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ID PMID Title PublicationDate abstract
27112146 Increased extracellular water measured by bioimpedance and by increased serum levels of at 2017 May The aim of the study is to investigate water compartments in patients with rheumatoid arthritis (RA). Acute inflammatory episodes such as infection stimulate water retention, chiefly implemented by the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. This is an important compensatory mechanism due to expected water loss (sweating etc.). Since SNS and HPA axis are activated in RA, inflammation might be accompanied by water retention. Using bioimpedance analysis, body composition was investigated in 429 controls and 156 treatment-naïve RA patients between January 2008 and December 2014. A group of 34 RA patients was tested before and after 10 days of intensified therapy. Levels of pro-atrial natriuretic peptide (proANP) and expression of atrial natriuretic peptide in synovial tissue were investigated in 15 controls and 14 RA patients. Extracellular water was higher in RA patients than controls (mean ± SEM: 49.5 ± 0.3 vs. 36.7 ± 0.1, % of total body water, p < 0.0001). Plasma levels of proANP were higher in RA than controls. RA patients expressed ANP in synovial tissue, but synovial fluid levels and synovial tissue superfusate levels were much lower than plasma levels indicating systemic origin. Systolic/diastolic blood pressure was higher in RA patients than controls. Extracellular water levels did not change in RA patients despite 10 days of intensified treatment. This study demonstrates signs of intravascular overload in RA patients. Short-term intensification of anti-inflammatory therapy induced no change of a longer-lasting imprinting of water retention indicating the requirement of additional treatment. The study can direct attention to the area of volume overload.
26927559 [RANKL increases on peripheral blood T lymphocytes and serum Dickkopf1 decreases in rheuma 2016 Mar OBJECTIVE: To explore the roles of bone metabolism-related molecules in bone metabolic disturbance and disease progression of patients with rheumatoid arthritis (RA). METHODS: A total of 66 RA patients and 20 healthy controls were included, and their relevant clinical information was gathered. Electrochemiluminescence immunoassay (ECLIA) was used to detect the levels of osteocalcin N-terminal middle (OC-N-MID) and C-terminal cross-linked telopeptides of type 1 collagen (CTX) in serum. The serum levels of Wnt inhibitory factor Dickkopf1 (DKK1) and receptor activator of nuclear factor-κB ligand (RANKL) were determined by magnetic luminex assays. Flow cytometry was used to detect the RANKL level on peripheral blood T cells. RESULTS: Compared with healthy controls, the levels of OC-N-MID and CTX in the sera of the RA patients showed no significant difference. Level of RANKL in the sera of the RA patients was higher than that in the controls, while level of DKK1 was lower. The level of RANKL on peripheral blood T cells increased in the RA patients, especially on CD3(+) T cells. CONCLUSION: In RA patients, level of RANKL on T cells is elevated, and the serum level of RANKL increases, but DKK1 decreases.
25385260 A randomized, double-blind, placebo-controlled, twelve-week, dose-ranging study of decerno 2015 Feb OBJECTIVE: To assess the efficacy and safety of oral decernotinib (VX-509; Vertex Pharmaceuticals) monotherapy in a 12-week, randomized, double-blind, placebo-controlled, dose-ranging study of patients with rheumatoid arthritis (RA). METHODS: Two hundred four adults with active RA who had been unsuccessfully treated with ≥1 disease-modifying antirheumatic drug were administered placebo tablets or decernotinib twice a day at dosages of 25 mg, 50 mg, 100 mg, or 150 mg. Primary measures of efficacy at week 12 were the response rate according to the American College of Rheumatology 20% improvement criteria (ACR20) and mean change from baseline in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). RESULTS: At week 12, the ACR20 response rates were 39.0%, 61.0%, 65.0%, and 65.9% in the 25-mg, 50-mg, 100-mg, and 150-mg groups, respectively, and were significantly higher in the 50-mg group (P = 0.007) and the 100-mg and 150-mg groups (P = 0.002) as compared to the response rates in the placebo group (29.3%). The mean change from baseline in DAS28-CRP was greater in the 50-mg, 100-mg, and 150-mg groups as compared to the placebo group (P < 0.001). Decernotinib treatment resulted in higher ACR50 and ACR70 response rates, more patients with DAS28-CRP scores <2.6, and improvements in the Health Assessment Questionnaire disability index as compared to placebo. The most common adverse events in any decernotinib group were nausea (6.1%), headache (4.3%), an increase in levels of alanine aminotransferase (4.3%), and hypercholesterolemia (3.7%). In the groups receiving decernotinib, there was an increased risk of infections and increased liver transaminase levels. CONCLUSION: Decernotinib was efficacious in improving clinical signs and symptoms of RA at week 12 at dosages of 50-150 mg twice a day. Infections and increases in liver transaminase and lipid levels were noted as potential safety signals.
25892196 Shared epitope-antagonistic ligands: a new therapeutic strategy in mice with erosive arthr 2015 May OBJECTIVE: The mechanisms underlying bone damage in rheumatoid arthritis (RA) are incompletely understood. We recently identified the shared epitope (SE), an HLA-DRB1-coded 5-amino acid sequence motif carried by the majority of RA patients as a signal transduction ligand that interacts with cell surface calreticulin and accelerates osteoclast (OC)-mediated bone damage in collagen-induced arthritis (CIA). Given the role of the SE/calreticulin pathway in arthritis-associated bone damage, we sought to determine the therapeutic targetability of calreticulin. METHODS: A library of backbone-cyclized peptidomimetic compounds, all carrying an identical core DKCLA sequence, was synthesized. The ability of these compounds to inhibit SE-activated signaling and OC differentiation was tested in vitro. The effect on disease severity and OC-mediated bone damage was studied by weekly intraperitoneal administration of the compounds to DBA/1 mice with CIA. RESULTS: Two members of the peptidomimetics library were found to have SE-antagonistic effects and antiosteoclast differentiation effects at picomolar concentrations in vitro. The lead mimetic compound, designated HS(4-4)c Trp, potently ameliorated arthritis and bone damage in vivo when administered in picogram doses to mice with CIA. Another mimetic analog, designated HS(3-4)c Trp, was found to lack activity, both in vitro and in vivo. The differential activity of the 2 analogs depended on minor differences in their respective ring sizes and correlated with distinctive geometry when computationally docked to the SE binding site on calreticulin. CONCLUSION: These findings identify calreticulin as a novel therapeutic target in erosive arthritis and provide sound rationale and early structure/activity relationships for future drug design.
25315704 Association between the functional ITGAM rs1143679 G/A polymorphism and systemic lupus ery 2015 May The aim of this study was to determine whether the functional integrin-α-M (ITGAM) rs1143679 polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE), lupus nephritis (LN), and rheumatoid arthritis (RA). A series of meta-analyses were conducted to test for associations between the ITGAM rs1143679 polymorphism and SLE, LN, or RA. A total of 24 comparisons involving 7,738 patients and 8,309 controls for SLE, and 2,663 patients and 2,694 controls in RA were considered. Meta-analysis showed a significant association between the ITGAM rs1143679 A allele and SLE in all subjects (OR 1.773, 95 % CI 1.656, 1.901, p < 1.0 × 10(-9)). After stratification by ethnicity, the A allele was found to be significantly associated with SLE in European, Latin American, and Asian. A significant association was also found between the ITGAM A allele and lupus nephritis in Europeans (OR 2.131, 95 % CI 1.565, 2.903, p = 1.6 × 10(-7)). However, no association was found between RA and the ITGAM rs1143679 polymorphism. Our meta-analyses confirm that the ITGAM rs1143679 polymorphism is associated with SLE susceptibility in different ethnic groups and demonstrate that the polymorphism is associated with LN in European.
27185957 Disease-modifying anti-rheumatic drugs and non-melanoma skin cancer in inflammatory arthri 2016 Sep OBJECTIVES: The aim was to determine the non-melanoma skin cancer (NMSC) risk in patients with RA or PsA exposed to MTX and other DMARDs. METHODS: Information on medication was collected on 405 patients with RA or PsA in two private rheumatology practices and was matched to comprehensive histologically confirmed cancer registry data for the years 1978-2005. Relative risks (RRs) were estimated by logarithmic binomial modelling, and standardized incidence ratios (SIRs) were calculated from year-, sex- and age-specific rates of NMSC for the local population. RESULTS: Compared with no MTX usage, any MTX usage was associated with a higher rate of at least one histopathologically confirmed NMSC (SIR 4.64, 95% CI: 0.67, 33.2). The SIR was 4.81 (95% CI: 3.60, 6.29) for those receiving a cumulative dose >8000 mg compared with SIR 2.31 (95% CI: 1.58, 2.36) for <5000 mg. An increased risk was shown for both basal cell carcinomas and squamous cell carcinomas, with an apparent dose-response relationship for basal cell carcinomas but not for squamous cell carcinomas. There was an increased risk of NMSC in patients taking CSA (RR = 2.51, 95% CI: 1.23, 5.13) and D-Pen (RR 3.49, 95% CI: 1.34, 4.63) in addition to MTX, but not for patients taking AZA or LEF. CONCLUSION: MTX, and concurrent MTX and CSA or D-Pen use, is associated with an increased risk of NMSC. These results should encourage greater clinical vigilance for NMSC in treated patients with RA and PsA.
27744395 Rheumatoid Arthritis and Coronary Artery Disease: Genetic Analyses Do Not Support a Causal 2017 Jan OBJECTIVE: Inflammatory diseases, specifically rheumatoid arthritis (RA), are assumed to increase the risk of coronary artery disease (CAD). More recently, multiple single-nucleotide polymorphisms (SNP) associated with RA risk were identified. If causal mechanisms affecting risks of RA and CAD are overlapping, risk alleles for RA might also increase the risk of CAD. METHODS: Sixty-one SNP associating with RA in genome-wide significant analyses were tested for association with CAD in CARDIoGRAM (Coronary ARtery DIsease Genome wide Replication and Meta-analysis), a metaanalysis including genome-wide association data (22,233 CAD cases, 64,762 controls). In parallel, a set of SNP being associated with low-density lipoprotein cholesterol (LDL-C) was tested as a positive control. RESULTS: Twenty-nine RA-associated SNP displayed a directionality-consistent association with CAD (OR range 1.002-1.073), whereas 32 RA-associated SNP were not associated with CAD (OR range 0.96-0.99 per RA risk-increasing allele). The proportion (48%) of directionality-consistent associated SNP equaled the proportion expected by chance (50%, p = 0.09). Of only 5 RA-associated SNP showing p values for CAD < 0.05, 4 loci (C5orf30, IL-6R, PTPN22, and RAD51B) showed directionality-consistent effects on CAD, and 1 (rs10774624, locus SH2B3) reached study-wide significance (p = 7.29E-06). By contrast, and as a proof of concept, 46 (74%) out of 62 LDL-C-associated SNP displayed a directionality-consistent association with CAD, a proportion that was significantly different from 50% (p = 5.9E-05). CONCLUSION: We found no evidence that RA-associated SNP as a group are associated with CAD. Even though we were not able to study potential effects of all genetic variants individually, shared nongenetic factors may more plausibly explain the observed coincidence of the 2 conditions.
29932627 Effects and safety of Sinomenine in treatment of rheumatoid arthritis contrast to methotre 2016 Oct OBJECTIVE: To systematically evaluate the curative clinical efficacy and safety of sinomenine (SIN) in treatment of rheumatoid arthritis (RA) in comparison to methotrexate (MTX). METHODS: We searched the China National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, China Science and Technology Journal Database, Wanfang Database, Pubmed and Cochrane Library electronically up to August 31, 2015, without language limitation. Only randomized controlled trials (RCTs) were included. Software Review Manager 5.3 was used for Meta-analysis. RESULTS: A total of 16 eligible studies within 1500 RA patients were included. The meta-analysis indicated that on basis of MTX, SIN was more effective in total effective rate (P < 0.000 01). Besides, SIN alone versus MTX also showed advantages in RA therapy (P = 0.04) Taken together, adverse events occurred less frequently in combination of SIN and MTX than MTX alone (P < 0.0001), especially in digestive system (P < 0.000 01),while occurred more in dermato mucosal system with SIN treatment versus MTX (P = 0.02), and were similar for both remedies in nervous system (P = 0.12) and hematological system (P = 0.25). CONCLUTION: Compared to MTX, SIN had better clinical efficacy and relatively fewer adverse events in treatment of RA, especially when it was used together with MTX. Due to the poor methodological quality, well-designed, multiple-center RCTs are still required to further confirm the findings.
25595725 Systematic review of the presentation of coagulation factor VIII inhibitors in rheumatic d 2015 Jun OBJECTIVES: To provide a comprehensive review regarding the clinical presentation of acquired factor VIII (FVIII) inhibitors, also known as "acquired hemophilia," in patients with rheumatic diseases. METHODS: A systematic MEDLINE search was conducted to identify English-language articles published from 1993 through January 10, 2012, providing details regarding the clinical presentation, laboratory evaluation, and management of a patient(s) with newly or previously diagnosed autoimmune disease coexistent with an acquired FVIII inhibitor. RESULTS: In total, 49 patients fulfilled the criteria for inclusion in the review; the greatest percentage (24.5%) had systemic lupus erythematosus, followed by rheumatoid arthritis (16%). The majority (78%) presented with spontaneous mucocutaneous or muscular bleeding. Prolonged activated partial thromboplastin time (aPTT) was identified in all of the 45 patients for whom results were provided. Five patients presented with an asymptomatic prolonged aPTT, which was attributed to a lupus anticoagulant in two patients, only one of whom actually had a coexisting lupus anticoagulant. Invasive procedures led to serious bleeding in both of these patients, one of whom died as a result. The majority (59%) of patients experienced complete or partial remission of their inhibitors, most (96%) after systemic eradicative therapy. A total of three (6%) patients died as a direct result of FVIII inhibitors. CONCLUSIONS: Although acquired FVIII inhibitors are rare in patients with autoimmune diseases, prompt diagnosis is essential to avoid extensive bleeding, which could be life threatening. Treatment requires eradication of the factor inhibitors. Rheumatologists must be able to distinguish acquired FVIII inhibitors from lupus anticoagulants.
26247485 Tumor necrosis factor-alpha gene promoter methylation in Japanese adults with chronic peri 2016 Jun BACKGROUND AND OBJECTIVE: Over-expression of tumor necrosis factor-alpha (TNF-α) plays a pathological role in chronic periodontitis (CP) and rheumatoid arthritis (RA), which might be regulated by the epigenetic mechanism. The aim of the present study was to evaluate whether there is a unique methylation profile of the TNF-α gene promoter in blood cells of individuals with CP and RA. MATERIAL AND METHODS: The study participants consisted of 30 Japanese adults with RA (RA group), 30 race-matched adults with CP only (CP group) and 30 race-matched healthy controls (H group). Genomic DNA isolated from peripheral blood was modified by sodium bisulfite and analyzed, by direct sequencing, to investigate DNA methylation of the TNF-α gene promoter region. The level of TNF-α produced in mononuclear cells stimulated with Porphyromonas gingivalis lipopolysaccharide was determined using ELISA. RESULTS: Twelve cytosine-guanine dinucleotide (CpG) motifs were identified in the TNF-α promoter fragment from -343 to +57 bp. The CP group showed a significantly higher methylation rate and frequency at -72 bp than the H group (p < 0.01). The RA group exhibited significantly higher methylation rates at seven CpG motifs (-302, -163, -119, -72, -49, -38 and +10 bp), and significantly higher methylation frequencies at six CpG motifs (-163, -119, -72, -49, -38 and +10 bp), than the H group (p < 0.01 for all comparisons). The levels of TNF-α produced were significantly different between individuals with and without methylation at -163 bp (p = 0.03). CONCLUSION: These results suggest that the hypermethylated status of CpG motifs in the TNF-α gene promoter in blood cells may be unique to Japanese adults with CP and RA.
26903194 IL-1 receptor antagonist (IL-1Ra)-Fc ameliorate autoimmune arthritis by regulation of the 2016 Apr INTRODUCTION: IL-1β signalling has a critical role in the pathogenesis of various types of inflammatory arthritis including rheumatoid arthritis (RA). We aimed to investigate the therapeutic effects of human IL-1 receptor antagonist with Fc fragment (hIL-1Ra-Fc) on autoimmune arthritis and to identify the possible mechanisms by which hIL-1RA-Fc exerts anti-arthritic effects in a murine model of RA and patients with rheumatoid arthritis. METHODS: Collagen-induced arthritis (CIA) murine model was established in DBA/1J mice. The levels of various cytokines were determined by using enzyme-linked immunosorbent assay. The mouse joints were assessed for clinical arthritis score and histologic features. Th17 cells and Treg cells were stained by using antibodies specific for CD4, IL-17, CD25, and FoxP3. Osteoclastogenesis was determined by TRAP staining and real-time PCR. RESULTS: hIL-1RA-Fc reduced the arthritis incidence, histological inflammation and cartilage score in the CIA model. The expression of proinflammatory cytokines, VEGF and RANK, was reduced in the affected joint of hIL-1Ra-Fc-treated mice. hIL-1Ra-Fc-treated mice showed decreased number of Th17 cells with increased number of Treg cells in spleens. hIL-1Ra-Fc reduced Th17 cell differentiation by inactivation of STAT3 signalling, and reciprocally induced Treg cell differentiation through STAT5 signalling. In addition, the expression of IL-17, TNF-α, RANKL, and VEGF was decreased, while Foxp3 gene expression was increased in PBMCs of RA patients after administration of hIL-1Ra-Fc. CONCLUSION: The anti-arthritis effects of hIL-1RA-Fc are associated with regulation of balance between Th17 cells and Treg cells and suppression of osteoclastogenesis and angiogenesis in the affected joints.
26536775 [Factors Affecting Non-Specific Reaction in Latex Agglutination Turbidimetric Immunoassay 2015 Apr PURPOSE: Measurement of matrix metalloproteinase-3(MMP-3), a marker for rheumatoid arthritis, by means of latex agglutination turbidimetric immunoassay (LTIA), has come to replace ELISA kit, but pre-improvement LTIA kit S(Sekisui Medical) frequently shows false values resulting from non-specific reactions. We analyzed factors influencing the frequency of non-specific reactions for MMP-3 detection using various methods. METHOD: Serum MMP-3 levels were measured in 1,214 routine samples or 57 panels with various immunoserological abnormalities by means of pre-improvement and improved kit S, LTIA kit E (Eiken Chemical) and ELISA kit. Non-specific reaction samples were selected either from the routine samples based on the results of correlativity tests between the kits and of dilution linearity tests, or from 57 panels with immunoserological abnormalities based on the results of recovery tests. To explore the factors causing non- specific reactions, titers of rheumatoid factor (RF), immunoglobulins and four heterophil antibodies were measured in these samples. In addition, changes in findings as a result of reduction treatment or IgM absorption were examined in selected samples to clarify the effect of heterophil antibodies. RESULTS: Samples which showed suspected false values probably due to non-specific reaction numbered 75, 15, 5 and 17 as measured with pre-improvement kit S, improved kit S, kit E and ELISA kit, respectively. Kit S also showed high rate of deviation in recovery tests on panels with immunoserological abnormalities. Rate of RF titer in samples with non-specific reactions was higher than that of other factors. Non-specific reaction could be inhibited in two samples as a result of reduction treatment or absorption of IgM subtype. CONCLUSION: Pre-improvement kit S showed a higher rate of non-specific reactions than other kits. The most common cause of non-specific reactions is thought to be high RF titer, but high levels of IgM, including heterophil antibodies, may also affect the values of MMP-3.
24712864 Structure-based drug design of RN486, a potent and selective Bruton's tyrosine kinase (BTK 2015 Jan 8 Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) ( J. Pharmacol. Exp. Ther. 2012 , 341 , 90 ), which was selected for advanced preclinical characterization based on its favorable properties.
26121327 Centenarian Rates and Life Expectancy Related to the Death Rates of Multiple Sclerosis, As 2016 Feb The autoimmune diseases are among the 10 leading causes of death for women and the number two cause of chronic illness in America as well as a predisposing factor for cardiovascular diseases and cancer. Patients of some autoimmune diseases have shown a shorter life span and are a model of accelerated immunosenescence. Conversely, centenarians are used as a model of successful aging and have shown several immune parameters that are better preserved and lower levels of autoantibodies. The study reported here focused on clarifying the connection between longevity and some autoimmune and allergic diseases in 29 developed Organisation for Economic Co-operation and Development (OECD) countries, because multidisciplinary analyses of the accelerated or delayed aging data could show a distinct relationship pattern, help to identify common factors, and determine new important factors that contribute to longevity and healthy aging. The relationships between the mortality rates data of multiple sclerosis (MS), rheumatoid arthritis (RA), asthma, the incidence of type 1 diabetes (T1D) from one side and centenarian rates (two sets) as well as life expectancy data from the other side were assessed using regression models and Pearson correlation coefficients. The data obtained correspond to an inverse linear correlation with different degrees of linearity. This is the first observation of a clear tendency of diminishing centenarian rates or life expectancy in countries having higher death rates of asthma, MS, and RA and a higher incidence of T1D in children. The conclusion is that most probably there are common mechanistic pathways and factors affecting the above diseases and at the same time but in the opposite direction the processes of longevity. Further study, comparing genetic data, mechanistic pathways, and other factors connected to autoimmune diseases with those of longevity could clarify the processes involved, so as to promote longevity and limit the expansion of those diseases in the younger and older population.
26238666 Thirty-day complications in rheumatoid patients following total knee arthroplasty. 2016 Mar Although total knee arthroplasty (TKA) is highly successful for patients with end-stage rheumatoid arthritis (RA), the risks and complications associated with surgery in this cohort are less defined. The objectives of our study were to analyze the demographic and perioperative factors of RA patients that may affect post-TKA outcomes, as well as to assess the 30-day complication rates compared to osteoarthritis patients. We retrospectively evaluated the National Surgical Quality Improvement Program (NSQIP) database from 2006 to 2012 to assess all patients who underwent a primary TKA and had a diagnosis of rheumatoid arthritis (n = 141) or primary knee osteoarthritis (n = 7125). We evaluated and compared the demographic factors, social factors, preoperative factors, operative factors, and postoperative complications. The RA cohort had a lower mean age and body mass index than patients in the OA group. There was also a significantly higher incidence of women and Hispanics in the RA cohort. There was a lower incidence of diabetes and hypertension requiring medication in the rheumatoid cohort, but also a higher incidence of bleeding disorders. The RA cohort had an increased proportion of patients requiring blood transfusions and had a longer mean length of stay. The incidence of pneumonia and postoperative bleeding that required transfusion was also higher in RA patients. Rheumatoid patients had higher rates of wound infections, pulmonary embolisms, and deep vein thrombosis; however, these findings were not significant. Although RA patients with end-stage knee arthritis may benefit from TKA, these patients should be preoperatively optimized to minimize complication risks.
26936262 Inadequate response or intolerability to oral methotrexate: Is it optimal to switch to sub 2016 May Methotrexate (MTX) is considered an anchor drug in the treatment of rheumatoid arthritis. It is also the first-line therapy in a multitude of rheumatologic conditions. Low-dose oral MTX is the preliminary modality of treatment for rheumatoid arthritis due to its affordability, favorable outcomes, and limited risks. However, patients refractory to low-dose MTX therapy may require larger doses of oral MTX. Several studies in the past have demonstrated variability in bioavailability of oral MTX at high doses. This warrants a subsequent switch to parenteral MTX. Widely used among the parenteral preparations of MTX is subcutaneous (SC) MTX. SC MTX provides dependable efficacy, predictable bioavailability, sustained clinical outcomes, and minimal GI adverse effects. It is useful either singularly or in combination therapy regimens. Although SC MTX and intramuscular MTX have similar pharmacokinetics, SC MTX may be preferred by most patients. Development of prefilled syringes and auto-injectors have enabled self-administration of the medication providing the patients with a sense of independence and improved general well-being. Hence, SC MTX can prove to be more efficacious in patients refractory to oral MTX therapy or in patients experiencing severe gastrointestinal adverse effects.
26648280 Translation, cultural adaptation and reproducibility of the Oxford Shoulder Score question 2016 Jan CONTEXT AND OBJECTIVE Although shoulder questionnaires validated for Brazil do exist, none of them are aimed at populations with rheumatic disease. We believe that the Oxford Shoulder Score (OSS) may be useful in this population. The objective of this study was to translate the OSS, adapt it to Brazilian culture and test its reproducibility. DESIGN AND SETTING Validation study conducted in university outpatient clinics. METHODS The OSS was translated into Portuguese by two English teachers and was then retranslated into English by two native English teachers. These translations were reviewed by a committee to establish the version of OSS-Brazil to be administered to 30 patients with rheumatoid arthritis (RA) and shoulder pain, in order to test the cultural adaptation. The validity and reproducibility was tested among another 30 patients with RA and shoulder pain, of both genders and aged 18 to 65 years. The internal consistency and reproducibility were analyzed. The following instruments were evaluated: OSS-Brazil; a numerical scale for shoulder pain; DASH; HAQ and SF-36. RESULTS The internal consistency was 0.957 and the intra and inter-rater reproducibility was 0.917 and 0.861, respectively. A high level of correlation was found between OSS-Brazil and the following: HAQ (-0.663), DASH (-0.731) and the SF-36 domains of functional capacity (0.589), physical aspects (0.507), pain (0.624), general state of health (0.444), vitality (0.634) and mental health (0.578). CONCLUSION OSS-Brazil was successfully translated and adapted, and this version exhibited good internal consistency, reliability and construct validity.
25604867 Peripheral blood CD4(+)CD25(+)CD127(low) regulatory T cells are significantly increased by 2015 Jan 21 INTRODUCTION: Tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, is clinically effective against rheumatoid arthritis (RA), and several reports have indicated how TCZ influences a number of mechanisms underlying RA pathogenesis. However, it is still unclear whether TCZ affects inflammatory cells in peripheral blood and whether any such changes are associated with clinical response. We evaluated associations between proportions of subsets of peripheral immune cells and clinical response in patients with RA treated with TCZ. METHODS: Thirty-nine consecutive patients with RA who started to receive TCZ as their first biologic between March 2010 and April 2012 were enrolled. The proportions of several subsets of peripheral cells with their levels of expression of differentiation markers, activation markers and costimulatory molecules were measured sequentially from baseline to week 52 by flow cytometry analysis. RESULTS: Clinical Disease Activity Index (CDAI) remission was achieved in 53.8% of patients at week 52 of TCZ therapy. The proportions of CD4(+)CD25(+)CD127(low) regulatory T cells (Treg) and HLA-DR(+) activated Treg cells significantly increased with TCZ therapy (P < 0.001 and P < 0.001, respectively), whereas proportions of CD3(+)CD4(+)CXCR3(-)CCR6(+)CD161(+) T helper 17 cells did not change over the 52 weeks. The proportions of CD20(+)CD27(+) memory B cells, HLA-DR(+)CD14(+) and CD69(+)CD14(+) activated monocytes, and CD16(+)CD14(+) monocytes significantly decreased (P < 0.001, P < 0.001, P < 0.001 and P < 0.001, respectively). Among them, only the change in Treg cells was inversely correlated with the change in CDAI score (ρ = -0.40, P = 0.011). The most dynamic increase in Treg cells was observed in the CDAI remission group (P < 0.001). CONCLUSION: This study demonstrates that TCZ affected proportions of circulating immune cells in patients with RA. The proportion of Treg cells among CD4(+) cells correlated well with clinical response.
27974925 New pharmacological strategies in rheumatic diseases. 2016 Jul Targeting the pathogenic pathway of chronic inflammation represents an unmet challenge for controlling disease activity, preventing functional disability, and maintaining an adequate quality of life in patients with rheumatic diseases. Abatacept, a novel molecule that inhibits co-stimulation signal, induces an inhibitory effect on the T-cells. This will further interfere with the activity of several cell lines, leading to the normalization of the immune response. In the latest years, abatacept has been extensively investigated in studies of rheumatoid arthritis for which it was recently approved as a second line biologic treatment in Romania. This review presents the clinical efficacy of abatacept in several rheumatic diseases and highlights the safety profile of this biological agent. Abbreviations: ACR = American College of Rheumatology, ADR = Adverse drug reaction, APC = antigen presenting cell, ApS = psoriatic arthritis, CRP = C reactive protein, CTLA-4 = Cytotoxic T-Cell Lymphocyte Antigen-4, DAS = Disease activity score, DMARDs = Disease modifying antirheumatic drugs, EMA = European Medicine Agency, EULAR = European League Against Rheumatism, FDA = Food and Drugs Administration, HBV = Hepatitis B virus, JIA = Juvenile Idiopathic Arthritis, LDA = low disease activity (LDA), MRI = magnetic resonance imaging (MRI), MTX = methotrexate, RA = rheumatoid arthritis, RCT = randomized controlled trial, SS = Sjogren's syndrome, TCR = T cell receptor.
26358841 Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid art 2016 OBJECTIVES: This phase II, dose-ranging, double-blind, placebo-controlled, randomized study (NCT01463059) evaluated efficacy and safety of olokizumab (OKZ), a humanized anti-interleukin 6 monoclonal antibody, in Asian patients with moderately-to-severely active rheumatoid arthritis (RA) who had previously failed anti-TNF therapy. METHODS: Patients were randomized to one of six treatment arms: placebo or OKZ (60 mg/120 mg/240 mg every four weeks [Q4W]; or 60 mg/120 mg every two weeks [Q2W]); stratified by country and number of prior anti-TNFs. Primary efficacy variable was Week 12 change from baseline (CFB) in DAS28 CRP for 4-week cumulative dose groups of OKZ and placebo; secondary efficacy variables were Week 12 ACR20/ACR50/ACR70 response rates. Patients continued MTX treatment from baseline, without additional csDMARDs. RESULTS: Of 119 randomized patients, 88.2% completed the study. Greater improvements in DAS28(CRP) mean CFB at Week 12 were observed in all OKZ 4-week cumulative dose groups (60 mg/120 mg/240 mg) versus placebo (p < 0.0001). Week 12 ACR20/ACR50 response rates were higher in all OKZ cumulative dose groups versus PBO (p < 0.05). Incidences of adverse events were similar across OKZ 4-week cumulative dose groups (76.9-84.4%) and placebo (82.8%) with no deaths. CONCLUSIONS: OKZ demonstrated improvements in efficacy variables versus placebo in Asian patients with moderately-to-severely active RA who had previously failed anti-TNF therapy. The safety profile was as expected for this class of drug.