Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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30945669 | Genetic and expression changes in TNF-α as a risk factor for rheumatoid arthritis pathoge | 2019 Mar | Antitumour necrosis factor-alpha (TNF-α) therapy is used as a clinical intervention for rheumatoid arthritis (RA) but differences exist in response to the treatment which makes the candidature of the screening of TNF-α alteration(s) at genetic and expression levels an important agenda prior to treatment. This study aims to determine the associative role of TNF-α -308G/A polymorphism and differential expression of TNF-α in the pathogenesis of RA. A case-control study where a total of 126 RA patients were enrolled based on ACR-EULAR (2010) criteria, along with 160 community matched age and sex controls over a period of three years. The differential expression level of TNF-α mRNA and protein level was studied and TNF-α -308G/A polymorphism was screened by T-ARMS PCR assay. All statistical analysis was performed using SPSS software. mRNA expression level of TNF-α was upregulated in RA cases (avg. 15.85 ± 9.52 fold) compared to control. TNF-α protein level was found to be higher in RA cases (28.62±7.17 pg/mL) compared to control (23.14±6.91 pg/mL). TNF-α -308 variant GA genotype was higher in RA (46.03%) than in control (25%). The presence of TNF-α -308 variant A allele was associated with increased risk of RA susceptibility (odds ratio (OR) = 2.559 at 95% confidence interval (CI), P< 0.001) but not severity (OR = 1.617 at 95% CI, P = 0.571). The presence of -308 variant genotype was associated with a higher TNF-α mRNA and protein expression. The presence of TNF-α -308A allele is associated with increased risk of RA susceptibility and differential TNF-α expression, and has prognostic significance. Association of higher TNF-α pro-inflammatory cytokine levels with northeast Indian patients makes them suitable subjects for anti-TNF-α therapy. | |
30710354 | Causal association between body mass index and risk of rheumatoid arthritis: A Mendelian r | 2019 Apr | OBJECTIVE: This study aimed to examine whether body mass index (BMI) is causally associated with rheumatoid arthritis (RA). METHOD: A two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median and MR-Egger regression methods was performed. We used the publicly available summary statistics data sets of genome-wide association studies (GWAS) meta-analyses for BMI in individuals of European descent (n = 322 154; GIANT consortium) as the exposure and a GWAS for noncancer illness code self-reported: RA from the individuals included in the UK Biobank (total n = 337 159; case = 7480, control = 329 679) as the outcome. RESULTS: We selected 68 single nucleotide polymorphisms at genome-wide significance from GWASs on BMI as the instrumental variables. The IVW method showed evidence to support a causal association between BMI and RA (beta = 0.003, SE = 0.001, P = 0.033). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = -3.54E-05; P = 0.736), but it showed no causal association between BMI and RA (beta = 0.004, SE = 0.004, P = 0.302). However, the weighted median approach yielded evidence of a causal association between BMI and RA (beta = 0.006, SE = 0.002, P = 0.004). Cochran's Q test and the funnel plot indicated no evidence of heterogeneity and asymmetry, indicating no directional pleiotropy. CONCLUSION: The results of MR analysis support that BMI may be causally associated with an increased risk of RA. | |
31099191 | Infection risks of rituximab versus non-rituximab treatment for rheumatoid arthritis: A sy | 2019 Aug | OBJECTIVE: The aim of this study was to assess the differences in infection rates between rituximab (RTX) and non-RTX treatment in patients with rheumatoid arthritis (RA). METHODS: A systematic review and meta-analysis was conducted by searching databases of PubMed, MEDLINE, EMBASE, Web of Science and Cochrane Library through to June 2018. We included studies that compared RTX and non-RTX treatment for patients with RA. Outcome measures were overall infections and serious infections between RTX and non-RTX treatments. RESULTS: A total of 11 articles, including 9502 patients (4595 with RTX treatment and 4907 with non-RTX treatment) met our inclusion criteria. The results demonstrated that RTX-related all infections and serious infections in RA patients were 43.8% and 4.4%, respectively. Pooled analysis showed no significant differences between RTX and non-RTX treatment groups in overall infections rate (43.3% vs 44.9%; odds ratio [OR]Â =Â 0.87; 95% CIÂ =Â 0.70-1.08) and serious infections rate (4.1% vs 4.6%; ORÂ =Â 1.05; 95% CIÂ =Â 0.84-1.31). Subgroup analysis also showed no significant differences in overall infections between RTX versus placebo (ORÂ =Â 0.98, 95% CIÂ =Â 0.71-1.33); RTX versus tumor necrosis factor inhibitors (TNFi) (ORÂ =Â 0.47, 95% CIÂ =Â 0.30-1.73); RTX plus methotrexate (MTX) versus placebo plus MTX (ORÂ =Â 0.98, 95% CIÂ =Â 0.77-1.24), and in serious infections between RTX versus placebo (ORÂ =Â 1.06, 95% CIÂ =Â 0.36-3.07); RTX versus TNFi (ORÂ =Â 1.25, 95% CIÂ =Â 0.96-1.63); RTX plus MTX versus placebo plus MTX (ORÂ =Â 0.69, 95% CIÂ =Â 0.39-1.20). CONCLUSION: In patients with RA, RTX treatment has no additional risks for infections over non-RTX treatment. | |
30418118 | Aromatic hydrocarbon receptor provides a link between smoking and rheumatoid arthritis in | 2019 May | OBJECTIVES: Epidemiology shows that smoking plays a central role in rheumatoid arthritis (RA). The aim of this study was to evaluate the potential relationship between smoking, aromatic hydrocarbon receptor (AHR) and RA susceptibility. METHODS: We performed a hospital-based, case-control study of patients with RA and healthy controls. Expressions of AHR, cytochrome P4501A1(CYP1A1), aromatic hydrocarbon receptor repressor (AHRR) genes were assessed in peripheral blood mononuclear cells (PBMCs) and cultured cells using real-time PCR. The response of PBMCs to the AHR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cigarette smoke extract (CSE) were cultured in vitro. RESULTS: AHR and its downstream gene expressions were demonstrated in smoking rheumatoid PBMCs and non-smoking patients with significantly higher expression in smoking patients. The observation was consistent with the sensitivity of RA PBMCs to TCDD and CSE stimulation demonstrated in vitro. CONCLUSIONS: Our study shows that smoking may be involved in the pathogenesis of RA by the AHR pathway. | |
30417444 | The triptolide-induced apoptosis of osteoclast precursor by degradation of cIAP2 and treat | 2019 Feb | This study aims to discuss the effect of triptolide (TPL) on rheumatoid arthritis (RA) and the mechanism related to osteoclast precursor (OCP) and osteoclast (OC). TNF-transgenic RA mice were treated with different doses of TPL by gavage. After the administration was finished, the curative effects were evaluated and compared, and the OCP apoptosis rates, the OC number, and the OC differentiation ability in vitro were detected. Finally, splenocytes of wild-type mice were cultured in vitro and induced to differentiate into OCP, and the cell apoptosis rate, cIAP2, and apoptotic effectors expression level were detected after cIAP2 overexpression and TPL administration. After TPL administration, the RA symptoms in the TPL groups were all better, the apoptosis rate of OCP was higher, and the amount of OC in vitro were lower than that in the control group (all PÂ <Â 0.05), and all of the changes in the high-dose group were more obvious than the low-dose group. In splenocytes cells cultured in vitro, cIAP2 overexpression could decrease the apoptosis rate of OCPs and increase the OC number, and TPL treatment could down-regulate the cIAP2 and promote OCP apoptosis and OC reduction. In conclusion, TPL could induce OCP apoptosis and inhibit OC formation to effectively treat RA by mediating cIAP2 degradation. | |
30251481 | Importance of Measuring Hand and Foot Function Over the Disease Course in Rheumatoid Arthr | 2019 Feb | OBJECTIVE: To assess function using the Signals of Functional Impairment (SOFI) instrument over 8 years, to study clinical variables associated with the change, and to study change over time of the SOFI items. METHODS: In total, 1,223 patients with early rheumatoid arthritis (RA) from the Better Anti-Rheumatic Farmacotherapy (BARFOT) cohort (mean ± SD age 56.9 ± 15.4 years, 67% women) were included in the analysis. Data from baseline and from 1 and 8 years were studied. The SOFI instrument includes measures of range of motion in the hand, shoulder/arm, and lower extremity (range 0-44, best to worst). The effects of baseline variables (sociodemographic, disease activity, joint destruction, and function) on change in SOFI scores were studied by linear regression analysis. RESULTS: During the first year, the improvement in mean ± SD SOFI scores was 2.7 ± 5.7 (P < 0.001). Worse scores in the Disease Activity Score in 28 joints and Health Assessment Questionnaire score at baseline were associated with this improvement (r(2) ≤ 0.11). During the next 7 years, the deterioration in SOFI scores was mean ± SD 1.5 ± 4.9 (P < 0.001). Based on change scores, we found that finger flexion, pincer grip, and toe-standing were the most important items to measure, explaining 58-61% of the total SOFI score, and these items were also associated with radiographic changes at the 8-year follow-up. CONCLUSION: Function as assessed with SOFI scores improved during the first year in patients with early RA, but it deteriorated slowly thereafter. Impaired hand and foot function was associated with joint destruction at the 8-year follow-up. Measures of hand and foot function will complement self-reported and medical data, both in clinical work and in long-term research studies. | |
31049760 | Association of cumulative anti-cyclic citrullinated protein antibodies with radiographic p | 2019 Sep | INTRODUCTION: Antibody against cyclic citrullinated protein (ACPA) is counted as one of the most important biomarkers in diagnosis, classification, and prognosis of rheumatoid arthritis (RA). We examined the evolution of ACPA during disease course and assess predictive value of time-weighted cumulative ACPA titer on radiographic progression in RA patients. METHOD: A group of 734 patients with RA was followed longitudinally over 2 years, with annual measurements of ACPA. The cumulative titers of ACPA were calculated using the trapezoidal rule and were divided into three categories: negative, low-to-moderate, and high. Radiographs of the hands were scored with the modified Sharp score (SHS). Multivariable logistic regression models were performed to identify independent predictors over follow-up for individual patients with different combinations of risk factors. The effect size was computed by Cohen's d method. RESULTS: The patients with radiographic progression had a higher SHS at baseline; and smoking status, diabetes, RF positivity, and use of biologic DMARDs were independently associated with radiographic progression (all P < 0.05). As for ACPA, reversion happened more commonly in men and was associated with younger onset age and lower titer at baseline, but it had no direct relevance to radiographic outcome. In multivariable regression analysis, only high cumulative or baseline titer of ACPA had a predictive power for rapid radiographic progression (all P < 0.05), and cumulative ACPA titer was superior in terms of statistical significance (Cohen's d, 0.637 versus 0.583). CONCLUSIONS: High cumulative ACPA titer was independently associated with accelerated radiographic progression, especially with initiation of joint damage. | |
30831253 | Compendium of synovial signatures identifies pathologic characteristics for predicting tre | 2019 May | Rheumatoid arthritis (RA) is therapeutically challenging due to patient heterogeneity and variability. Herein we describe a novel integration of RA synovial genome-scale transcriptomic profiling of different patient cohorts that can be used to provide predictive insights on drug responses. A normalized compendium consisting of 256 RA synovial samples that cover an intersection of 11,769 genes from 11 datasets was build and compared with similar datasets derived from OA patients and healthy controls. Differentially expression genes (DEGs) that were identified in three independent methods were fed into functional network analysis, with subsequent grouping of the samples based on a non-negative matrix factorization method. RA-relevant pathway activation scores and four machine learning classification techniques supported the generation of a predictive model of patient treatment response. We identified 876 up-regulated DEGs including 24 known genetic risk factors and 8 drug targets. DEG-based subgrouping revealed 3 distinct RA patient clusters with distinct activity signatures for RA-relevant pathways. In the case of infliximab, we constructed a classifier of drug response that was highly accurate with an AUC/AUPR of 0.92/0.86. The most informative pathways in achieving this performance were the NFκB-, FcεRI- TCR-, and TNF signaling pathways. Similarly, the expression of the HMMR, PRPF4B, EVI2A, RAB27A, MALT1, SNX6, and IFIH1 genes contributed in predicting the patient outcome. Construction and analysis of normalized synovial transcriptomic compendia can provide useful insights for understanding RA-related pathway involvement and drug responses for individual patients. | |
30175668 | Evaluation of factors associated with locomotive syndrome in Japanese elderly and younger | 2019 Sep | Objectives: We aimed to determine the prevalence of locomotive syndrome (LS) using the 25-question geriatric locomotive function scale (GLFS-25) and identify factors associated with LS in elderly and younger patients with rheumatoid arthritis (RA). Methods: Overall, 390 patients with RA who underwent GLFS-25 measurement, bone mineral density determination, and bioelectrical impedance analysis were enrolled. Factors associated with LS were analyzed by comparing patients with and without LS among both elderly and younger patients with RA. Results: The prevalence of LS was 41.5%, 47.7% and 32.3% in all patients, elderly patients, and younger patients with RA, respectively. Pain visual analog scale (VAS) and Health Assessment Questionnaire Disability Index (HAQ-DI) were associated with LS in both elderly and younger patients. Moreover, in younger patients with RA, disease activity score in 28 joints (DAS28), erythrocyte sedimentation rate (ESR), basal metabolic rate, and legs muscle mass were identified as being associated with LS. Conclusion: This study demonstrated that to prevent LS, we should aim to control pain and maintain a low HAQ-DI in elderly and younger patients with RA, and improve disease activity and maintain a higher basal metabolic rate, and legs muscle mass in younger patients with RA. | |
30654405 | [Guideline-Orientated Prescription of Disease-Modifying Drugs in Patients with Rheumatoid | 2019 Jun | BACKGROUND: With the market entry of biologics, the treatment of rheumatoid arthritis (RA) has changed fundamentally in terms of efficacy and costs. THE AIM: of this study is to analyse the treatment according the guideline of the German society of rheumatology for RA patients with disease-modifying anti-rheumatic drugs (DMARDs) using claims data from the statutory health insurance. MATERIALS AND METHODS: The claims data of the Techniker Krankenkasse were analysed retrospectively for the years 2011 - 2014. Subgroup analyses were used to conduct prescription and treatment differences with respect to guideline-recommended conventional DMARDs and biologics. RESULTS: The study population included 55,538 RA patients (29.7 % incidence, 70.3 % prevalence, 22.3 % M05: Seropositive rheumatoid arthritis, 77.7 % M06: Other rheumatoid arthritis). Only 21,616 insured patients (38.9 %) were prescribed a guideline-recommended conventional DMARD or biologic at least once within one year of/after the first diagnosis. Among incident patients, the coverage rate with disease-modifying drugs was below the prevalence patients (31.5 % vs. 42.1 %). 60.9 % of M05 patients and only 29.7 % of M06 patients received a single DMARD after index diagnosis. If a DMARD has been prescribed, then it was prescribed, on average, within the first quarter of the initial diagnosis. The leading role in the prescription of basic therapies for index medication is provided by the rheumatologist. Nevertheless, 68.3 % of patients consulted a specialist in rheumatology at least once within a year of the first diagnosis. CONCLUSION: The results of this large sample show differences in the guideline recommended prescription of disease-modifying drugs for different subgroups of RA as well as an undersupply in patients not treated by the rheumatologist. | |
29481842 | A novel gene and pathway-level subtyping analysis scheme to understand biological mechanis | 2019 May | Complex diseases have heterogeneous underlying molecular mechanisms. In order to improve the diagnosis and treatment of disease, it is vital to stratify patients into homogeneous subgroups that share a similar disease etiology. In this study, we performed gene-level subtyping analysis on two independent Rheumatoid Arthritis gene expression cohorts from different ethnic groups to discover the possible disease mechanisms associated with each subtype. Also, a novel pathway-level analysis is proposed to increase the subtyping robustness and facilitate biological interpretation. This approach could stratify RA patients into two robust and homogeneous groups with differing activation of central signal transduction pathways and pro-inflammatory cytokines in the pathogenesis of RA. Such a methodology can help understand disease mechanisms at play in different patient sub-populations and also potentially explain why some patients don't respond to anti-TNF treatment. | |
30620765 | Mortality, disability, and healthcare expenditure of patients with seropositive rheumatoid | 2019 | BACKGROUND: We investigated the mortality and disability rate, as well as the healthcare expenditure, for patients with newly diagnosed seropositive rheumatoid arthritis (RA) who were followed-up for up to 10 years, compared to the general population in Korea. METHODS: We conducted a nationwide population-based study using a National Health Insurance Service-National Sample Cohort of the Korean population, consisting of 1 million individuals who submitted medical care claims between 2002 and 2013. RA was identified using as the International Classification of Diseases code M05 (seropositive RA), with prescription of any disease-modifying anti-rheumatic drug (DMARD). Our analysis was based on the data of 1655 patients with incident seropositive RA and 8275 non-RA controls. The controls were matched to the RA cohort by sex, age at the time of diagnosis, duration of follow-up, geographic region, type of social security, and household income. RESULTS: The most commonly used conventional synthetic DMARDs were hydroxychloroquine (71.30%) and methotrexate (69.5%), with adalimumab being the most commonly used biologic DMARD (2.54%). The mortality rate was significantly higher in the RA than the control group (incidence rate ratio [IRR] 1.29, 95% confidence interval [CI] 1.02-1.64) in the first 10 years after diagnosis. Specifically, mortality due to infectious diseases (IRR 4.41, 95% CI 1.60-12.17) and pneumonia (IRR 3.92, 95% CI 1.46-10.53) was significantly higher in the RA than control group. The disability rate was higher in the RA than control group over the first 10 years of the disease (IRR 2.27, 95% CI 1.77-2.92), which was attributed to a higher incidence of physical disability (IRR 3.81, 95% CI 2.81-5.15). Annual health expenditure was greater for the RA than the control group. CONCLUSIONS: Therefore, the rate of mortality and disability, as well as healthcare expenditure, are higher for patients with RA over the first 10 years of the disease onset, than the general population of Korea. The use of claim data has limited the quality of information and there is a limit to the observation period, and we expect the prospective national-wide multicenter cohort for longer period to overcome these limitations. | |
31219665 | Comparison of Female Sexual Function Index in patients with psoriatic and rheumatoid arthr | 2019 Sep | OBJECTIVE: The aim of the recent study was to identify and compare the Female Sexual Function Index (FSFI) of three female populations: those with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and healthy individuals. METHODS: In this descriptive correlational study, convenience sampling was used to recruit 50 female RA patients, 36 female PsA patients and 50 healthy women between June and September 2018. RESULTS: The mean ages of the RA patients, PsA patients and healthy controls were, respectively, 53.1 ± 11.8 years, 51.6 ± 13.7 years and 37.4 ± 10.4 years. Controls were significantly younger than RA (p < 0.001) and PsA (p = 0.002) patients. Data including all participants: Based on the total sexual functioning cut-off score of 26.55, 68% of RA patients (34/50), 67% of PsA patients (22/33) and 44% of healthy controls (11/25) met the criteria for sexual dysfunction. Data excluding participants who reported not having had sex in the previous month: Controls had significantly higher FSFI scores than the RA patients across all six domains (p ≤ 0.001) and the overall score (p < 0.001). Controls had significantly higher FSFI scores than the PsA patients across four of the six domains (p ≤ 0.026) and the overall score (p = 0.008). There were no statistically significant differences between the RA and PsA groups. Patient pain, patient global status and Health Assessment Questionnaire scores were not significantly correlated with the total FSFI score in either PsA or RA. CONCLUSIONS: These findings demonstrate that decreased sexual functioning is more common in women with RA and PsA when compared with controls. All female patients with RA and PsA should be screened for sexual dysfunction. | |
31707982 | Disease activity improvements with optimal discriminatory ability between treatment arms: | 2019 Nov 10 | BACKGROUND: The ACR20 has been validated as the best discriminator of efficacy in placebo-controlled trials, but not in head-to-head trials comparing effective therapies in patients with rheumatoid arthritis (RA). We assessed the most discriminatory ACR response and most discriminatory percent improvement in disease activity measures for Simplified Disease Activity index (SDAI), Clinical Disease Activity index (CDAI), and 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)) using different patient populations and trial designs. METHODS: Data from two placebo-controlled studies in established RA and two head-to-head studies in early RA were analyzed. The numeric ACR response for each treatment and P value for the difference between treatments were calculated at multiple time points to determine the ACR response associated with the lowest P value. Similarly, values for percent improvement from baseline in SDAI, CDAI, and DAS28(CRP) with the most discrimination between treatments were examined. RESULTS: In the head-to-head early RA trials, the minimum P value and greatest treatment difference between the active comparator arms at 6 months was achieved at higher ACR rates and greater percent improvements in other disease activity measures. In established RA, lower responses (minimum P value and maximum treatment difference) and smaller improvements in disease activity scores had better discriminatory ability at 6 months. CONCLUSIONS: The most discriminatory ACR response rate and percent improvement in disease activity measures were higher in head-to-head active comparator trials in early RA versus placebo-controlled trials in established RA. This difference should be considered in future clinical trial designs. TRIAL REGISTRATION: NCT00195663, NCT00420927, NCT00195702. | |
30398030 | IL-17A haplotype confers susceptibility to systemic lupus erythematosus but not to rheumat | 2019 Mar | AIM: Recent studies highlight the importance of the interleukin (IL)-17A cytokine in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). There are also reports of associations between some single nucleotide polymorphisms (SNPs) in IL-17A and RA but not SLE. Notably, these findings have not been replicated in all studied populations. The aim of this study was to investigate whether the IL-17A -737Â T/C (rs8193036), -444A/G (rs3819024), -197G/A (rs2275913), and -121G/A (rs8193037) SNPs conferred susceptibility to SLE (or lupus nephritis) or to RA in a Mexican population. METHODS: The study included 1367 Mexican subjects, 501 with RA, 367 with SLE, and 499 healthy controls. IL-17A was genotyped using a TaqMan 5' allelic discrimination assay. RESULTS: Our results showed that the IL-17A -737Â T/C, -444A/G, -197G/A, and -121G/A SNPs had similar genotype and allele frequencies in patients with SLE (or lupus nephritis) or RA and in controls. However, an IL-17A haplotype (TAGA) showed an association with SLE susceptibility (odds ratio 2.43, PÂ =Â 0.004) but not with RA susceptibility. CONCLUSIONS: These results confirm that the IL-17A -737T/C, -444A/G, -197G/A, and -121G/A SNPs are not risk factors for RA, but the IL-17A TAGA haplotype is a risk factor for SLE. This is the first report to document an association between IL-17A and SLE susceptibility in adults. | |
31501466 | Mosaicism of XX and XXY cells accounts for high copy number of Toll like Receptor 7 and 8 | 2019 Sep 9 | The X chromosome, hemizygous in males, contains numerous genes important to immunological and hormonal function. Alterations in X-linked gene dosage are suspected to contribute to female predominance in autoimmunity. A powerful example of X-linked dosage involvement comes from the BXSB murine lupus model, where the duplication of the X-linked Toll-Like Receptor 7 (Tlr7) gene aggravates autoimmunity in male mice. Such alterations are possible in men with autoimmune diseases. Here we showed that a quarter to a third of men with rheumatoid arthritis (RA) had significantly increased copy numbers (CN) of TLR7 gene and its paralog TLR8. Patients with high CN had an upregulated pro-inflammatory JNK/p38 signaling pathway. By fluorescence in situ hybridization, we further demonstrated that the increase in X-linked genes CN was due to the presence of an extra X chromosome in some cells. Men with RA had a significant cellular mosaicism of female (46,XX) and/or Klinefelter (47,XXY) cells among male (46,XY) cells, reaching up to 1.4% in peripheral blood. Our results present a new potential trigger for RA in men and opens a new field of investigation particularly relevant for gender-biased autoimmune diseases. | |
30864557 | Studying the Association between STAT4 Gene Polymorphism and Susceptibility to Rheumatoid | 2019 Mar | BACKGROUND: STAT4 is a transcription factor that plays a role in various cytokine signaling pathways and in T cell subsets differentiation. Several studies have reported STAT4 gene polymorphism in association with various autoimmune diseases. OBJECTIVE: To evaluated the association between STAT4 rs7574865 SNP and RA risk by meta-analysis. METHODS: Two major databases, namely Scopus and PubMed, were searched to find studies investigating the STAT4 polymorphism and RA in different populations up to November 2017. Association between STAT4 polymorphism and RA were analyzed using pooled odds ratio (OR) and their corresponding 95% CI. RESULTS: In this meta-analysis, 21 population studies (16 papers) comprising 15,732 cases and 15641 healthy subjects evaluating the STAT4 gene rs7574865 SNP were included based on inclusion criteria. Herein, we found a significant positive association between minor T allele as well as different genotypes with the risk of RA. CONCLUSIONS: In summary, this study revealed an association between STAT4 gene rs7574865 SNP and risk of RA. | |
30168272 | Efficacy of abatacept tapering therapy for sustained remission in patients with rheumatoid | 2019 Jan | AIM: To investigate whether remission can be sustained for rheumatoid arthritis (RA) patients after tapering abatacept (ABT). METHOD: All patients were naïve to biological disease-modifying anti-rheumatic drugs (bDMARDs) and in low or moderate Disease Activity Score of 28 joints with C-reactive protein (DAS)28-CRP). ABT was administrated intravenously (IV) or subcutaneously (SC) for 36 weeks to patients with RA, who had not previously received bDMARDs. As the ABT tapering protocol, ABT was administrated SC at 125 mg every 2 weeks for 12 weeks in patients with remission. RA disease activity was assessed by DAS28-CRP and ultrasonography. Remission was assessed by defining it as DAS28-CRP <2.3. RESULTS: Of the 51 patients, 84.3% were women (mean age 68.7 ± 10.2 years, mean disease duration 7.7 ± 10.2 years). Twenty-nine patients achieved remission and a power Doppler (PD) score ≤1 at each joint at 36 weeks, followed by tapering ABT. Of these patients, 25 sustained DAS28-CRP remission, and DAS28-CRP was not significantly elevated (1.62 ± 0.41 to 1.69 ± 0.49) at 48 weeks, but the total PD score was significantly elevated (1.52 ± 1.21 to 2.59 ± 2.81 P = 0.049). Longer disease duration, higher DAS28-CRP at 24 weeks, and higher total PD score at 24 weeks were predictors of an elevated total PD score after tapering ABT therapy. CONCLUSION: These findings suggest that ABT tapering is a promising short-term strategy to sustain remission in patients with RA, and ultrasonography is a useful tool for monitoring disease activity after tapering ABT. | |
29166759 | Magnetic resonance imaging-assessed synovial and bone changes in hand and wrist joints of | 2019 May | BACKGROUND/AIMS: Magnetic resonance imaging (MRI) is a sensitive and useful method for the detection of synovitis and joint destruction in rheumatoid arthritis (RA) patients. However, the patterns of MRI-detected bone erosion, bone marrow edema (BME), synovitis, and tenosynovitis have received insufficient attention. Therefore, this study evaluated the patterns of bone erosion, BME, synovitis, and tenosynovitis, and calculated the RA-MRI score (RAMRIS) of patients with RA at the carpal and metacarpophalangeal (MCP) joints using MRI. METHODS: MRI datasets from 43 RA patients were analyzed. All patients had undergone MRI of one wrist. In addition, 36 patients had MCP joint images taken, and three had also received MRI of the contralateral wrist and MCP joints. The MR images were evaluated for bone erosion, BME, and synovitis in consensus by two blinded readers according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RAMRIS. The MRI-detected tenosynovitis was evaluated based on Haavardsholm's tenosynovitis score. RESULTS: The capitate, lunate, triquetrum, and hamate bones were the most common sites of erosion and BME and showed the highest RAMRIS erosion and BME scores. Moreover, MRI-detected tenosynovitis was present in 78.3% of all patients with RA, and the extensor compartment 4 and flexor digitorum profundus and superficialis were frequently affected. CONCLUSION: This study identified the distribution and prevalence of MRI-detected bone erosion, BME, synovitis, and tenosynovitis of the wrist and MCP joints in RA patients. The patterns of the MRI-detected abnormalities may help to select sites for the application of MRI protocols in clinical trials and practice. | |
31399128 | Impact of pharmacist educational intervention on disease knowledge, rehabilitation and med | 2019 Aug 9 | BACKGROUND: The objective of this study is to evaluate the effectiveness of pharmacist intervention in improving disease knowledge, adherence to treatment, health-related quality of life (HRQoL) and direct cost of treatment. The study also documents patient satisfaction with pharmacist counselling as a quality control measure. METHODS/DESIGN: This is a randomized, single-blind, two-arm, controlled trial in patients with rheumatoid arthritis visiting outpatient rheumatology clinics in Karachi, Pakistan. We will enroll patients with established diagnosis of rheumatoid arthritis over 3 months. The patients would be randomized through a computer-generated list into the control group, i.e., usual care or into the intervention group, i.e., pharmaceutical care, in a ratio of 1:1, after providing signed written consent. The study will take place in two patient-visits over the course of 3 months. Patients in the intervention group would receive intervention from the pharmacist while those in the control group will receive usual care. Primary outcomes include change in mean score from baseline (week 0) and at follow up (week 12) in disease knowledge, adherence to medications and rehabilitation/physical therapy. The secondary outcomes include change in the mean direct cost of treatment, HRQoL and patient satisfaction with pharmacist counselling. DISCUSSION: This is a novel study that evaluates the role of the pharmacist in improving treatment outcomes in patients with rheumatoid arthritis. The results of this trial could set the foundation for future delivery of care for this patient population in Pakistan. The results of this trial would be published in a peer-reviewed journal. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03827148 . Registered on February 2019. |