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ID PMID Title PublicationDate abstract
27926504 The immunomodulatory effects of TNF-α inhibitors on human Th17 cells via RORγt histone a 2017 Jan 31 The presence of interleukin (IL)-17-related cytokines correlates with rheumatoid arthritis (RA) pathogenesis. Epigenetic modifications, including histone acetylation, regulate gene expression in RA pathogenesis. Tumour necrosis factor-alpha (TNF-α) inhibitors such as etanercept and adalimumab, represent a breakthrough in RA treatment. We aimed to investigate the effects of etanercept and adalimumab on human Th17-polarized cells and the possible intracellular regulators of these effects, including the Th17-specific transcription factors signal transducer, activator of transcription 3 (STAT3), retinoid-related orphan receptor γ-T (RORγt) and epigenetic modification. Human CD4+ T cells from healthy subjects and patients with RA were pretreated with TNF-α inhibitors and then being polarized into IL-17-producing cells. The Th17-related cytokine levels in the culture supernatants were determined with an enzyme-linked immunosorbent assay. Intracellular signalling was investigated by western blot, real-time RT-PCR, and chromatin immunoprecipitation. Th17-polarized cells from patients with RA produced more IL-17A, IL-17F and IL-22 than those from healthy subjects. Etanercept and adalimumab suppressed IL-17A, IL-17F and IL-22 levels in Th17-polarized cells from healthy subjects and patients with RA. Western blot analysis revealed that etanercept and adalimumab decreased mitogen-activated protein kinase-phospho-p38, nuclear factor-κB-phospho-p65, phospho-STAT3 and RORγt levels. Etanercept and adalimumab decreased histone (H)3 and H4 acetylation in the RORγt gene promotor region by decreasing the recruitment of the acetyltransferases p300, CBP and PCAF. The present study broadens our knowledge of the mechanisms underlying the immunomodulatory effects of TNF-α inhibitors in rheumatoid arthritis treatment.
28216195 Golimumab in real-life settings: 2 Years drug survival and predictors of clinical outcomes 2017 Aug OBJECTIVES: To assess the drug survival of golimumab, and predictors thereof, in patients affected with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) in a prospective observational cohort. METHODS: This is a non-interventional, longitudinal study on RA, SpA, and PsA patients starting treatment with golimumab. Endpoints were the 2 years persistence rate of golimumab and predictors of therapy discontinuation. Drug retention was analyzed using Kaplan-Meier and Cox models. Hazard ratios (HR) of golimumab discontinuation were estimated by Cox-regression hazard models. RESULTS: Of 416 patients starting golimumab, 171 biologic-naïve and 245 inadequate responders to prior biologic drugs, 88 had RA, 147 SpA, and 181 PsA. Global 2 years drug retention was 70.2%, with no different hazard of discontinuation among diseases or line of biologic treatment. The strongest predictor of golimumab discontinuation was female gender (HR = 1.95). Golimumab monotherapy was associated with higher risk drug interruption (HR = 1.67). Within SpA, predictors of golimumab discontinuation were female sex (HR = 4.19), and absence of extra-articular manifestations (HR = 4.60). In PsA, duration of disease was negatively associated to drug interruption (HR = 0.93), whereas golimumab monotherapy was positively (HR = 2.21) associated. Interestingly, failing to achieve a good EULAR response at 3 months was the only predictor of golimumab discontinuation for RA patients (HR = 3.03). CONCLUSIONS: This study provided evidence that golimumab has high retention rate in real-life settings. SpA male patients with extra-articular manifestations, PsA patients on co-therapy with DMARDs, and RA patients attaining an early clinical response had the highest probability to continue golimumab over 2 years.
28948174 Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Patho 2017 Characterization and understanding of gut microbiota has recently increased representing a wide research field, especially in autoimmune diseases. Gut microbiota is the major source of microbes which might exert beneficial as well as pathogenic effects on human health. Intestinal microbiome's role as mediator of inflammation has only recently emerged. Microbiota has been observed to differ in subjects with early rheumatoid arthritis compared to controls, and this finding has commanded this study as a possible autoimmune process. Studies with intestinal microbiota have shown that rheumatoid arthritis is characterized by an expansion and/or decrease of bacterial groups as compared to controls. In this review, we present evidence linking intestinal dysbiosis with the autoimmune mechanisms involved in the development of rheumatoid arthritis.
28150777 Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthr 2017 Feb 1 CD4(+) T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4(+) T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1(hi)CXCR5(-)CD4(+) T cells in synovium of patients with rheumatoid arthritis. However, these cells are not exhausted, despite high PD-1 expression. Rather, using multidimensional cytometry, transcriptomics, and functional assays, we define a population of PD-1(hi)CXCR5(-) 'peripheral helper' T (T(PH)) cells that express factors enabling B-cell help, including IL-21, CXCL13, ICOS, and MAF. Like PD-1(hi)CXCR5(+) T follicular helper cells, T(PH) cells induce plasma cell differentiation in vitro through IL-21 secretion and SLAMF5 interaction (refs 3, 4). However, global transcriptomics highlight differences between T(PH) cells and T follicular helper cells, including altered expression of BCL6 and BLIMP1 and unique expression of chemokine receptors that direct migration to inflamed sites, such as CCR2, CX3CR1, and CCR5, in T(PH) cells. T(PH) cells appear to be uniquely poised to promote B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues.
27860410 Sarilumab and Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rh 2017 Feb OBJECTIVE: To evaluate the efficacy and safety of sarilumab plus conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with active moderate-to-severe rheumatoid arthritis (RA) who had an inadequate response or intolerance to anti-tumor necrosis factor (anti-TNF) therapy. METHODS: Patients were randomly allocated to receive sarilumab 150 mg, sarilumab 200 mg, or placebo every 2 weeks for 24 weeks with background conventional synthetic DMARDs. The co-primary end points were the proportion of patients achieving a response according to the American College of Rheumatology 20% criteria for improvement (ACR20) at week 24, and change from baseline in the Health Assessment Questionnaire disability index (HAQ DI) at week 12. Each sarilumab dose was evaluated against placebo; differences between the 2 sarilumab doses were not assessed. RESULTS: The baseline characteristics of the treatment groups were similar. The ACR20 response rate at week 24 was significantly higher with sarilumab 150 mg and sarilumab 200 mg every 2 weeks compared with placebo (55.8%, 60.9%, and 33.7%, respectively; P < 0.0001). The mean change from baseline in the HAQ DI score at week 12 was significantly greater for sarilumab (least squares mean change: for 150 mg, -0.46 [P = 0.0007]; for 200 mg, -0.47 [P = 0.0004]) versus placebo (-0.26). Infections were the most frequently reported treatment-emergent adverse events. Serious infections occurred in 1.1%, 0.6%, and 1.1% of patients receiving placebo, sarilumab 150 mg, and sarilumab 200 mg, respectively. Laboratory abnormalities included decreased absolute neutrophil count and increased transaminase levels in both sarilumab groups compared with placebo. In this study, reductions in the absolute neutrophil count were not associated with an increased incidence of infections or serious infections. CONCLUSION: Sarilumab 150 mg and sarilumab 200 mg every 2 weeks plus conventional synthetic DMARDs improved the signs and symptoms of RA and physical function in patients with an inadequate response or intolerance to anti-TNF agents. Safety data were consistent with interleukin-6 receptor blockade and the known safety profile of sarilumab.
28193225 The active metabolite of leflunomide, A77 1726, attenuates inflammatory arthritis in mice 2017 Feb 13 BACKGROUND: Leflunomide is a low-molecular-weight compound that is widely used in the treatment of rheumatoid arthritis. Although leflunomide is thought to act through the inhibition of the de novo pyrimidine synthesis, the molecular mechanism of the drug remains largely unknown. We investigated the antiarthritis effects and mechanisms of action of the active metabolite of leflunomide, A77 1726, in interleukin-1 receptor antagonist-knockout (IL-1Ra-KO) mice. METHODS: 14- to 15-week-old male IL-1Ra-KO mice were treated with 10 or 30 mg/kg A77 1726 via intraperitoneal injection three times per week for 6 weeks. The effects of A77 1726 on arthritis severities were assessed by clinical scoring and histological analysis. The serum concentrations of IL-1β, tumor necrosis factor-α (TNF-α), and malondialdehyde were measured by enzyme-linked immunosorbent assay. Histologic analysis of the joints was performed using Safranin O, and immunohistochemical staining. The frequencies of interleukin-17-producing CD4(+) T (Th17) cells were analyzed by flow cytometry. Heme oxygenase-1 (HO-1) expression in splenic CD4(+) T cells isolated from A77 1726-treated arthritis mice were assessed by western blotting. RESULTS: A77 1726 treatment induced heme oxygenase-1 (HO-1) in Jurkat cells and primary mouse T cells. Interestingly, A77 1726 inhibited Th17 cell differentiation. In vivo, A77 1726 reduced the clinical arthritis severity of histological inflammation and cartilage destruction. The joints isolated from A77 1726-treated mice showed decreased expression of inducible nitric oxide synthase, nitrotyrosine, TNF-α, and IL-1β. The serum levels of TNF-α, IL-1β, and malondialdehyde were also decreased in A77 1726-treated mice. Whereas the number of Th17 cells in spleens was decreased in A77 1726-treated arthritis mice, a significant increase in the number of Treg cells in spleens was observed. Interestingly, HO-1 expression was significantly higher in splenic CD4(+) T cells isolated from A77 1726-treated mice compared with those from vehicle-treated mice, whereas HO-1 expression of splenic non-CD4(+) T cells did not differ between groups. CONCLUSION: The inhibitory effects of A77 1726 on joint inflammation and oxidative stress in autoimmune arthritis may be associated with HO-1 induction in CD4(+) T cells.
28598774 What could we learn from the sub-analysis of a single nation cohort in a worldwide study? 2017 Jul OBJECTIVES: GO-MORE Trial investigated the use of Golimumab (GLM) in 3280 rheumatoid arthritis (RA) patients worldwide. At present, the burden of arthritis is greater in poorer countries than in developed countries due to socioeconomic disparities, thus suggesting the usefulness of subgroup investigations. We aimed to evaluate GLM as add-on therapy for RA patients in the Italian cohort of GO-MORE trial and compared the clinical characteristics between Italian patients and the enrolled patients worldwide. METHODS: Ninety-eight Italian patients with active RA, fulfilling the 1987 ACR criteria were enrolled. Statistical analyses were performed to assess: i. the differences in baseline characteristics; ii. the efficacy after 6 months; between Italian and Rest of the World GO-MORE populations. RESULTS: Compared to the worldwide population, Italian patients showed a lower value of disease activity and a significantly short disease duration. Unlike the worldwide patients, the large majority of Italian patients received biologic therapy after the failure of the first synthetic DMARD and were not treated by high methotrexate dosage. After 6 months of GLM treatment, no differences were observed in the therapeutic response. Italian patients reported a positive autoinjection experience mirroring the worldwide results. CONCLUSIONS: The analysis of the Italian GO-MORE subset confirms that differences among patients may be shown, depending on different approaches in different health systems. GLM in the Italian patients showed a favourable benefit/risk profile and the positive autoinjection experience may help with patient's compliance and survival of the treatment.
28687489 Fas/S1P(1) crosstalk via NF-κB activation in osteoclasts controls subchondral bone remode 2017 Sep 2 Enhanced turnover of subchondral trabecular bone is a hallmark of rheumatoid arthritis (RA) and it results from an imbalance between bone resorption and bone formation activities. To investigate the formation and activation of osteoclasts which mediate bone resorption, a Fas-deficient MRL/lpr mouse model which spontaneously develops autoimmune arthritis and exhibits decreased bone mass was studied. Various assays were performed on subchondral trabecular bone of the temporomandibular joint (TMJ) from MRL/lpr mice and MRL+/+ mice. Initially, greater osteoclast production was observed in vitro from bone marrow macrophages obtained from MRL/lpr mice due to enhanced phosphorylation of NF-κB, as well as Akt and MAPK, to receptor activator of nuclear factor-κB ligand (RANKL). Expression of sphingosine 1-phosphate receptor 1 (S1P(1)) was also significantly upregulated in the condylar cartilage. S1P(1) was found to be required for S1P-induced migration of osteoclast precursor cells and downstream signaling via Rac1. When SN50, a synthetic NF-κB-inhibitory peptide, was applied to the MRL/lpr mice, subchondral trabecular bone loss was reduced and both production of osteoclastogenesis markers and sphingosine kinase (Sphk) 1/S1P(1) signaling were reduced. Thus, the present results suggest that Fas/S1P(1) signaling via activation of NF-κB in osteoclast precursor cells is a key factor in the pathogenesis of RA in the TMJ.
27596742 Methotrexate intolerance in the treatment of rheumatoid arthritis (RA): effect of adding c 2017 Feb The aim of this study was to investigate the effect of caffeine on the symptoms of methotrexate (MTX) intolerance in patients with RA. The follow-up patients with RA seen over a period of 11 months were included in this work. The degree of MTX intolerance, if present, was classified as 'moderate' and 'severe'. Those with intolerance were advised caffeine (coffee or dark chocolate) synchronised with the MTX dose. The effect was assessed as 'very good', 'good' or 'none'. Among 855 patients seen during this period, 313 (36.6 %) did not have any MTX intolerance, 542 (63.4 %) patients had some degree of MTX intolerance, 422 (77.8 %; 49.3 % of the total patients) had 'minimal' intolerance not requiring any intervention. The remaining 120 (22.1 %) of the 542 (14 % of the total 855) patients had 'moderate' or 'severe' MTX intolerance. Among these, 55 % had complete relief of symptoms and were able to continue taking the advised dose of MTX; 13.3 % had partial improvement and continued taking MTX but only with antiemetics; 7.5 % were minimally better but were somehow managing; 10 % were complete caffeine failure without any relief; 14.2 % did not like caffeine (coffee or dark chocolate) and did not want to take it. Caffeine relieved the symptoms of MTX intolerance in 55 % and partial relief in 13 % of the patients. A significant number of patients did not like to take caffeine (coffee or dark chocolate). It is of note that northern part of India is primarily a tea-drinking population where coffee is not a favourite drink.
28836747 Clinical use of ZRC3197 (Adalimumab Biosimilar) in Patients with Inflammatory Arthritis: A 2017 May We present our real-life clinical experience of ZRC3197 (Adalimumab Biosimilar) in Indian patients with inflammatory arthritis [spondyloarthropathy (SPA) and rheumatoid arthritis (RA)]. Medical records of these patients were retrospectively retrieved and analysed at our single centre. All the patients had received biosimilar Adalimumab 40 mg every 15 days for initial 3 months. Post 3 months, an 'on-demand modified dosing approach' was followed, wherein BASDAI/DAS28-guided dose reduction or discontinuation of treatment was done. Dose reduction was primarily done by increasing the dosing interval for biosimilar Adalimumab. The 3, 6 and 12 months' follow-up data revealed a significant reduction in disease activity scores (BASDAI/DAS28). At 3 months, BASDAI50% was achieved in 91% and BASDAI 70% was achieved in 45% of SPA patients. At 3 months, 88% showed a reduction in DAS28 > 1.2 from baseline. At 12 months, 94% of the evaluable SPA patients and 58% of evaluable RA patients showed clinical remission or low disease activity. BASDAI/DAS28 score-guided dose reduction led to significantly lesser requirement of biosimilar Adalimumab doses. Biosimilar Adalimumab was well-tolerated with no serious or unexpected side effects. Our analysis suggests that disease activity-guided modified dosing may serve as an effective strategy for patients with inflammatory arthritis, leading to a lower dose requirement for the treatment. Despite the modified dosing, the clinical response following biosimilar Adalimumab was comparable to the published data for the standard Adalimumab treatment in such patients.
27755123 Anticitrullinated protein antibodies: origin and role in the pathogenesis of rheumatoid ar 2017 Jan PURPOSE OF REVIEW: This article reviews recent literature on the origin and pathogenic role of anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA). RECENT FINDINGS: ACPAs and ACPA-immune complexes interact with immune cells to facilitate articular inflammation. Findings from recent in vitro and in vivo studies are congruent with epidemiologic observations in RA supporting a pathogenic role of ACPAs. SUMMARY: ACPAs target proteins/peptides with citrullinated epitopes and serve as informative RA biomarkers. ACPAs are generated within synovium and possibly at extra-articular sites prior to disease onset. Proximate to RA onset, critical qualitative and quantitative changes to ACPAs occur that drive proinflammatory responses. Unable to induce arthritis alone, the administration of ACPAs enhances the development and severity of inflammation in mice when a mild synovitis is already present. In vitro studies have elucidated several possible mechanisms linking ACPA to disease progression including: first, activation of inflammatory cells by ACPA-immune complexes; second, ACPA-mediated neutrophil cell death producing neutrophil extracellular traps, which drives inflammation and autoimmunity by releasing citrullinated autoantigen; and finally, direct binding of ACPAs to osteoclasts and resulting osteoclastogenesis. Together, these recent investigations have begun to elucidate the different mechanisms by which ACPAs may be directly pathogenic in RA.
29022053 Glycated albumin (GA) and inflammation: role of GA as a potential marker of inflammation. 2018 Jan AIMS: Abnormal levels of glycated albumin (GA) are associated with the onset of both diabetes and inflammation. Although inflammation has long been associated with diabetes, this article aims to explore the underlying mechanisms of this relationship as it pertains to the role of GA. METHODS: We have reviewed 52 research articles since the year 2000. Common search terms used were "(inflammatory mediator) and GA" or "inflammation and GA". The findings have been organized according to diabetic complications with respect to the interactions of GA and inflammatory mediators. Glycated albumin and specific inflammatory mediators have been reported to play various roles in the pathogenesis of insulin resistance, atherosclerosis, coronary artery disease, retinopathy, and nephropathy. In the case of nephropathy and recently retinopathy, there is considerable evidence for GA in concert with inflammation playing a direct role in organ pathology. There is copious literature detailing GA's involvement in stimulating inflammatory markers and certain pro-inflammatory cytokines. A recent clinical study has shown GA to be a marker for inflammation in non-diabetic rheumatoid arthritis patients with the significance of standard inflammatory markers. CONCLUSIONS: The clinical utility of GA measurement may likely reside in its versatility as both a mediator of inflammation as well as a marker to track hyperglycemia and other diabetes complications. Further understanding of the role GA plays in glycemic and inflammatory diseases could lead to its acceptance as an independent bio-inflammatory marker.
28854271 Identification of novel genetic loci for osteoporosis and/or rheumatoid arthritis using cF 2017 There are co-morbidity between osteoporosis (OP) and rheumatoid arthritis (RA). Some genetic risk factors have been identified for these two phenotypes respectively in previous research; however, they accounted for only a small portion of the underlying total genetic variances. Here, we sought to identify additional common genetic loci associated with OP and/or RA. The conditional false discovery rate (cFDR) approach allows detection of additional genetic factors (those respective ones as well as common pleiotropic ones) for the two associated phenotypes. We collected and analyzed summary statistics provided by large, multi-center GWAS studies of FNK (femoral neck) BMD (a major risk factor for osteoporosis) (n = 53,236) and RA (n = 80,799). The conditional quantile-quantile (Q-Q) plots can assess the enrichment of SNPs related to FNK BMD and RA, respectively. Furthermore, we identified shared loci between FNK BMD and RA using conjunction cFDR (ccFDR). We found strong enrichment of p-values in FNK BMD when conditional Q-Q was done on RA and vice versa. We identified 30 novel OP-RA associated pleiotropic loci that have not been reported in previous OP or RA GWAS, 18 of which located in the MHC (major histocompatibility complex) region previously reported to play an important role in immune system and bone health. We identified some specific novel polygenic factors for OP and RA respectively, and identified 30 novel OP-RA associated pleiotropic loci. These discovery findings may offer novel pathobiological insights, and suggest new targets and pathways for drug development in OP and RA patients.
28736271 B cells and their cytokine activities implications in human diseases. 2018 Jan B cells are the only cell type that can give rise to antibody-producing cells, and the only cell type whose selective depletion can, today, lead to an improvement of a wide range of immune-mediated inflammatory diseases, including disorders not primarily driven by autoantibodies. Here, I discuss this paradoxical observation, and propose that the capacity of B cells to act as cytokine-producing cells explains how they can control monocyte activity and subsequently disease pathogenesis. Together with current data on the effect of anti-CD20 B cell-depleting reagents in the clinic, this novel knowledge on B cell heterogeneity opens the way for novel safer and more efficient strategies to target B cells. The forthcoming identification of disease-relevant B cell subsets is awaited to permit their monitoring and specific targeting in a personalized medicine approach.
28302406 Docosahexaenoic acid in the treatment of rheumatoid arthritis: A double-blind, placebo-co 2018 Apr The potential of fish or fish oil as supplier for eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) for reducing cardiovascular risk factors and supporting therapy of chronic inflammatory diseases, has been investigated intensively, but our knowledge about the physiological effects of the individual compounds EPA and DHA are limited. STUDY DESIGN: In this double-blind pilot study, thirty-eight patients with defined RA were allocated to consume foods enriched with microalgae oil from Schizochytrium sp. (2.1 g DHA/d) or sunflower oil (placebo) for 10 weeks (cross-over), maintaining the regular RA medication during the study. RESULTS: In contrast to placebo, the daily consumption of DHA led to a decline in the sum of tender and swollen joints (68/66) from 13.9 ± 7.4 to 9.9 ± 7.0 (p = 0.010), total DAS28 from 4.3 ± 1.0 to 3.9 ± 1.2 (p = 0.072), and ultrasound score (US-7) from 15.1 ± 9.5 to 12.4 ± 7.0 (p = 0.160). The consumption of placebo products caused an increase of the n-6 PUFA linoleic acid and arachidonic acid (AA) in erythrocyte lipids (EL, p < 0.05). The amount of DHA was doubled in EL of DHA-supplemented patients and the ratios of AA/EPA and AA/DHA dropped significantly. We speculate that the production of pro-inflammatory/non-resolving AA-derived eicosanoids might decrease in relation to anti-inflammatory/pro-resolving DHA- and EPA-derived lipid mediators. In fact, plasma concentrations of AA-derived thromboxane B(2) and the capacity of blood to convert AA to the pro-inflammatory 5-lipoxygenase product 5-hydroxyeicosatetraenoic acid were significantly reduced, while levels of the DHA-derived maresin/resolvin precursors 14-/17-hydroxydocosahexaenoic acid significantly increased due to DHA supplementation. CONCLUSION: The study shows for the first time that supplemented microalgae DHA ameliorates disease activity in patients with RA along with a shift in the balance of AA- and DHA-derived lipid mediators towards an anti-inflammatory/pro-resolving state.
30695433 [Effects of Huatan Tongluo Recipe on IL-1β-induced Proliferation of Rheumatoid Arthritis 2017 Jan Objective To observe the effects of Huatan Tongluo Recipe (HTTLR) on the proliferation of IL-β p induced rheumatoid arthritis synovial fibroblast ( RASFB) and secretion of necrosis factor α (TNF-α) and acidic fibroblast growth factor (aFGF) in vitro. Methods RASFB cell line was cultured in vitro and stimulated by IL-1β. The proliferation of RASFB was detected using WST-1 after adding IL-1β with final concentrations of 1 , 5, 10, 20 μg/L for 24 and 48 h respectively. Then 20 μg/L IL-1β recruited as induction dose was set up as IL-1β group. High, middle, low dose HTTLR groups were set up by adding HT- TLR decoction with final concentration of 5%, 2%, 1% (V/V) , respectively for 24 and 48 h. A blank con- trol group was also set up. The proliferation rates were compared. Contents of TNF-α and aFGF were detected in each group using ELISA. mRNA expressions of TNF-α and aFGF were detected using RT-PCR. Results The proliferation rates of RASFB at 24 h and 48 h were lower at 1 μg/L IL-1 β than at 5, 10, 20 μg/L IL-1β (P <0. 01). The proliferation rate of RASFB was higher at 10 and 20 μg/L IL-1β than at 5 μg/L IL-1β (P <0. 01). Besides, the proliferation rate of RASFB was higher at 20 μg/L IL-1β than at 10 μg/L IL-1 β (P <0. 01). The proliferation rate of RASFB was higher at 48 h than at 24 h (P <0. 01). Com- pared with the high dose HTTLR group, the proliferation rate of RASFB was lowered in middle and low dose HTTLR groups (P <0. 01). Besides, IL-1β induced proliferation rate of RASFB was obviously reduced in the middle dose HTTLR group (P <0. 01). Compared with the blank control group, mRNA ex- pressions of TNF-α and aFGF and their contents were elevated in the IL-1β group at 24 and 48 h (P < 0. 05). Compared with the IL-1 β group, mRNA expressions of TNF-α- and aFGF and their contents, except TNF-α- mRNA expression in the low dose HTTLR group at 24 h, were all obviously lowered in 3 dose HTTLR groups at 24 h and 48 h (P <0. 05). Compared with the high dose HTTLR group, mRNA expressions of TNF-(α and aFGF increased in middle and low dose HTTLR groups at 24 h and 48 h; TNF-α content in the low dose HTTLR group at 24 h; contents of TNF-α and aFGF in middle and low dose HTTLR groups at 24 h and 48 h all increased (P <0. 05). Conclusion The mechanism of HTTLR treatment for RA might be related to inhibiting RASFB proliferation, and decreasing mRNA expressions of TNF-α and aFGF as well as their protein secretion.
27390167 Variations in Radiographic Procedure Use for Medicare Patients With Rheumatoid Arthritis. 2017 May OBJECTIVE: In 2013, the American College of Rheumatology published its Choosing Wisely list, which identified 2 radiographic procedures (peripheral joint magnetic resonance imaging [MRI] and dual x-ray absorptiometry [DXA] scans) that were at risk for overuse. METHODS: We performed a retrospective cross-sectional cohort study to measure the use of peripheral joint MRI, peripheral joint radiographs, and DXA scans in a national cohort of Medicare patients with rheumatoid arthritis (RA) during 2008-2009, before the start of the Choosing Wisely campaign. Diagnoses were identified via International Classification of Diseases, Ninth Revision, codes; utilization was calculated using Current Procedural Terminology codes. Utilization was analyzed at the individual level and at the regional level (by hospital referral region [HRR]). RESULTS: There were 8,051 patients with RA who were included: 81% were women, and the mean age was 76 years. Over a 2-year period, the mean number of peripheral joint MRIs per beneficiary was 0.3 (median 0 [range 0-50]), peripheral joint radiographs per beneficiary was 2.6 (median 1 [range 0-33]), and DXA scans per beneficiary was 0.7 (median 0 [range 0-11]). Only 6.8% of patients received >1 peripheral joint MRI, and 6% of HRRs had a mean number of peripheral joint MRIs >1. CONCLUSION: There is variation in the use of peripheral joint MRI, peripheral joint radiographs, and DXA scans among Medicare patients with RA, although only a small number of HRRs have consistently high utilization. Although we cannot judge the appropriateness of each procedure, variation in use across regions signals the need for investigations to examine potential overutilization.
28028685 RAPID3 scores and hand outcome measurements in RA patients: a preliminary study. 2017 Jun The Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported disease activity measure used to assess physical function, pain, and global health in patients with rheumatoid arthritis (RA) without formal joint counts. Since hand involvement and its decreased function are hallmarks of RA, the aim of our study was to investigate the performance of RAPID3 scores with regard to hand function and to confirm previous findings that the RAPID3 score as a disease activity measure is strongly correlated with the DAS28 score. Sixty-eight consecutive patients with RA (85% female), aged 18-75 years, were included in the study and were recruited during their outpatient visit. Apart from demographic and clinical data, the obtained parameters of interest included RAPID3 scores and assessments of the function of the hand, namely, the signal of functional impairment (SOFI)-hand, grip strength, and pulp-to-palm distance, as well the Health Assessment Questionnaire- Disability Index (HAQ-DI) and DAS28 scores. Pearson's correlation coefficient, Student's t test and linear regression were used in the statistical analysis of the results. The significance was set to p < 0.05. A positive correlation was found between RAPID3 scores and HAQ-DI scores, SOFI-hand scores, and pulp-to-palm distance, and negative correlation was observed between RAPID3 scores and grip strength. The order regarding the strength of correlations between RAPID3 scores and other variables (from the strongest to the weakest) was as follows: HAQ-DI, grip strength, SOFI-hand and pulp-to-palm distance. The hand assessment variables had stronger correlations with RAPID3 scores than with DAS28 scores. Our preliminary study showed that RAPID3 scores were strongly correlated with measurements of the functional ability of the hand, demonstrating that RAPID3 can be used as a measure of disease activity in clinical practice and to characterize hand function. Further studies are needed to confirm this result.
28333949 Metabolic syndrome and its components among rheumatoid arthritis patients: A comprehensive 2017 BACKGROUND: Estimating the current global prevalence of metabolic syndrome (MetS), and its components, among rheumatoid arthritis (RA) patients is necessary in order to formulate preventative strategies and to ensure there are adequate community resources available for these patients. Furthermore, the association between RA and MetS is controversial and has not previously been comprehensively assessed. Therefore, the present study aimed to: 1) determine the prevalence of MetS, and its components, among RA patients across the world 2) update the odds ratio of MetS in RA patients, compared to healthy controls, using a comprehensive systematic review and meta-analysis. METHODS: International databases, including: the Web of Science, PubMed, Scopus, Embase, CINAHL and other relevant databases were searched to identify English language articles which reported the prevalence and risk of MetS in RA patients between January 2000 and August 2016. The meta-analysis only included studies which clearly described the time and location of the study, utilised adequate sampling strategies, and appropriate statistical analyses. RESULTS: The meta-analyses of prevalence (70 studies [n = 12612]) and risk (43 studies [n = 35220]) of MetS in RA patients were undertaken separately. The overall pooled prevalence of MetS was 30.65% (95% CI: 27.87-33.43), but this varied from 14.32% (95% CI: 10.59-18.05) to 37.83% (95% CI: 31.05-44.61), based upon the diagnostic criteria used. The prevalence of MetS also varied slightly between males (31.94%, 95% CI: 24.37-39.51) and females (33.03%, 95% CI: 28.09-37.97), but this was not statistically significant. The overall pooled odds ratio (OR) of MetS in RA patients, compared to healthy controls, was 1.44 (95% CI: 1.20-1.74), but this ranged from 0.70 (95% CI: 0.27-1.76) to 4.09 (95% CI: 2.03-8.25), depending on the criteria used. The mean age and diagnostic criteria of MetS were identified as sources of heterogeneity in the estimated odds ratios between studies (P<0.05). CONCLUSIONS: According to the high prevalence of MetS in RA patients, and high risk of MetS, measuring metabolic syndrome in RA patients is strongly recommended. Furthermore, as high waist circumference (WC) is the most common metabolic syndrome component, more attention must be paid to nutrition and weight loss among those with RA.
28426705 An automated algorithm for the detection of cortical interruptions on high resolution peri 2017 OBJECTIVES: To introduce a fully-automated algorithm for the detection of small cortical interruptions (≥0.246mm in diameter) on high resolution peripheral quantitative computed tomography (HR-pQCT) images, and to investigate the additional value of manual correction of the automatically obtained contours (semi-automated procedure). METHODS: Ten metacarpophalangeal joints from seven patients with rheumatoid arthritis (RA) and three healthy controls were imaged with HR-pQCT. The images were evaluated by an algorithm according to the fully- and semi-automated procedure for the number and surface of interruptions per joint. Reliability between the fully- and semi-automated procedure and between two independent operators was tested using intra-class correlation coefficient (ICC) and the proportion of matching interruptions. Validity of single interruptions detected was tested by comparing it to visual scoring, as gold standard. The positive predictive value (PPV) and sensitivity were calculated. RESULTS: The median number of interruptions per joint was 14 (range 2 to 59) and did not significantly differ between the fully- and semi-automated procedure (p = 0.37). The median interruption surface per joint was significantly higher with the fully- vs. semi-automated procedure (respectively, 8.6mm2 vs. 5.8mm2 and 6.1mm2, p = 0.01). Reliability was almost perfect between the fully- and semi-automated procedure for both the number and surface of interruptions (ICC≥0.95) and the proportion of matching interruptions was high (≥76%). Also the inter-operator reliability was almost perfect (ICC≥0.97, proportion of matching interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from 69.7% to 76.3%. Most interruptions detected with the algorithm, did show an interruption on a 2D grayscale image. However, this interruption did not meet the criteria of an interruption with visual scoring. CONCLUSION: The algorithm for HR-pQCT images detects cortical interruptions, and its interruption surface. Reliability and validity was comparable for the fully- and semi-automated procedures. However, we advise the use of the semi-automated procedure to assure quality. The algorithm is a promising tool for a sensitive and objective assessment of cortical interruptions in finger joints assessed by HR-pQCT.