Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
27459020 Effectiveness of abatacept for patients with Sjögren's syndrome associated with rheumatoi 2016 Nov OBJECTIVE: To clarify the efficacy and safety of abatacept for secondary Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). METHODS: The primary endpoint of this open-labeled, prospective, observational multicenter study for secondary SS with RA was the remission rate of Simplified Disease Activity Index (SDAI) at 52 weeks after initiation of abatacept. The secondary endpoints included Saxon's test and Schirmer's test. Adverse events and adherence rate during the study period were also analyzed. RESULTS: Thirty-six patients (all females) were enrolled in this study. The mean SDAI decreased significantly from 20.6 ± 11.2 (±SD) at baseline to 10.0 ± 10.5 at 52 weeks (p < 0.05). Patients with SDAI remission increased from 0 (0 week) to 12 patients (33.3%) at 52 weeks. Saliva volume assessed by Saxon's test increased significantly from 2136 ± 1809 (0 week) to 2397 ± 1878 (24 weeks) mg/2 min (n = 34, p < 0.05). Saliva volume increased significantly from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min in 11 patients with Greenspan grade 1 or 2 of labial salivary gland biopsy (p < 0.05), but no change was noted in 18 patients with Greenspan grade 3 or 4. Tear volume by Schirmer's test increased significantly from 4.2 ± 4.8 (0 week) to 6.4 ± 7.8 (24 weeks) mm/5 min (n = 30, p < 0.05). The adherence rate to abatacept was 80.6% (29/36) over the 52-week period. Twelve adverse events occurred in 10 of the 36 patients, and 7 of these events were infections. CONCLUSION: Abatacept seems to be effective for both RA and SS related manifestations.
25510289 Effects of cigarette smoking on early arthritis: a cross-sectional study-data from the Arg 2015 May Our objective was to analyze the effects of cigarette smoking on disease activity, functional capacity, radiographic damage, serology and presence of extraarticular manifestations in patients with rheumatoid arthritis and undifferentiated arthritis. This is a cross-sectional study of 1,305 patients (729 with rheumatoid arthritis and 576 with undifferentiated arthritis) from CONAART, the Argentine Consortium for Early Arthritis that includes patients older than 16 years with <2 years of disease. Sociodemographic data, clinical characteristics of the disease and smoking history were collected. In patients with rheumatoid arthritis the disease activity score of 28 joints was 5.4 ± 1.3 in current smokers, 5.2 ± 1.4 in former smokers and 5.1 ± 1.4 in never smokers (p = 0.011). The simple erosion narrowing score was higher in current smokers and former smokers than in never smokers (M 14.0, R Q 6.0-21.0; M 15.0, R Q 7.0-24.0; M 10.0, R Q 5.0-17.0; p = 0.006). Current smokers had higher rheumatoid factor titer (M 160.0, R Q 80.0-341.0) than former smokers (M 146.8, R Q 6.03-255.5) and never smokers (M 15.0, R Q 9.0-80.0) (p = 0.004). The variable independently associated with tobacco exposure was simple erosion narrowing score (OR = 1.03, 95 % CI 1.00-1.05; p = 0.012). In patients with undifferentiated arthritis, an association between smoking status and parameters of activity or radiographic damage was not observed. Neither was tobacco exposure related to the presence of extraarticular manifestations or to the degree of disability in any of the two groups of patients. No relation was found between disease activity and severity, and number of packs smoked per year. Tobacco.
27437936 Meta-Analysis: Diagnostic Accuracy of Anti-Carbamylated Protein Antibody for Rheumatoid Ar 2016 OBJECTIVE: The anti-carbamylated protein (CarP) antibody is a novel biomarker that might help in the diagnosis of rheumatoid arthritis (RA). We aim to assess the diagnostic value of anti-CarP antibody for RA. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus for studies published by December 15, 2015. Studies in any language that evaluated the utility of the anti-CarP antibody in the diagnosis of RA in which healthy donors or patients without arthritis or arthralgia served as controls were included. Two investigators independently evaluated studies for inclusion, assessed study quality and abstracted data. A bivariate mixed-effects model was used to summarize the diagnostic indexes from 7 eligible studies. RESULTS: The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-CarP antibody were 42% (95% CI, 38% to 45%), 96% (95% CI, 95% to 97%), 10.2 (95% CI, 7.5 to 13.9), and 0.61 (95% CI, 0.57 to 0.65), respectively. The summary diagnostic odds ratio was 17 (95% CI, 12 to 24), and the area under summary receiver operator characteristic curve was 80% (95% CI, 77% to 84%). CONCLUSION: Anti-CarP antibody has a moderate value in the diagnosis of RA with high specificity but relatively low sensitivity.
26135850 KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheuma 2015 Dec Karyopherin-α2 (KPNA2) functions as an adaptor that transports several proteins to the nucleus. We investigated the function and possible mechanisms of KPNA2 involved in rheumatoid arthritis (RA). Western blotting and immunohistochemistry showed the protein expression of KPNA2 increased in synovial tissue of RA patients compared with the healthy controls. Double immunofluorescent staining indicated that KPNA2 co-localized with T cells, macrophage-like synoviocytes, fibroblast-like synoviocytes, and neutrophils in synovial tissue of RA patients. Moreover, the expression of KPNA2 in SW982 cells was increased in a time-dependent manner in response to TNFα stimulation. Both Western blotting and immunofluorescent staining assay revealed the co-localization of KPNA2 and P65 and their translocation from cytoplasma in TNFα-treated SW982 cells. Furthermore, knocking down the expression of KPNA2 by siRNA inhibited TNFα-induced expression of IL-6, MMP-1, and MMP-13 and, more importantly, decreased the P65 phosphorylation in SW982 cells. We therefore suggested that KPNA2 may play a key role in the inflammation process of RA via NF-κB P65 signal transduction pathway.
26271172 [Dose-reduction of TNF-α blockers in patients with rheumatoid arthritis]. 2015 Tumour-necrosis-factor alpha (TNF-α) blockers are highly effective in patients with rheumatoid arthritis, but their use is limited by the high costs of the drug: around € 10,000 to € 15,000 per patient per year. In a recent randomised study, it was shown that dose reduction, or even stopping the medication, was possible in 43% and 20% of patients, respectively; the percentage of patients with a major flare was comparable: 10% versus 12%. Another study, in patients with rheumatoid arthritis in clinical remission, showed no difference in response between patients continuing etanercept 50 mg per week and patients in whom the dosage was reduced to 25 mg per week. These studies suggest that dose-reduction is possible in a substantial number of patients with rheumatoid arthritis. It is not yet possible, however, to predict which individuals are at high risk for flares when reducing the dosage of TNF-α blocking agents.
27112144 Hearing impairment in patients with rheumatoid arthritis: association with anti-citrullina 2016 Sep It has been suggested that hearing impairment (HI) is one of the extra-articular features of rheumatoid arthritis (RA). Nevertheless, the prevalence and nature of HI in RA is still uncertain. The objectives were to study hearing function in patients with RA using audiometric tests and to examine whether HI correlates with autoantibodies. Hearing functions were investigated in 43 consecutive RA patients and 23 control subjects (less than 60 years old). Their sera were evaluated for the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and anti-mutated citrullinated vimentin (anti-MCV) antibodies. HI was observed in 46.5 % of RA patients and in 30.4 % of control subjects, p = 0.32. HI was characterized as sensorineural in 80 and 85.7 % of RA patients and control subjects with HI, respectively, p = 1.00. RA patients had a worse hearing threshold for air conduction at 6 kHz in the right ear (p = 0.019) and had a decreased amplitude of otoacoustic emissions (OAEs) at 2 kHz bilaterally (p = 0.04) compared with control subjects. In the RA group, patients with and without HI were 80 and 34.78 % anti-CCP positive, respectively, p = 0.008. RA patients with and without HI were 85 and 43.48 % anti-MCV positive, respectively, p = 0.013. HI in RA patients was mainly sensorineural and was associated with anti-CCP and anti-MCV antibodies.
26176566 Inhibition of B-cell apoptosis is mediated through increased expression of Bcl-2 in patien 2016 Feb AIM: Abnormal B-cell apoptosis is believed to have a role in rheumatoid arthritis (RA) pathogenesis, but the exact mechanisms of B-cell apoptosis in RA have not been elucidated. We therefore investigated the percentage of circulating B cells and its relationship with apoptosis in a cohort of patients with RA. METHODS: B cells were quantified by flow cytometry in RA patients and matched controls, and the relationships between these proportions and RA disease parameters were calculated. Rates of apoptosis were determined by annexin V/propidium iodine analysis, and Bcl-2 and caspase-3 protein levels were determined by western blot. RESULTS: RA patients had significantly higher percentage of B cells in the peripheral blood than healthy controls but a significantly lower rate of B-cell apoptosis. The percentage of B cells correlated with Disease Activity Score of 28 joints and serum immunoglobulin G concentration in RA patients. Expression of anti-apoptosis protein Bcl-2 was higher in RA patients than in healthy controls, whereas expression of apoptosis marker caspase-3 in B cells was lower. CONCLUSION: The higher percentage of B cells in the peripheral blood of RA patients may be due, at least partially, to disruption of the normal pathway of apoptosis in these cells. The inhibition of B-cell apoptosis in these patients may be attributable to the enhanced expression of Bcl-2 in these cells.
26457337 Pro musculoskeletal ultrasonography in rheumatoid arthritis. 2015 Jul Musculoskeletal ultrasound has become a widely used imaging diagnostic tool both in the use of daily clinical practice and for clinical studies in monitoring treatment efficiency and predicting disease outcome. By US, detection of inflammatory soft tissue and erosive bone lesions is possible. Grey-scale and power Doppler ultrasound examination is more sensitive and more reliable than clinical examination. Furthermore, patients with unclear arthritic symptoms can be better diagnosed for arthritis by US than by clinical examination. This article gives an overview about the use of US in the diagnosis of early arthritis, especially early rheumatoid arthritis, its role as a prognostic assessor (structural damage), as a monitor for treatment response, as an detector of "real" remission, and a guide to injection procedure.
26875450 Novel Immunotherapeutic Avenues for Rheumatoid Arthritis. 2016 Mar Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease. It leads to irreversible joint damage, physical handicap, and reduced life expectancy. The past two decades have seen considerable therapeutic advances with the development of biologic treatments to block proinflammatory cytokines or modulate lymphocyte function, followed by the development of small molecules to target intracellular signaling. Nevertheless, only a minority of patients can achieve disease remission, especially long term, warranting further investigation into newer therapeutic options. Targeting single proinflammatory pathways may not be sufficient, as suggested by variable results with T helper (Th)-17-related cytokine blockade. Multilevel information from 'omics' techniques along with data from mechanistic studies might facilitate the identification of pivotal checkpoints in RA disease pathogenesis and the subsequent development of new effective treatments.
27896420 Level of agreement between three-dimensional volumetric ultrasound and real-time conventio 2017 Feb The aim of the study was to assess agreement between three-dimensional volumetric ultrasound (3D US) performed by inexperienced staff and real-time conventional ultrasound (2D US) performed by experienced rheumatologists in detecting and scoring rheumatoid arthritis (RA) lesions. Thirty-one RA patients underwent examination of seven joints by 2D and 3D US for synovitis and tenosynovitis in B and PD modes and erosions in B mode. A global score for synovitis and global counts for synovitis, tenosynovitis and erosions were also calculated for every patient. Agreement between 2D and 3D US was analysed for counts and scores at the patient level with the intraclass correlation coefficient (ICC) and for counts at the joint level with Cohen's kappa coefficient. B-mode synovitis was detected at a median of five joints in each patient, frequently in wrists and hand joints but less frequently in foot joints. PD-mode synovitis, tenosynovitis and erosions were detected less frequently. All ICCs for agreement between 2D and 3D US findings were significant. All kappa coefficients were significant for B- and PD-mode synovitis and for erosions (except PIP3), while those for tenosynovitis were only significant for MCP2 (B and PD modes) and PIP2 (B mode). Although the 3D US volumes were acquired by inexperienced operators, agreement between 2D and 3D US was acceptable in detecting and scoring synovitis. A higher level of agreement was attained for patient-level global scores and counts than for individual joints.
27561027 [Frailty syndrome in patients with rheumatoid arthritis]. 2016 BACKGROUND: Rheumatoid arthritis (RA) is a chronic disabling disease, which leads to joint destruction and functional limitations. It diminishes health-related quality of life (HRQoL) and life expectancy. Frailty is a chronic inflammatory process related to aging that causes disability and affects HRQoL. The presence of comorbidity and polypharmacy are both related to RA severity. The aim of this study was to assess the prevalence of frailty and comorbidities in patients with RA. METHODS: Based on the American College of Rheumatology (ACR) criteria, we studied patients with RA that were seen at the outpatient clinic of the Rheumatology Department of a third level hospital. We applied the frailty criteria according to the Cardiovascular Health Study. We registered demographic data along with comorbidities and polypharmacy, using a cross-sectional, observational, and descriptive study design. RESULTS: Five hundred consecutive RA patients were included, 453 (90.6 %) were female.Mean age was 51.3 years and mean disease duration was 13.2 years; 23.4 % met frailty criteria. Mean number of comorbidities was 1.59, with systemic hypertension and obesity as the most frequent ones (25.2 % and 18.2 %, respectively). Polypharmacy was found in 99.6 % and 69.6 % received more than five drugs simultaneously. CONCLUSIONS: Prevalence of frailty in this study was unexpectedly high and so were comorbidities and multiple drug usage. Clinicians should make an early detection of signs of frailty and comorbidity in RA patients.
26658904 Association of Killer Cell Immunoglobulin- Like Receptor Genes in Iranian Patients with Rh 2015 OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by persistent synovitis, ultimately leading to cartilage and bone degeneration. Natural Killer cells and CD28 null T-cells are suspected as role players in RA pathogenesis. These cells are similar in feature and function, as they both exert their cytotoxic effect via Killer Cell Immunoglobulin- Like Receptors (KIR) on their surface. KIR genes have either an inhibitory or activating effect depending on their intracytoplasmic structure. Herein we genotyped 16 KIR genes, 3 pseudo genes and 6 HLA class І genes as their corresponding ligands in RA patients and control subjects. METHODS: In this case-control study, KIR and HLA genes were genotyped in 400 RA patients and 372 matched healthy controls using sequence-specific primers (SSP-PCR). Differences in the frequency of genes and haplotypes were determined by χ² test. RESULTS: KIR2DL2, 2DL5a, 2DL5b and activating KIR: KIR2DS5 and 3DS1 were all protective against RA. KIR2DL5 removal from a full Inhibitory KIR haplotype converted the mild protection (OR = 0.56) to a powerful predisposition to RA (OR = 16.47). Inhibitory haplotype No. 7 comprising KIR2DL5 in the absence of KIR2DL1 and KIR2DL3 confers a 14-fold protective effect against RA. CONCLUSION: Individuals carrying the inhibitory KIR haplotype No. 6 have a high potential risk for developing RA.
27801338 [The correlations of single photon emission computed tomography joints scan and bone metab 2016 Nov 1 Objective: To explore the correlation between quantitative value of joint bone scan by single photon emission computed tomography(SPECT) and serum bone metabolic markers in patients with active rheumatoid arthritis(RA). Method: Clinical data of 60 newly diagnosed RA patients were retrospectively collected in Department of Rheumatology and Immunology from May 2013 to December 2014, including 28 cases with medical history less than 6 months and 32 from 6 months to 2 years. Serum C-terminal telopeptide of type Ⅰ collgen(CTX-Ⅰ)and N-terminal propeptide of type Ⅰ collagen(PINP)were tested by chemiluminesence. SPECT whole body bone and target joint scan before treatment was done. Thirty-nine healthy subjects as control group received ultrasound, electrocardiogram, X-ray, and whole body bone imaging examination. Quantitative values of joint imaging were calculated for the statistical analysis. Result: Demographic data between RA group and control group were comparable (P>0.05), including sample, sex, age and BMI. The joint SPECT value, CTX-Ⅰ and PINP levels were all significantly higher than those of control group (P<0.01), which were 6.48±1.98 versus 3.73±1.16; (0.66±0.37) mg/L versus (0.58±0.21) mg/L; (46.35±28.15) mg/L versus (30.47±13.75) mg/L respectively. Joint SPECT values had positive correlations with serum CTX-Ⅰ levels in all RA patients, as well as PINP in patients with disease duration 6mon-2years. And the according correlation coefficients were 0.513, 0.495, 0.402(P<0.05). But SPECT value had no correlation with CTX-Ⅰ (P=0.081) in patients with disease duration less than 6 mon.The correlation coefficient was 0.336. Conclusion: SPECT imaging quantitative values were positively correlated with serum bone metabolic parameters. Thus SPECT imaging alone or combined with bone markers are helpful in diagnosing active RA.
26711533 Disease-Regulated Gene Therapy with Anti-Inflammatory Interleukin-10 Under the Control of 2016 Mar Disease-inducible promoters for the treatment of rheumatoid arthritis (RA) have the potential to provide regulated expression of therapeutic proteins in arthritic joints. In this study, we set out to identify promoters of human genes that are upregulated during RA and are suitable to drive the expression of relevant amounts of anti-inflammatory interleukin (IL)-10. Microarray analysis of RA synovial biopsies compared with healthy controls yielded a list of 22 genes upregulated during RA. Of these genes, CXCL10 showed the highest induction in lipopolysaccharide-stimulated synovial cells. The CXCL10 promoter was obtained from human cDNA and cloned into a lentiviral vector carrying firefly luciferase to determine the promoter inducibility in primary synovial cells and in THP-1 cells. The promoter activation was strongest 8-12 hr after stimulation with the proinflammatory cytokine tumor necrosis factor (TNF)-α and was reinducible after 96 hr. In addition, the CXCL10 promoter showed a significant response to RA patient serum, compared with sera from healthy individuals. The luciferase gene was replaced with IL-10 to determine the therapeutic properties of the CXCL10p-IL10 lentiviral vector. Primary synovial cells transduced with CXCL10p-IL10 showed a great increase in IL-10 production after stimulation, which reduced the release of proinflammatory cytokines TNF-α and IL-1β. We conclude that the selected proximal promoter of the CXCL10 gene responds to inflammatory mediators present in the serum of patients with RA and that transduction with the lentiviral CXCL10p-IL10 vector reduces inflammatory cytokine production by primary synovial cells from patients with RA. CXCL10 promoter-regulated IL-10 overexpression can thus provide disease-inducible local gene therapy suitable for RA.
26015084 Characteristics of hand involvement in a comparative study of two early RA cohorts from th 2017 Oct AIM: To compare the characteristics of early hand involvement in rheumatoid arthritis (RA) using two matched populations, from the UK and China. METHODS: A cohort comparison study was conducted. Sixty Chinese patients recruited from Shanghai, China were matched on gender and age with 60 patients from a prospective early RA cohort from the UK (SARAH trial). The procedures of data collection in China followed the standard operating procedures employed in the SARAH trial. Outcome measures including Michigan Hand Outcomes Questionnaire (MHQ), medication history and physical assessments were used to assess functional ability and hand impairment. RESULTS: UK patients reported significantly more hand pain (P = 0.015), less satisfaction with dominant hand performance (P  = 0.040), more swollen and tender joints (P = 0.016 and P = 0.001) and greater dexterity of both dominant and non-dominant hands (P < 0.001 and P < 0.001), while Chinese patients had higher disease activity indicated by erythrocyte sedimentation rate and C-reactive protein, more rheumatoid factor, less satisfaction in both dominant and non-dominant hand appearances (P < 0.001 and P < 0.001, respectively) and greater dominant hand deformity (P  = 0.003). No statistically significant differences were seen in range of movement and overall hand function as reported by the MHQ. CONCLUSION: The severity of RA is not milder in China than in the UK and the characteristics of hand involvement tend to be different. Clinicians should consider country-specific differences in managing pain and delivering treatment. It would be helpful for a future study to investigate the RA impact characteristics on a wider range of patients both from within China and from other populations.
26849891 Mapping health assessment questionnaire disability index (HAQ-DI) score, pain visual analo 2016 Apr The aim of this study was to estimate the mapping model for EuroQol-5D (EQ-5D) utility values using the health assessment questionnaire disability index (HAQ-DI), pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) in a large, nationwide cohort of rheumatoid arthritis (RA) patients in Korea. The KORean Observational study Network for Arthritis (KORONA) registry data on 3557 patients with RA were used. Data were randomly divided into a modeling set (80 % of the data) and a validation set (20 % of the data). The ordinary least squares (OLS), Tobit, and two-part model methods were employed to construct a model to map to the EQ-5D index. Using a combination of HAQ-DI, pain VAS, and DAS28, four model versions were examined. To evaluate the predictive accuracy of the models, the root-mean-square error (RMSE) and mean absolute error (MAE) were calculated using the validation dataset. A model that included HAQ-DI, pain VAS, and DAS28 produced the highest adjusted R (2) as well as the lowest Akaike information criterion, RMSE, and MAE, regardless of the statistical methods used in modeling set. The mapping equation of the OLS method is given as EQ-5D = 0.95-0.21 × HAQ-DI-0.24 × pain VAS/100-0.01 × DAS28 (adjusted R (2) = 57.6 %, RMSE = 0.1654 and MAE = 0.1222). Also in the validation set, the RMSE and MAE were shown to be the smallest. The model with HAQ-DI, pain VAS, and DAS28 showed the best performance, and this mapping model enabled the estimation of an EQ-5D value for RA patients in whom utility values have not been measured.
25603041 The role of the synovial fibroblast in rheumatoid arthritis pathogenesis. 2015 Mar PURPOSE OF REVIEW: Synovial fibroblasts continue to grow in prominence both as the subjects of research into the pathogenesis of rheumatoid arthritis and as novel therapeutic targets. This timely review aims to integrate the most recent findings with existing paradigms of fibroblast-related mechanisms of disease. RECENT FINDINGS: Linking the role of synovial fibroblasts as innate sentinels expressing pattern recognition receptors such as toll-like receptors to their effector roles in joint damage and interactions with leukocyte subpopulations has continued to advance. Understanding of the mechanisms underlying increased fibroblast survival in the inflamed synovium has led to therapeutic strategies such as cyclin-dependent kinase inhibition. Major advances have taken place in understanding of the interactions between epigenetic and micro-RNA regulation of transcription in synovial fibroblasts, improving our understanding of the unique pathological phenotype of these cells. Finally, the impact of new markers for fibroblast subpopulations is beginning to become apparent, offering the potential for targeting of pathological cells as the roles of different populations become clearer. SUMMARY: Over the past 2 years, major advances have continued to emerge in understanding of the relationship between synovial fibroblasts and the regulation of inflammatory pathways in the rheumatoid arthritis synovium.
27729613 MicroRNA-126 affects rheumatoid arthritis synovial fibroblast proliferation and apoptosis 2016 Nov 8 Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and destruction of the joints as well as an increased risk of cardiovascular disease. RA synovial fibroblasts (RASFs) are involved in the progression of RA and release pro-inflammatory cytokines. On the other hand, microRNAs (miRs) may help control the inflammatory response of immune and non-immune cells. Therefore, our study used lentiviral expression vectors to test the effects of miR-126 overexpression on RASF proliferation and apoptosis. Luciferase experiments verified the targeting relationship between miR-126 and PIK3R2 gene. The co-transfection of anti-miR-126 and PIK3R2 siRNA to RASFs were used to identify whether PIK3R2 was directly involved in proliferation and apoptosis of miR-126-induced RASFs. Real-time polymerase chain reaction (PCR) was used to detect miR-126 and PIK3R2 expressions. MTT assay was used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis and cell cycle. Western blotting was used to detect PIK3R2, PI3K, AKT and p-AKT proteins. After Lv-miR-126 infected RASFs, the relative expression of miR-126 was significantly enhanced. MiR-126 promoted RASF proliferation and inhibited apoptosis. Levels of PIK3R2 decreased while total PI3K and p-AKT levels increased in RASFs overexpressing miR-126. Co-transfection of anti-miR-126 and PIK3R2 siRNA also increased PI3K and p-AKT levels as well as RASF proliferation and reduced apoptosis, as compared to anti-miR-126 treatment alone. Finally, luciferase reporter assays showed that miR-126 targeted PIK3R2. Our data indicate that miR-126 overexpression in RASFs inhibits PIK3R2 expression and promotes proliferation while inhibiting apoptosis. This suggests inhibiting miR-126 may yield therapeutic benefits in the treatment of RA.
27457311 Efficacy and safety of golimumab in Indian patients with rheumatoid arthritis: Subgroup da 2016 Nov AIM: To conduct a subgroup analysis of GO-MORE trial Part 1, comparing efficacy and safety of add-on subcutaneous golimumab therapy in rheumatoid arthritis (RA) patients enrolled from and outside India. METHODS: GO-MORE was an open-label, multicenter, prospective trial of add-on golimumab in biologic-naïve RA patients, having active disease despite being on conventional DMARD regimen(s). Part 1 of the study was chosen as the focus of this subgroup analysis because a substantial number of Indian patients (106) were enrolled compared to no Indian patients in Part 2. The primary efficacy outcome was proportion of patients achieving good to moderate DAS28-ESR (Disease Activity Score of 28 joints calculated using erythrocyte sedimentation rate) European League Against Rheumatism (EULAR) response at month 6. RESULTS: Efficacy evaluable population comprised of 105 and 3175 patients from India and outside India, respectively. Safety analysis included 106 patients enrolled from India and 3251 from outside India. A higher proportion of Indian patients had a high disease activity as measured by DAS28 ESR than outside India patients. At month 6, the proportion of Indian and non-Indian patients achieving DAS28-ESR, DAS28 - C-reactive protein, simplified disease activity index (SDAI) remission, and EuroQoL Quality-of-Life Questionnaire (EQ-5D) scores were comparable. Incidence of all adverse events was lower in Indian patients. There were no deaths, cases of tuberculosis or malignancy reported in the patients from India at month 6. CONCLUSIONS: The efficacy and safety results with add-on golimumab were consistent between RA patients from India and outside India, despite high baseline disease activity in the Indian patients.
25722062 Promoting physical activity in rheumatoid arthritis: a narrative review of behaviour chang 2015 PURPOSE: Despite physical activity having significant health benefits for people with rheumatoid arthritis (RA), current levels of physical activity in this population are suboptimal. Changing behaviour is challenging and interventions aimed at increasing physical activity in this context have had varying levels of success. This review provides an overview of common behaviour change theories used in interventions to promote physical activity and their application for promoting physical activity in people with RA. METHOD: A scoping, narrative review was conducted of English language literature, using the search terms "physical activity/exercise" and keywords, which are associated with behaviour change interventions. The theoretical basis of such interventions in people with RA was assessed using the "theory coding scheme". RESULTS: Six theories which have been used in physical activity research are discussed. Further, four studies which aimed to increase physical activity levels in people with RA are explored in detail. CONCLUSIONS: To date, behaviour change interventions conducted in RA populations to increase physical activity levels have not had a strong theoretical underpinning. It is proposed that an intervention utilising the theory of planned behaviour is developed with the aim of increasing physical activity in people with RA. Implications for Rehabilitation Interventions to promote physical activity in the rheumatoid arthritis (RA) population have failed to change participants' behaviour. A small number of studies have used behaviour change theories in the development and delivery of interventions. The theory of planned behaviour is recommended as the theoretical basis for an intervention to promote physical activity in the RA population.