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ID PMID Title PublicationDate abstract
24757034 Socioeconomic disparities in the health of african americans with rheumatoid arthritis fro 2014 Dec OBJECTIVE: To examine cross-sectional baseline data from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis registry for the association between socioeconomic status (SES) with clinical and self-report health outcomes. METHODS: We analyzed data on 937 African Americans who provided comprehensive sociodemographic data in addition to self-reported health outcomes. SES measures included educational attainment, homeownership, household income, and occupation. Outcomes included measures of disease activity, joint damage, autoantibody status, and self-reported measures. Multivariable linear, logistic, and zero-inflated Poisson regression models were used to estimate associations of each SES measure with rheumatoid arthritis (RA) outcomes, controlling for sex, age, disease duration, comorbid conditions, body mass index, smoking, methotrexate/leflunomide use, and biologic agent use. RESULTS: The mean age was 54 years, 86% were women, and the mean RA disease duration was 7.8 years. Approximately 24% had less than a high school degree, 56% had a nonprofessional occupation, 75% had a household income ≤$30,000, and 55% were nonhomeowners. In multivariable regression models, significantly increased associations of disease activity measures and self-reported health outcomes were observed with low household income (≤$30,000/year) and nonhomeownership. Education less than high school was primarily associated with self-reported health outcomes. Among participants with disease duration <2 years, associations of SES were confined to self-reported measures. CONCLUSION: Our results indicate significant socioeconomic disparities in self-reported physical and mental health, clinical disease activity measures, and autoantibody status among African Americans with RA not explained by differences in demographics, medication use, and health behaviors.
23172750 Consensus statement on blocking the effects of interleukin-6 and in particular by interleu 2013 Apr BACKGROUND: Since approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other inflammatory diseases. This consensus document informs on interference with the IL-6 pathway based on evidence and expert opinion. METHODS: Preparation of this document involved international experts in RA treatment and RA patients. A systematic literature search was performed that focused on TCZ and other IL6-pathway inhibitors in RA and other diseases. Subsequently, incorporating available published evidence and expert opinion, the steering committee and a broader expert committee (both including RA patients) formulated the current consensus statement. RESULTS: The consensus statement covers use of TCZ as combination- or monotherapy in various RA populations and includes clinical, functional and structural aspects. The statement also addresses the second approved indication in Europe JIA and non-approved indications. Also early phase trials involving additional agents that target the IL-6 receptor or IL-6 were evaluated. Safety concerns, including haematological, hepatic and metabolic issues as well as infections, are addressed likewise. CONCLUSIONS: The consensus statement identifies points to consider when using TCZ, regarding indications, contraindications, screening, dose, comedication, response evaluation and safety. The document is aimed at supporting clinicians and informing patients, administrators and payers on opportunities and limitations of IL-6 pathway inhibition.
23335273 Suppression of hyaluronan synthesis alleviates inflammatory responses in murine arthritis 2013 May OBJECTIVE: To clarify the roles of hyaluronan (HA) in joint inflammation and the process of joint destruction, using 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, in a mouse model of collagen-induced arthritis (CIA) and in a monolayer culture of fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis. METHODS: DAB/1J mice were immunized with type II collagen. The effects of 4-MU were evaluated by the physiologic arthritis score, paw swelling, the histologic arthritis score, and expression of matrix metalloproteinase 3 (MMP-3) and MMP-13 in chondrocytes and synovial tissue. In vitro, the effect of 4-MU on messenger RNA and protein expression of MMP-1 and MMP-3 was determined. The effects of 4-MU on HA deposition and on serum/medium concentrations of HA were analyzed using biotinylated HA binding protein staining and an HA binding assay, respectively. RESULTS: Treatment with 4-MU in mice with CIA dramatically decreased the severity of arthritis (based on the arthritis score), paw thickness, and histopathologic changes. MMP-3 and MMP-13 expression in chondrocytes and synovial cells was significantly inhibited by 4-MU in vivo. Treatment with 4-MU also inhibited MMP-1 and MMP-3 expression in tumor necrosis factor α-stimulated FLS, in a dose-dependent manner. The 4-MU-induced decreases in the serum HA concentration in mice with CIA and in "medium" and "pericellular" HA concentrations in cultured FLS support the contention that the inhibitory mechanism of 4-MU is mediated by HA suppression. CONCLUSION: Reduced disease activity induced by 4-MU in mice with CIA revealed HA to be a crucial regulator in the course of arthritis. Therefore, 4-MU is a potential therapeutic agent in arthritis, and its inhibitory mechanism is possibly mediated by suppression of HA synthesis.
24515724 Bufalin, a bioactive component of the Chinese medicine chansu, inhibits inflammation and i 2014 Aug Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) contribute to the destruction of cartilage and bone by production of metalloproteinases (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM). Bufalin, a major component of Venenum Bufonis, can attenuate the invasion of various cancer cells. Here, we investigated the effects of bufalin on tumor necrosis factor-alpha (TNF-α)-induced invasion of RAFLSs. Western blot analysis and electrophoretic mobility shift assay were conducted to analyze the nuclear translocation of p65/nuclear factor-kappa B (NF-κB) and NF-κB DNA-binding activity. Semiquantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were performed to assess the expression of cytokines. Our results revealed that TNF-α significantly increased p65 translocation into nucleus (P < 0.01) and enhanced NF-κB DNA-binding activity, which were dose-dependently inhibited by bufalin. Furthermore, bufalin attenuated the TNF-α-induced interleukin-1beta (IL-1β), IL-6, and IL-8 production in RAFLSs in a concentration-dependent manner. Interestingly, TNF-α-induced invasion of RAFLSs was dampened by the pretreatment of bufalin. Additionally, bufalin decreased the mRNA abundance and secretion of MMP-9 in TNF-α-treated RAFLSs. Our results reveal that bufalin can inhibit TNF-α-induced NF-κB activation, cytokine production, invasion, and MMP-9 expression in RAFLSs, indicating a therapeutic potential of bufalin on RA.
24626168 Regulatory T-cell vaccination independent of auto-antigen. 2014 Mar 14 To date, efforts to treat autoimmune diseases have primarily focused on the disease symptoms rather than on the cause of the disease. In large part, this is attributed to not knowing the responsible auto-antigens (auto-Ags) for driving the self-reactivity coupled with the poor success of treating autoimmune diseases using oral tolerance methods. Nonetheless, if tolerogenic approaches or methods that stimulate regulatory T (Treg) cells can be devised, these could subdue autoimmune diseases. To forward such efforts, our approach with colonization factor antigen I (CFA/I) fimbriae is to establish bystander immunity to ultimately drive the development of auto-Ag-specific Treg cells. Using an attenuated Salmonella vaccine expressing CFA/I fimbriae, fimbriae-specific Treg cells were induced without compromising the vaccine's capacity to protect against travelers' diarrhea or salmonellosis. By adapting the vaccine's anti-inflammatory properties, it was found that it could also dampen experimental inflammatory diseases resembling multiple sclerosis (MS) and rheumatoid arthritis. Because of this bystander effect, disease-specific Treg cells are eventually induced to resolve disease. Interestingly, this same vaccine could elicit the required Treg cell subset for each disease. For MS-like disease, conventional CD25(+) Treg cells are stimulated, but for arthritis CD39(+) Treg cells are induced instead. This review article will examine the potential of treating autoimmune diseases without having previous knowledge of the auto-Ag using an innocuous antigen to stimulate Treg cells via the production of transforming growth factor-β and interleukin-10.
23938059 Influence of patient characteristics on perceived risks and willingness to take a proposed 2013 Aug 12 BACKGROUND: The causes of the underutilization of disease modifying anti-rheumatic drugs (DMARDS) for rheumatoid arthritis (RA) are not fully known, but may in part, relate to individual patient factors including risk perception. Our objective was to identify the determinants of risk perception (RP) in RA patients and predictors of their willingness to take a proposed DMARD (DMARD willingness). METHODS: A cross-sectional mail survey of RA patients in a community rheumatology practice. Patients were presented a hypothetical decision scenario where they were asked to consider switching DMARDs. They evaluated how risky the proposed medication was and how likely they would be to take it. RESULTS: The completed sample included 1009 RA patients. The overall survey response rate was 71%. PATIENT CHARACTERISTICS: age 61.6 years (range 18-93), 75% female, minority 6.5%, low or marginal health literacy 8.8%, depression 15.0%, duration RA 13.1 years (range 0.5 - 68). Regression models demonstrated that health literacy, independent of low educational achievement or other demographic (including race), was a common predictor of both RP and DMARD willingness. There was partial mediation of the effects of HL on DMARD willingness through RP. Depression and happiness had no significant effect on RP or DMARD willingness. RP was influenced by negative RA disease and treatment experience, while DMARD willingness was affected mainly by perceived disease control. CONCLUSIONS: Risk aversion may be the result of potentially recognizable and correctable cognitive defect. Heightened clinician awareness, formal screening for low health literacy or cognitive impairment in high-risk populations, may identify patients could benefit from additional decision support.
24092415 A weighted genetic risk score using all known susceptibility variants to estimate rheumato 2015 Jan BACKGROUND: There is currently great interest in the incorporation of genetic susceptibility loci into screening models to identify individuals at high risk of disease. Here, we present the first risk prediction model including all 46 known genetic loci associated with rheumatoid arthritis (RA). METHODS: A weighted genetic risk score (wGRS) was created using 45 RA non-human leucocyte antigen (HLA) susceptibility loci, imputed amino acids at HLA-DRB1 (11, 71 and 74), HLA-DPB1 (position 9) HLA-B (position 9) and gender. The wGRS was tested in 11 366 RA cases and 15 489 healthy controls. The risk of developing RA was estimated using logistic regression by dividing the wGRS into quintiles. The ability of the wGRS to discriminate between cases and controls was assessed by receiver operator characteristic analysis and discrimination improvement tests. RESULTS: Individuals in the highest risk group showed significantly increased odds of developing anti-cyclic citrullinated peptide-positive RA compared to the lowest risk group (OR 27.13, 95% CI 23.70 to 31.05). The wGRS was validated in an independent cohort that showed similar results (area under the curve 0.78, OR 18.00, 95% CI 13.67 to 23.71). Comparison of the full wGRS with a wGRS in which HLA amino acids were replaced by a HLA tag single-nucleotide polymorphism showed a significant loss of sensitivity and specificity. CONCLUSIONS: Our study suggests that in RA, even when using all known genetic susceptibility variants, prediction performance remains modest; while this is insufficiently accurate for general population screening, it may prove of more use in targeted studies. Our study has also highlighted the importance of including HLA variation in risk prediction models.
24074853 FOXO in the hole: leveraging GWAS for outcome and function. 2013 Sep 26 GWAS studies of autoimmune disorders have yielded hundreds of replicated associations, but moving from genetic association to functional studies with potential clinical relevance is a challenge. Leveraging GWAS data, Lee et al. now identify FOXO3 activity as predictive of disease severity in Crohn's disease and rheumatoid arthritis as well as malaria, likely by acting through regulation of cytokine production in monocytes.
25418136 Expression of choline and acetylcholine transporters in synovial tissue and cartilage of p 2015 Feb Increasing evidence is showing that the non-neuronal cholinergic system plays an important role in the pathology of rheumatoid arthritis (RA). Choline transport into the cell is the rate-limiting step for the synthesis of acetylcholine (ACh), which can be released directly or in vesicles from the cell. However, in the human joint little is known about choline import or the release of ACh from the cell. Thus, we analyze the expression of members of the organic cation transporter (OCT), of the newly discovered choline transporter-like (CTL) family and of classical neuronal components such as the high-affinity choline transporter (CHT1) and the vesicular ACh transporter (VAChT) in the synovium and cartilage of the human hip joint from patients with osteoarthritis (OA) and RA. OCT1, OCT3 and OCTN1 and all members of the CTL family were expressed in synovial and cartilage samples. The expression of CTL1 and CTL2 was localized in synovial macrophages and fibroblasts. CHT1 mRNA expression was detectable only in the synovium, whereas VAChT was completely absent in all samples. Therefore, in the human joint, choline transport into the cell and the release of ACh seems to be mediated mainly by members of the OCT and CTL family. Expression of transporters appears not to be influenced by the pathological state, as no differences have been detected between joints from OA or RA patients. Importantly, however, all necessary components for choline import and the release of non-neuronal ACh are present in the human joint.
23819334 [Genetic factors of angiogenic dysregulation in women with rheumatoid arthritis]. 2013 AIM: To study genotype distribution in the MMP and VEGF genes, angiogenesis regulators, and their combinations with genotypes in other cytokines genes with proangiogenic activity in female patients with rheumatoid arthritis (RA) and healthy individuals. SUBJECTS AND METHODS: 509 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 135 female patients aged 27-66 years with RA, were examined. TNF-alpha gene promoter single nucleotide polymorphisms (SNP) -863 C --> A, TNFA -308 G --> A, TNFA -238 G --> A; IL 1beta-31 C --> T, IL4 -590 C --> T, IL6 -174 G --> C, IL10 -1082 G --> A and IL10 -592 A --> C; VEGF -2578 C --> A, VEGF +936 C --> T; MMP 2 -1306 C --> T, MMP 9 -1562 C --> T were investigated by the restriction analysis of amplification products. RESULTS: The patients with RA show a preponderance of the combinations of genotypes in vascular endothelial growth factor (VEGF) synthesis inducers, which are related to the high-level production of this factor, and those of genotypes in the degradation of the extracellular matrix of MMP2 and MMP9, which characterize the low baseline elaboration of matrix metalloproteinases (MMP) with a high capability for their induced synthesis, which is specific to the dysregulated states of the angiogenesis control system. Along with MMP and VEGF genotypes, the combinations most commonly contain IL1beta, IL4, IL10, IL6, and TNF-alpha genotypes. CONCLUSION: The study of the pathogenesis of RA must comprehensively investigate the role of the genes of the factors involved in the regulation of angiogenesis and inflammation, with particular emphasis on molecular genetic mechanisms for monitoring the baseline level of production of these regulatory factors.
23192907 Immediate and past cumulative effects of oral glucocorticoids on the risk of acute myocard 2013 Jan OBJECTIVES: To determine the effect of glucocorticoids (GCs) on acute myocardial infarction (MI) risk in patients with RA. METHODS: Using administrative health data, we conducted a population-based cohort study of 8384 incident RA cases (1997-2006). Primary exposure was incident GC use. MI events were ascertained using hospitalization and vital statistics data. We used Cox proportional-hazards models and modelled GC use as four alternative time-dependent variables (current use, current dose, cumulative dose and cumulative duration), adjusting for demographics, comorbidities, cardiovascular drug use, propensity score and RA characteristics. Sensitivity analyses explored potential effects of unmeasured confounding. RESULTS: Within 50 238 person-years in 8384 RA cases, we identified 298 incident MI events. Multivariable models showed that current GC use was associated with 68% increased risk of MI [Hazard ratio (HR) = 1.68, 95% CI 1.14, 2.47]. Similarly, separate multivariable models showed that current daily dose (HR = 1.14, 95% CI 1.05, 1.24 per each 5 mg/day increase), cumulative duration of use (HR = 1.14, 95% CI 1.00, 1.29 per year of GC use) and total cumulative dose (HR = 1.06, 95% CI 1.02, 1.10 per gram accumulated in the past) were also associated with increased risk of MI. Furthermore, in the same multivariable model, current dose and cumulative use were independently associated with an increased risk of MI (10% per additional year on GCs and 13% per 5 mg/day increase). CONCLUSION: GCs are associated with an increased risk of MI in RA. Our results suggest a dual effect of GCs on MI risk, an immediate effect mediated through current dosage and a long-term effect of cumulative exposure.
25068763 Rituximab and tocilizumab for the treatment of rheumatoid arthritis. 2014 Jul OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of rituximab and tocilizumab compared with adalimumab, etanercept, and infliximab, in patients with rheumatoid arthritis not responding to first-line treatment, and to compare the efficacy and safety of rituximab versus tocilizumab in patients not responding to anti-tumor necrosis factor α (anti-TNF) therapy. METHODS: A literature search of randomized controlled trials, controlled clinical trials, and systematic reviews was performed to evaluate efficacy and safety of rituximab and tocilizumab. RESULTS: Twenty-four RCTs were included in this systematic review with 6,357 participants; 3,450 treated with biological DMARD and 2,907 with standard care. In patients not responding to first-line treatment, rituximab shows lower response rate in at least 50 percent improvement in the American College of Rheumatology criteria (ACR50) and ACR70 compared with etanercept, at 6 months of follow-up. Tocilizumab shows higher ACR70 response rate compared with infliximab, at the same follow-up time. Other results showed no significant differences. Indirect comparisons between rituximab and tocilizumab in patients not responding for at least one anti-TNF, shows higher ACR20 response rate for tocilizumab at 6 months of follow-up. Regarding safety, adalimumab and etanercept were associated with significant fewer withdrawals due to adverse events compared with infliximab. CONCLUSIONS: Considering efficacy, safety, and the availability of 3 anti-TNFs in the National Medicines Formulary (adalimumab, etanercept, and infliximab), it seems appropriate to remove infliximab from the coverage, and introduce tocilizumab for patients not responding for at least one anti-TNF.
24620998 Inhibitor of DNA binding 1 as a secreted angiogenic transcription factor in rheumatoid art 2014 Mar 13 INTRODUCTION: Rheumatoid arthritis (RA) is characterized by enhanced blood vessel development in joint synovium. This involves the recruitment of endothelial progenitor cells (EPCs), allowing for de novo vessel formation and pro-inflammatory cell infiltration. Inhibitor of DNA Binding 1 (Id1) is a transcription factor characteristic of EPCs that influences cell maturation. METHOD: Enzyme-linked immunosorbant assay (ELISA) and polymerase chain reaction (PCR) were used to examine Id1 levels in synovial fluid (SF) and endothelial cells (ECs), respectively. Immunohistology was used to determine the expression of Id1 in synovial tissue (ST). Human dermal microvascular EC (HMVEC) migration and tube forming assays were used to determine if recombinant human Id1 (rhuId1) and/or RA SF immunodepleted Id1 showed angiogenic activity. We also utilized the RA ST severe combined immunodeficient (SCID) mouse chimera to examine if Id1 recruits EPCs to RA synovium. RESULTS: ST samples immunostained for Id1 showed heightened expression in RA compared to osteoarthritis (OA) and normal (NL) ST. By immunofluorescence staining, we found significantly more Id1 in RA compared to OA and NL vasculature, showing that Id1 expressing cells, and therefore EPCs, are most active in vascular remodeling in the RA synovium. We also detected significantly more Id1 in RA compared to OA and other arthritis SFs by ELISA, which correlates highly with Chemokine (C-X-C motif) ligand 16 (CXCL16) levels. In vitro chemotaxis assays showed that Id1 is highly chemotactic for HMVECs and can be attenuated by inhibition of Nuclear Factor κB and phosphoinositide 3-kinase. Using in vitro Matrigel assays, we found that HMVECs form tubes in response to rhuId1 and that Id1 immunodepleted from RA SF profoundly decreases tube formation in Matrigel in vitro. PCR showed that Id1 mRNA could be up-regulated in EPCs compared to HMVECs in response to CXCL16. Finally, using the K/BxN serum induced arthritis model, we found that EC CXCR6 correlated with Id1 expression by immunohistochemistry. CONCLUSIONS: We conclude that Id1 correlates highly with CXCL16 expression, EPC recruitment, and blood vessel formation in the RA joint, and that Id1 is potently angiogenic and can be up-regulated in EPCs by CXCL16.
24580026 HLA-G +3142 polymorphism as a susceptibility marker in two rheumatoid arthritis population 2014 Apr In this study, we sought to investigate the genetic influence of two HLA-G 3'-untranslated region (3'-UTR) polymorphisms - 14 bp (rs66554220) and +3142C>G (rs1063320) and their compounding haplotypes in susceptibility to rheumatoid arthritis (RA) in a two-region Brazilian study comprising of 539 patients and 489 controls. All subjects were polymerase chain reaction (PCR) genotyped for the referred polymorphisms and logistic regression models controlling for sex, city and age were performed. Homozygozity for the +3142G allele was associated with an increased risk of RA [odds ratio (OR) = 1.45, 95% confidence interval (CI) = 1.075-1.959, P(Bonf)  = 0.030], whereas no association was observed for the 14 bp polymorphism. Haplotype comparisons between patients and controls showed a decreased frequency of the delC haplotype in patients (OR = 0.70, 95% CI = 0.521-0.946, P(Bonf)  = 0.040), which remained significant in the rheumatoid factor (RF)-positive group (OR = 0.66, 95% CI = 0.482-0.900, P(Bonf)  = 0.018), but not in the RF-negative group. These results corroborate the hypothesis of an involvement of HLA-G in the susceptibility of RA. The +3142G allele is associated with haplotype lineages that share high identity and are regarded as low producers. The presence of the G allele in homozygosis could be responsible for a low HLA-G expression profile that could favor the triggering of RA.
23885015 Effects of the selective glucocorticoid receptor modulator compound A on bone metabolism a 2013 Oct Glucocorticoids (GCs) are potent drugs to treat rheumatoid arthritis but exert adverse skeletal effects. Compound A (CpdA) is a selective GC receptor modulator with an improved risk/benefit profile in mouse models of inflammation and bone loss. Here we tested whether CpdA also exerts bone-sparing effects under proinflammatory circumstances using the collagen-induced arthritis model, a murine model of rheumatoid arthritis. CpdA decreased disease activity, paw swelling, and the paw temperature by 43%, 12%, and 7%, respectively, but was less potent than dexamethasone (DEX), which reduced these parameters by 72%, 22%, and 10%, respectively. Moreover, T cells isolated from CpdA- and DEX-treated animals were less active based on proliferation rates after challenge with type II collagen and produced smaller amounts of interferon-γ and TNF as compared with T cells from PBS-treated mice. Histological assessment of the joints confirmed the weaker potency of CpdA as compared with DEX in preventing infiltration of inflammatory cells, induction of osteoclastogenesis, and destruction of articular cartilage. Due to the lack of GC-susceptible arthritis models, we were not able to fully address the bone-sparing potential of CpdA in inflammatory conditions. Nevertheless, the bone formation marker procollagen type 1 N-terminal peptide, a surrogate marker for GC-mediated suppression of bone formation, was significantly decreased by DEX in arthritic mice but not by CpdA. Our data indicate that CpdA moderately suppresses inflammation, whereas the concurrent effects on bone remain unknown. In light of its narrow therapeutic range, CpdA may be more useful as a molecular tool for dissecting GC actions rather than a therapeutic agent.
24192039 Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthri 2013 Nov 5 Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA. DOI: http://dx.doi.org/10.7554/eLife.01202.001.
24939007 [Gender-specific differences in comorbidities of rheumatoid arthritis]. 2014 Sep BACKGROUND: Comorbidities play an important role in the course and therapy of rheumatoid arthritis (RA). Sex-specific aspects are observed with regard to prevalence and manifestation of RA-related comorbidities. AIM: A summary of current insights into sex and gender-related aspects of frequent comorbidities in RA is given. MATERIAL AND METHODS: National data were analyzed and literature findings from meta-analyses, observational studies and reviews with regard to gender and RA-associated comorbidities are presented. RESULTS: There are gender-specific differences in the prevalence of comorbidities of RA. Depression, fibromyalgia and hypothyroidism are more frequent in women than in men, whereas cardiovascular diseases and diabetes are more common in men. Osteoarthritis and osteoporosis are frequent in both sexes. CONCLUSION: Sex and gender-specific aspects should be taken into consideration in the diagnostics and treatment of RA-related comorbidities.
24156593 Metallosis of a silastic metacarpophalangeal joint arthroplasty--a case report. 2013 Metallosis is a well-documented phenomenon in hip and knee arthroplasty from metal on metal bearing joint replacements. However, few cases of metallosis of metacarpophalangeal joint replacements have been reported. We present the case of a 49-year-old lady with rheumatoid arthritis who had previously undergone MCP joint replacements over 20 years ago. The decision was taken to revise her middle MCP joint after she developed pain and ulnar drift. At revision, the joint exhibited severe metallosis presumably arising from the grommet component of the replacement. This required considerable debridement and removal of the components and revision to a new upsized implant without grommets. It is of note that there were no external signs of metallosis with full flexion of the finger and a good roll up.
25305470 Tumor necrosis factor inhibitors: clinical utility in autoimmune diseases. 2015 Feb Tumor necrosis factor (TNF) production is amplified in several autoimmune disorders. In the 1990s, it became a validated therapeutic target used for the treatment of conditions such as rheumatoid arthritis and inflammatory bowel disease. Biologic drugs targeting TNF include engineered monoclonal antibodies and fusion proteins. Currently, there are 5 Food and Drug Administration-approved TNF inhibitors (infliximab, etanercept, adalimumab, certolizumab, and golimumab), representing close to $20 billion in sales. Clinical trials remain open to test their efficacy and safety compared with one another, as well as to measure clinical outcomes in different conditions and patient populations. The industry is also eager to develop biotherapeutics that are similar but cheaper than the currently existing biologics or are safer with higher efficacy; these are the so-called "biosimilars." Clinical utility of TNF inhibitors and indications of mono- or combined therapy with immunomodulators are reviewed here. Pharmacokinetics of the TNF inhibitors is affected by routes of administration, clearance mechanisms of immunoglobulins, and immunogenicity. Finally, strategies for management of treatment efficacy and increasing evidence for monitoring of serum concentration of TNF inhibitors are discussed, assessing for the presence of the antidrug antibodies and the different analytical methods available for laboratory testing. As clinical applications of the TNF inhibitors expand, and other classes join the revolution in the treatment of chronic inflammatory disorders, therapeutic drug monitoring of biologics will become increasingly important, with the potential to dramatically improve patient care and management.
25214721 Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th 2014 Metformin is widely used to suppress certain functions of the cells found in diseases including diabetes and obesity. In this study, the effects of metformin on downregulating IL-17-producing T (Th17) cells, activating and upregulating regulatory T (Treg) cells, suppressing osteoclastogenesis, and clinically scoring collagen-induced arthritis (CIA) were investigated. To evaluate the effect of metformin on CIA, mice were orally fed with either metformin or saline as control three times a week for nine weeks. Histological analysis of the joints was performed using immunohistochemistry and Th17 cells and Treg cells of the spleen tissue were examined by confocal microscopy staining. Metformin mitigated the severity of CIA, reduced serum immunoglobulin concentrations, and reciprocally regulated Th17/Treg axis. Also, metformin treatment of normal cells cultured in Th17 conditions decreased the number of Th17 cells and increased the number of Treg cells. Metformin decreased gene expression and osteoclastogenic activity in CIA and normal mice. These results indicate that metformin had immunomodulatory actions influencing anti-inflammatory action on CIA through the inhibition of Th17 cell differentiation and the upregulation of Treg cell differentiation along with the suppression of osteoclast differentiation. Our results suggest that metformin may be a potential therapeutic for rheumatoid arthritis.