologically at a minimum follow-up duration of 10 years. The patients consisted of 4 males and 22 females, with a mean age at the time of surgery of 53.1. The clinical and radiographic results were compared with an age-matched and sex-matched group of patients who had undergone THA for the diagnosis of primary or secondary OA. RESULTS: In the RA group, the mean Harris hip score was 48.3 before surgery, and improved to 76.8 at the time of the final survey. In the control group, the score also improved from 46.8 before to 86.5 after surgery, while revealing significant differences between the groups (p = 0.0002). In the RA group, 2 joints required revision THA on the acetabular side due to aseptic loosening, while such revision was not performed on the femoral side despite the presence of more than 2 mm of subsidence in 2 joints. The implant survival rate was 92.9 and 100 % in the RA and control groups, respectively, without significant differences (p = 0.493). CONCLUSIONS: Although its clinical outcomes were significantly different from those for OA, a satisfactory implant survival rate was achieved, at 92.9 % in RA patients.
26616293 Increased expression of long noncoding RNAs LOC100652951 and LOC100506036 in T cells from 2016 Apr The aim of this study was to evaluate whether the presence of aberrantly expressed lncRNAs could promote T cell inflammatory responses in patients with RA. The expression levels of 10 potential aberrantly expressed lncRNAs were evaluated in T cells from 39 patients with RA and 17 controls using real-time reverse transcription polymerase chain reaction. The aberrantly expressed lncRNAs were measured in Jurkat cells co-cultured with or without ionomycin and phorbol 12-myristate 13-acetate. Transfection studies using small interfering RNA (siRNA) were conducted for biological functions, and microarray analysis was performed to search for target genes of specific lncRNAs. We confirmed that the expression levels of LOC100652951 and LOC100506036 were higher in RA T cells compared with controls. RA patients treated with biologic agents had lower expression levels of LOC100652951, and female RA patients had lower LOC100506036 expression levels after multivariate analysis. After activation, the expression levels of LOC100506036, but not LOC100652951, increased in Jurkat cells. Transfection of siRNA targeting LOC100506036 inhibited interferon gamma production and the expression of nuclear factor of activated T cells in activated Jurkat cells. After the microarray analysis with validation, inhibition of LOC100506036 expression by siRNA leaded to the decreased expression of sphingomyelin phosphodiesterase 1 (SMPD1). In conclusion, the expression levels of LOC100652951 and LOC100506036 were increased in RA T cells. Treatment with biologic agents could lower the expression of LOC100652951 in RA T cells. LOC100506036 could regulate the expression of SMPD1 and NFAT1 and could contribute to the inflammatory responses in RA.
27071670 Inflammatory properties of inhibitor of DNA binding 1 secreted by synovial fibroblasts in 2016 Apr 12 BACKGROUND: Inhibitor of DNA binding 1 (Id1) is a nuclear protein containing a basic helix-loop-helix (bHLH) domain that regulates cell growth by selective binding and prevention of gene transcription. Sources of Id1 production in rheumatoid arthritis synovial tissue (RA ST) and its range of functional effects in RA remain to be clarified. METHODS: We analyzed Id1 produced from synovial fibroblasts and endothelial cells (ECs) with histology and real-time polymerase chain reaction (RT-PCR). Fibroblast supernatants subjected to differential centrifugation to isolate and purify exosomes were measured for Id1 by enzyme-linked immunosorbent assay (ELISA). Western blotting of Id1-stimulated ECs was performed to determine the kinetics of intracellular protein phosphorylation. EC intracellular signaling pathways induced by Id1 were subsequently targeted with silencing RNA (siRNA) for angiogenesis inhibition. RESULTS: By PCR and histologic analysis, we found that the primary source of Id1 in STs is from activated fibroblasts that correlate with inflammatory scores in human RA ST and in joints from K/BxN serum-induced mice. Normal (NL) and RA synovial fibroblasts increase Id1 production with stimulation by transforming growth factor beta (TGF-β). Most of the Id1 released by RA synovial fibroblasts is contained within exosomes. Endothelial progenitor cells (EPCs) and human dermal microvascular ECs (HMVECs) activate the Jnk signaling pathway in response to Id1, and Jnk siRNA reverses Id1-induced HMVEC vessel formation in Matrigel plugs in vivo. CONCLUSIONS: Id1 is a pleotropic molecule affecting angiogenesis, vasculogenesis, and fibrosis. Our data shows that Id1 is not only an important nuclear protein, but also can be released from fibroblasts via exosomes. The ability of extracellular Id1 to activate signaling pathways expands the role of Id1 in the orchestration of tissue inflammation.
26472414 The Risk of Tuberculosis in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis 2015 Dec OBJECTIVE: Tumor necrosis factor-α (TNF-α) antagonists have significantly improved treatment results in rheumatoid arthritis (RA), but have also increased the risk of tuberculosis (TB). Etanercept (ETN), adalimumab (ADA), infliximab (IFX), golimumab, and certolizumab pegol are the 5 drugs currently available on the market. This article aimed to evaluate the risk of TB infection from these 5 drugs for patients with RA. METHODS: We searched PubMed, EMBASE, COCHRANE library, OVID, and EBSCO for randomized controlled trials (RCT) of TNF-α antagonist versus control and registry/longitudinal cohort studies of 1 TNF-α antagonist versus another. The Mantel-Haenszel test was adopted to analyze risk ratio (RR) in this metaanalysis. RESULTS: Fifty RCT and 13 non-RCT were included in this study. No significant difference in TB risk was found in the RCT because of the short observational periods. In the non-RCT, TNF-α antagonist was associated with a higher TB risk in patients with RA (RR 4.03, 95% CI 2.36-6.88), and the TB incidence rates of IFX and ADA were 2.78 and 3.88 times, respectively, higher than that of ETN. Further, preventive treatment for latent TB infection (LTBI) was shown to reduce the TB risk by 65% (RR 0.35, 95% CI 0.15-0.82). CONCLUSION: This study demonstrated a significant increase in TB risk in patients with RA treated with TNF-α antagonists; among them, ETN is least likely to cause active TB. The study also proposes the necessity of LTBI prophylaxis in patients with RA.
25731768 Rheumatoid arthritis and the prevalence of diabetic retinopathy. 2015 Aug OBJECTIVE: RA increases vascular disease and angiogenesis, yet a 1964 Lancet report paradoxically linked RA to lower diabetic retinopathy. Our objective was to examine RA as a risk factor for diabetic retinopathy compared with other vascular risk factors. METHODS: This cohort study compared the prevalence of diabetic retinopathy in diabetes patients with and without RA in a 5% Medicare sample. We analysed the impact of RA on the prevalence of diabetic retinopathy using multivariate logistic regression calculating adjusted rate ratios (ARRs) controlling for sociodemographics, co-morbidity and health utilization. Sensitivity analysis examined eye exam rates. RESULTS: Among 256 331 Medicare diabetes patients, 5572 (2%) had RA. Diabetic retinopathy was less prevalent in patients with RA compared with those without RA (13.7% vs 16.1%, P ≤ 0.01). Compared with patients without RA, the adjusted model demonstrated that patients with diabetes and RA were 28% less likely to have diabetic retinopathy and 4% more likely to receive an eye exam [ARR 0.72 (95% CI 0.67, 0.77), ARR 1.04 (95% CI 1.02, 1.06)]. CONCLUSION: Findings support the 1964 paradox observing decreased diabetic retinopathy in patients with RA. These findings pose new questions regarding whether RA physiology or treatments protect against diabetic retinopathy and how intraocular factors vary in contrast to adverse vascular changes elsewhere.
27858176 Serum level of reactive oxygen metabolites (ROM) at 12 weeks of treatment with biologic a 2017 Feb We have shown that serum levels of reactive oxygen metabolites (ROM) were associated with C-reactive protein (CRP) and disease activity score based on the examination of 28 joints (DAS28) in patients with rheumatoid arthritis (RA); however, their clinical significance as biomarkers has not been elucidated. Forty-eight biologic agent (BA)-naïve RA patients were included in this study. Associations between serum levels of ROM, CRP, matrix metalloproteinase-3 (MMP-3), DAS28-erythrocyte sedimentation rate (ESR), and Health Assessment Questionnaire (HAQ) at 12 weeks of treatment and DAS28 (ESR) remission at 52 weeks (52-week remission) were investigated. The ROM serum level at baseline in the remission group (n = 34) was 527 ± 132 Carratelli units (U.Carr) (normal range <300), decreased to 335 ± 79.1 at 4 weeks, and remained low thereafter. In the non-remission group (n = 14), the ROM serum level at baseline was 592 ± 113 U.Carr, decreased to 450 ± 152 at 4 weeks, but gradually increased thereafter. Among significantly different factors at 12 weeks between the remission and non-remission groups, ROM and DAS28 (ESR) were identified as predictors of 52-week remission (p = 0.045, odds ratio 0.985, 95% confidence interval 0.97-1.000 for ROM). The cutoff value of ROM was determined to be 381.5 U.Carr (sensitivity 0.833, specificity 0.871). These results show that serum ROM levels can predict remission with high accuracy and could be a useful biomarker for achieving remission in the current treat-to-target strategy for RA.
26034147 Treatment Patterns of Multimorbid Patients with Rheumatoid Arthritis: Results from an Inte 2015 Jul OBJECTIVE: To describe the treatment profile of multimorbid patients with rheumatoid arthritis (RA) in contrast to patients with RA only. METHODS: COMORA (Comorbidities in Rheumatoid Arthritis) is a cross-sectional, international study assessing morbidities, outcomes, and treatment of patients with RA. Patients were grouped according to their multimorbidity profile assessed by a counted multimorbidity index (cMMI). Treatment for RA was categorized as use of biologic disease-modifying antirheumatic drugs (bDMARD), in particular tumor necrosis factor inhibitors (TNFi), synthetic DMARD (sDMARD) use only, nonsteroidal antiinflammatory drug (NSAID) use, and corticosteroid use. Logistic regression models were performed to determine the OR of bDMARD, TNFi, sDMARD, NSAID, or corticosteroid use based on a patient's cMMI and global region after adjusting for age, disease activity, disease duration, educational level, and previous DMARD therapy. RESULTS: Out of 3920 patients, 32.7% received bDMARD; 59.9% sDMARD only, 51.1% used concomitant NSAID, and 54.8% used corticosteroid. Regional differences were observed with the most frequent use of bDMARD in the United States (46.5%) and lowest in North Africa (9%). After adjusting for confounders in logistic regression, the OR for bDMARD use was reduced for each additional morbidity (OR 0.89, 95% CI 0.83-0.96). Similar results were found for TNFi (OR 0.91, 95% CI 0.84-0.99), whereas the OR for use of sDMARD was increased (1.13, 95% CI 1.05-1.22). No significant change of OR was found for NSAID or corticosteroid use. CONCLUSION: In this study, the odds of bDMARD use decreases 11% for each additional chronic morbid condition after adjustment for regional differences, disease activity, and other covariates.
26896473 Tetrahydrobiopterin Supplementation Improves Endothelial Function But Does Not Alter Aorti 2016 Feb 19 BACKGROUND: Rheumatoid arthritis is a systemic inflammatory condition associated with increased cardiovascular risk that may be due to underlying endothelial dysfunction and subsequent aortic stiffening. We hypothesized that supplementation with tetrahydrobiopterin (BH4) would recouple endothelial nitric oxide synthase and thus improve endothelial function and consequently reduce aortic stiffness. METHODS AND RESULTS: We conducted 2 randomized, double-blinded, placebo-controlled crossover studies examining 2 separate regimens: an acute regimen, with a single dose of BH4 400 mg versus placebo (n=18), and a short-term regimen, composed of a 1-week treatment with BH4 400 mg once daily versus placebo (n=15). Flow-mediated dilatation and aortic pulse wave velocity were studied 4 times, before and after each treatment phase. Acute BH4 supplementation led to an improvement of flow-mediated dilatation, whereas placebo had no effect (mean±SD of effect difference 2.56±4.79%; P=0.03). Similarly, 1-week treatment with BH4 improved endothelial function, but there was no change with placebo (mean±SD of effect difference 3.50±5.05%; P=0.02). There was no change in aortic pulse wave velocity following acute or short-term BH4 supplementation or placebo (mean±SD of effect difference: acute 0.09±0.67 m/s, P=0.6; short-term 0.03±1.46 m/s, P=0.9). CONCLUSION: Both acute and short-term supplementation with oral BH4 improved endothelial function but not aortic stiffness. This result suggests that BH4 supplementation may be beneficial for patients with rheumatoid arthritis by improving endothelial dysfunction and potentially reducing risk of cardiovascular disease. There appears to be no causal relationship between endothelial function and aortic stiffness, suggesting that they occur in parallel, although they may share common risk factors such as inflammation.
27233001 The association between reduced folate carrier-1 gene 80G/A polymorphism and methotrexate 2016 Sep Methotrexate (MTX), the most commonly used anti-rheumatic drug against RA, enters the cell via the action of the reduced folate carrier 1(RFC1). A major polymorphism of the RFC1 gene, 80G/A, has been reported to influence the activity of RFC1, resulting in variable intracellular MTX-polyglutamate (MTX-PG) levels. However, the association studies addressing the RFC1 80G/A polymorphism and MTX efficacy or toxicity in Rheumatoid arthritis (RA) has yielded conflicting results. In the present meta-analysis, we aimed to evaluate the association between the RFC1 80G/A polymorphism and MTX efficacy or toxicity in RA patients. A total 17 studies met our inclusion criteria. Among them, 12 studies with 2049 subjects reported the association between the RFC1 80G/A and MTX response, and 12 studies involving 2627 subjects were on MTX-related toxicity. Meta-analysis revealed significant association between RFC1 80G/A polymorphism and MTX efficacy (odds ratio (OR) for the A allele=1.29, 95% confidence interval (CI) 1.05-1.67, P=0.02; for AA genotype: OR=1.49, 95%CI 1.17-1.907, P=0.001). However, no association could be detected in the analysis of MTX-related toxicity. Stratification by ethnic population also indicated an association between this polymorphism and MTX efficacy in Asian group (P=0.002 for A allele; P=0.003 for AA genotype), but not in the Caucasian group (P=0.15 for A allele; P=0.05 for AA genotype). In both Asian and Caucasian sub-groups, no influence of the RFC1 80G/A polymorphism on MTX toxicity can be detected. In conclusion, the RFC1 G80A polymorphism is associated with responsiveness to MTX therapy, but may not be associated with MTX toxicity in RA patients.
25777147 Can the ankle brachial pressure index (ABPI) and carotis intima media thickness (CIMT) be 2015 Jul BACKGROUND: It takes years for atherosclerosis to manifest symptoms. However, it needs to be identified earlier because of the premature cardiovascular risk factors in patients with rheumatoid arthritis (RA). In this study, we aimed to investigate the effect of atherosclerosis on the ankle brachial pressure index (ABPI) and carotis intima media thickness (CIMT) in patients with RA. METHODS: RA patients attending the rheumatology clinic were examined retrospectively; then we called them for the measurements of ABPI and CIMT prospectively. Subjects were divided into four groups, as follows (Table 1): group 1 comprised RA patients with an ABPI less than 0.9; group 2 included RA patients with an ABPI between 0.9 and 1.2; group 3 was made up of RA patients with an ABPI greater than 1.2; and group 4 included patients without RA with an ABPI between 0.9 and 1.2 as a control group. Patients' demographic data were recorded. Hypertension (HT), diabetes mellitus, ABPI and CIMT measurements were taken by specialists. Duration of RA and disease scores (disease activity score-28, health assessment questionnaire score and visual assessment score) were recorded. RESULTS: The prevalence of peripheral vascular disease in patients with RA was twice as high as that in the normal population of equivalent age. Patients in group 2, with RA and normal ABPI, exhibited a significant higher mean in CIMT (mm) compared with the control group (p < 0.01), despite having normal ABPI. This confirms that these patients have a higher risk of stroke compared with the control group. Group 1's newly diagnosed HT (p < 0.01) and systolic blood pressure (SBP) values (p < 0.01) were higher and statistically significant when compared with the group 4 (control group); in addition, significant plaque levels were observed in the carotid arteries (p < 0.01). Group 3 patients had a similar history of HT and increased SBP compared with patients in group 4 (p < 0.01), and had similar characteristics to with group 1. No statistically significant differences were found between the groups in terms of inflammatory markers such as C-reactive protein and rheumatoid factor, anti-cyclic citrullinated peptide and white blood cell counts. CONCLUSION: Based on the present findings, patients with RA need to be evaluated in the early stage of the disease for subclinical peripheral artery disease using the ABPI, as well as CIMT, which is also a non-invasive technique, in terms of cerebrovascular events. Inflammatory markers exhibited no statistically significant difference. We think that the atherosclerotic process stems not only from the inflammatory effects of RA, but also perhaps from its immunological nature.
26097225 Use of ultrasound-guided small joint biopsy to evaluate the histopathologic response to rh 2015 Oct OBJECTIVE: To examine in a cohort of rheumatoid arthritis (RA) patients undergoing serial ultrasound (US)-guided biopsies of small joints in the context of clinical trials whether sufficient synovial tissue could be obtained at both baseline and second biopsy to: 1) accurately evaluate the synovial immune phenotype, 2) permit adequate RNA extraction to determine molecular signatures, and 3) sensitively detect change in the number of synovial sublining macrophages (CD68+) following effective therapy. METHODS: Synovial samples from RA patients undergoing US-guided biopsy of small joints as part of 2 clinical trials (Barts Early Arthritis Cohort [n = 18] and the Clinical and Pathological Response to Certolizumab Pegol (CLIP-Cert) study [n = 17]) were examined, and the quality and quantity of histologic samples and RNA extracted per joint were determined and compared to synovial thickness and power Doppler scores determined by US before biopsy. Modulation of the number of CD68+ sublining macrophages was correlated with clinical response to treatment. RESULTS: Good quality synovial tissue that accurately reflected the synovial immune phenotype of the total joint was obtained in 80% of US-guided procedures when synovial thickness (higher than grade 2) was documented before biopsy. In 100% of the procedures, sufficient RNA was extracted to permit molecular analysis. There was a significant correlation between change in CD68+ sublining macrophage number and clinical response to treatment. CONCLUSION: This study provides minimum standards for sample retrieval for small joint biopsy. Furthermore, our findings confirm the clinical utility of the procedure in the largest reported cohort of US-guided small joint biopsies. The demonstration that small joint synovial tissue can be readily accessed by a technically simple, minimally invasive procedure is likely to facilitate critical advancements in the knowledge of RA pathobiology and personalized health care.