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ID PMID Title PublicationDate abstract
23041839 C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autor 2013 Jul INTRODUCTION: Collagen-induced arthritis (CIA) has traditionally been performed in MHC class II A(q)-expressing mice, whereas most genetically modified mice are on the C57BL/6 background (expressing the b haplotype of the major histocompatibility complex (MHC) class II region). However, C57BL/6 mice develop arthritis after immunisation with chicken-derived collagen type II (CII), but arthritis susceptibility has been variable, and the immune specificity has not been clarified. OBJECTIVE: To establish a CIA model on the C57BL/6 background with a more predictable and defined immune response to CII. RESULTS: Both chicken and rat CII were arthritogenic in C57BL/6 mice provided they were introduced with high doses of Mycobacterium tuberculosis adjuvant. However, contaminating pepsin was strongly immunogenic and was essential for arthritis development. H-2(b)-restricted T cell epitopes on chicken or rat CII could not be identified, but expression of A(q) on the C57BL/6 background induced T cell response to the CII260-270 epitope, and also prolonged the arthritis to be more chronic. CONCLUSIONS: The putative (auto)antigen and its arthritogenic determinants in C57BL/6 mice remains undisclosed, questioning the value of the model for addressing T cell-driven pathological pathways in arthritis. To circumvent this impediment, we recommend MHC class II congenic C57BL/6N.Q mice, expressing A(q), with which T cell determinants have been thoroughly characterised.
21087445 Identification of a novel cell type-specific intronic enhancer of macrophage migration inh 2011 Feb The aim of this study was to determine the genetic regulation of macrophage migration inhibitory factor (MIF). DNase I hypersensitivity was used to identify potential hypersensitive sites (HS) across the MIF gene locus. Reporter gene assays were performed in different human cell lines with constructs containing the native or mutated HS element. Following phylogenetic and transcription factor binding profiling, electrophoretic mobility shift assay (EMSA) and RNA interference were performed and the effects of incubation with mithramycin, an antibiotic that binds GC boxes, were also studied. An HS centred on the first intron of MIF was identified. The HS acted as an enhancer in human T lymphoblasts (CEMC7A), human embryonic kidney cells (HEK293T) and human monocytic cells (THP-1), but not in a fibroblast-like synoviocyte (FLS) cell line (SW982) or cultured FLS derived from rheumatoid arthritis (RA) patients. Two cis-elements within the first intron were found to be responsible for the enhancer activity. Mutation of the consensus Sp1 GC box on each cis-element abrogated enhancer activity and EMSA indicated Sp1 binding to one of the cis-elements contained in the intron. SiRNA knock-down of Sp1 alone or Sp1 and Sp3 together was incomplete and did not alter the enhancer activity. Mithramycin inhibited expression of MIF in CEMC7A cells. This effect was specific to the intronic enhancer and was not seen on the MIF promoter. These results identify a novel, cell type-specific enhancer of MIF. The enhancer appears to be driven by Sp1 or related Sp family members and is highly sensitive to inhibition via mithramycin.
22767598 Visfatin/pre-B-cell colony-enhancing factor (PBEF), a proinflammatory and cell motility-ch 2012 Aug 17 Adipokines such as adiponectin and visfatin/pre-B-cell colony-enhancing factor (PBEF) have been recently shown to contribute to synovial inflammation in rheumatoid arthritis (RA). In this study, we evaluated the pathophysiological implication of visfatin/PBEF in the molecular patterns of RA synovial tissue, focusing on RA synovial fibroblasts (RASFs), key players in RA synovium. Expression of visfatin/PBEF in synovial fluid and tissue of RA patients was detected by immunoassays and immunohistochemistry. RASFs were stimulated with different concentrations of visfatin/PBEF over varying time intervals, and changes in gene expression were evaluated at the RNA and protein levels using Affymetrix array, real-time PCR, and immunoassays. The signaling pathways involved were identified. The influence of visfatin/PBEF on fibroblast motility and migration was analyzed. In RA synovium, visfatin/PBEF was predominantly expressed in the lining layer, lymphoid aggregates, and interstitial vessels. In RASFs, visfatin/PBEF induced high amounts of chemokines such as IL-8 and MCP-1, proinflammatory cytokines such as IL-6, and matrix metalloproteinases such as MMP-3. Phosphorylation of p38 MAPK was observed after visfatin/PBEF stimulation, and inhibition of p38 MAPK showed strong reduction of visfatin-induced effects. Directed as well as general fibroblast motility was increased by visfatin/PBEF-induced factors. The results of this study indicate that visfatin/PBEF is involved in synovial fibroblast activation by triggering fibroblast motility and promoting cytokine synthesis at central sites in RA synovium.
22392695 Safety and efficacy of abatacept in eight rheumatoid arthritis patients with chronic hepat 2012 Aug OBJECTIVE: There are no previous studies on the use of abatacept in patients with chronic hepatitis B. This medical record review assessed the safety and efficacy of abatacept in 8 patients with rheumatoid arthritis (RA) and chronic hepatitis B. METHODS: A retrospective analysis of patients with RA and chronic hepatitis B treated with abatacept was conducted. The primary outcome was the 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) at each followup visit along with markers of hepatitis B reactivation, including aspartate aminotransferase, alanine aminotransferase, and hepatitis B viral load. RESULTS: A total of 47 visit data points were recorded. The mean ± SD duration of followup of patients receiving abatacept was 19.1 ± 12.7 months (range 3-33 months). Analysis was limited to 18 months of followup (included 77% of all visits [36 of 47]). Four patients were started on antiviral prophylaxis for hepatitis B with the initiation of abatacept, while 4 patients were not. Among the 4 patients who received antiviral prophylaxis, RA improved as evidenced by a statistically significant decrease in DAS28-ESR scores, and none had reactivation of hepatitis B. In the 4 patients without antiviral prophylaxis, there was no significant decrease in the DAS28-ESR scores and all 4 experienced reactivation of hepatitis B. There were no adverse events other than the hepatitis B reactivation. CONCLUSION: Use of abatacept in patients with RA and chronic hepatitis B appears feasible if antiviral prophylaxis for hepatitis B is given concurrently. In these patients there were no non-hepatitis-related adverse effects. These data are encouraging and should lead to initiation of controlled trials of abatacept in hepatitis B.
21767688 It's good to know: how treatment knowledge and belief affect the outcome of distant healin 2011 Aug OBJECTIVE: This small-scale study explores the role of expectancy in response to distant healing by testing two hypotheses: 1) Participants aware of placement in the healing condition will report greater relief than those aware they are not receiving distant healing; 2) Participants who express belief in distant healing will report greater relief than those expressing disbelief. METHODS: Sixty patients were recruited from a rheumatology outpatient clinic, and through online support networks and blogs. Participants were randomly allocated to one of four conditions, those in the healing condition received distant healing from self-reported healers, while participants in the control condition received no intervention. Half of the participants knew their treatment allocation and half were blinded. The primary outcome measures were the General Health Questionnaire (GHQ-12) and the Short-form McGill Pain Questionnaire. The Paranormal Belief Scale and a measure designed to assess belief in distant healing were given to determine if belief was correlated with healing outcomes. RESULTS: Awareness of being a recipient of distant healing appeared to be associated with improved outcomes for those in the healing group. Medium to large improvements in GHQ scores (d=.76) and McGill Pain scores (d=.45) were calculated for the groups aware of their condition. Participants unaware that they were receiving healing showed no evidence of improved outcomes. Belief in healing did not have an effect on self-reported outcomes. CONCLUSIONS: Improvements in reported pain and well-being appear to have been caused by knowledge of allocation in the distant healing condition rather than distant healing alone.
22427408 Mapping pathogenesis of arthritis through small animal models. 2012 Nov Animal models have been used for a number of decades to study arthritis and have contributed greatly to unravelling mechanisms of pathogenesis and validating new targets for treatment. All animal models have sets of limitations and over the years there has been natural refinement of existing models as well as creation of new ones. The success of genetic modification in mice has fuelled an exponential increase in the use of murine models for arthritis research and has significantly increased our understanding of disease processes. This review focuses on those rodent models of RA and OA that have current utility and are widely used by the research community. We highlight the subtle but important differences in existing models by positioning them on a pathogenesis map whereby model selection is determined by the specific aspect of disease to be studied. We discuss the evolving challenges in in vivo arthritis studies and our perceived gaps for future new model development. The document includes technical and cost implications of performing the described models, and the ethical considerations of such approaches.
21906492 Cutaneous melanoma in patients in treatment with biological therapy: review of the literat 2011 Aug 15 Herein we report a case of a melanoma arising in a patient receiving adalimumab and methotrexate for rheumatoid arthritis. A limited number of studies reported melanoma growth in patients undergoing treatment with biologics. This case report with a brief review of literature suggests that patients under treatment with biologics should be counseled to identify new pigmented lesions or changes in preexisting nevi. Clinicians' collaboration will facilitate recognition and timely diagnosis of early melanoma. If there is any doubt, excision for histological evaluation should be considered. Pending new studies, careful observation is encouraged.
21647867 Implementation of a treat-to-target strategy in very early rheumatoid arthritis: results o 2011 Oct OBJECTIVE: Clinical remission is the ultimate therapeutic goal in rheumatoid arthritis (RA). Although clinical trials have proven this to be a realistic goal, the concept of targeting at remission has not yet been implemented. The objective of this study was to develop, implement, and evaluate a treat-to-target strategy aimed at achieving remission in very early RA in daily clinical practice. METHODS: Five hundred thirty-four patients with a clinical diagnosis of very early RA were included in the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study. Treatment adjustments were based on the Disease Activity Score in 28 joints (DAS28), aiming at a DAS28 of <2.6 (methotrexate, followed by the addition of sulfasalazine, and exchange of sulfasalazine with biologic agents in case of persistent disease activity). The primary outcome was disease activity after 6 months and 12 months of followup, according to the DAS28, the European League Against Rheumatism (EULAR) response criteria, and the modified American College of Rheumatology (ACR) remission criteria. Secondary outcomes were time to first DAS28 remission and outcome of radiography. RESULTS: Six-month and 12-month followup data were available for 491 and 389 patients, respectively. At 6 months, 47.0% of patients achieved DAS28 remission, 57.6% had a good EULAR response, and 32.0% satisfied the ACR remission criteria. At 12 months, 58.1% of patients achieved DAS28 remission, 67.9% had a good EULAR response, and 46.4% achieved ACR remission. The median time to first remission was 25.3 weeks (interquartile range 13.0-52.0). The majority of patients did not have clinically relevant radiographic progression after 1 year. CONCLUSION: The successful implementation of this treat-to-target strategy aiming at remission demonstrated that achieving remission in daily clinical practice is a realistic goal.
22440825 Relationship between area-level socio-economic deprivation and autoantibody status in pati 2012 Oct OBJECTIVES: The aims of this study were to assess the association between area-level socio-economic deprivation and the phenotype of rheumatoid arthritis (RA), defined by rheumatoid factor (RF) and anticitrullinated peptide antibody (AC PA) status, and to determine whether any observed association can be explained by smoking. METHODS: The authors performed logistic regression analysis of 6298 patients with RA, defined by American College of Rheumatology classification criteria modified for genetic studies. Analysis was stratified by cohort/recruitment centre. Socio-economic deprivation was measured using the Townsend Index. RESULTS: Deprivation predicted RF but not ACPA positivity, independent of smoking. The ORs for trend across tertiles, adjusted for smoking, gender, period of birth and cohort/recruitment centre, were 1.14 (95% CI 1.01 to 1.29) for RF and 1.01 (95% CI 0.87 to 1.16) for ACPA. Even after adjusting for deprivation, smoking was strongly associated with ACPA positivity (OR 1.38, 95% CI 1.22 to 1.55). There was no evidence of any effect modification by the RA risk alleles (HLA-DRB1 shared epitope and PTPN22 rs2476601) that have previously been shown to modify the effect of smoking on ACPA and RF positivity. CONCLUSIONS: Among patients with RA, deprivation predicted RF positivity but not ACPA positivity. The effect of deprivation did not appear to be explained by smoking. Deprivation may be a marker for previously unrecognised, potentially modifiable environmental influences on the immunological phenotype of RA. Furthermore, given the known associations of RF positivity with prognosis and response to treatment in RA, these findings have potential implications for resource allocation and healthcare delivery.
21971280 New-onset psoriasis associated with adalimumab: a report of two cases. 2011 Sep 15 TNF-α inhibitors, including adalimumab, are increasingly used in the management of inflammatory cutaneous, gastrointestinal, and rheumatologic diseases. An untoward class effect of these medications is the development of new-onset psoriasis, particularly in patients treated for rheumatologic diseases without any personal or family history of cutaneous psoriasis. We report two patients that developed cutaneous and histologic changes consistent with psoriasis while receiving treatment with adalimumab for inflammatory arthridities: one patient with Crohn disease and ankylosing spondylitis who tolerated adalimumab for 15 months before developing psoriasis and another patient with rheumatoid arthritis who developed psoriasis 3 years after starting adalimumab. Both patients experienced rapid resolution of their psoriasis after discontinuation of adalimumab.
21402700 Celastrus-derived celastrol suppresses autoimmune arthritis by modulating antigen-induced 2011 Apr 29 Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and articular damage. Proinflammatory cytokines, antibodies, and matrix-degrading enzymes orchestrate the pathogenic events in autoimmune arthritis. Accordingly, these mediators of inflammation are the targets of several anti-arthritic drugs. However, the prolonged use of such drugs is associated with severe adverse reactions. This limitation has necessitated the search for less toxic natural plant products that possess anti-arthritic activity. Furthermore, it is imperative that the mechanism of action of such products be explored before they can be recommended for further preclinical testing. Using the rat adjuvant-induced arthritis model of human RA, we demonstrate that celastrol derived from Celastrus has potent anti-arthritic activity. This suppression of arthritis is mediated via modulation of the key proinflammatory cytokines (IL-17, IL-6, and IFN-γ) in response to the disease-related antigens, of the IL-6/IL-17-related transcription factor STAT3, of antibodies directed against cyclic citrullinated peptides and Bhsp65, and of the activity of matrix metalloproteinase-9 and phospho-ERK. Most of the clinical and mechanistic attributes of celastrol are similar to those of Celastrus extract. Several studies have addressed the antitumor activity of celastrol. Our study highlights the anti-arthritic activity of Celastrus-derived celastrol and the underlying mechanisms. These results provide a strong rationale for further testing and validation of the use of celastrol and the natural plant extract from Celastrus as an adjunct (with conventional drugs) or alternative modality for the treatment of RA.
23264340 Circulating maternal cytokines influence fetal growth in pregnant women with rheumatoid ar 2013 Dec BACKGROUND: High rheumatoid arthritis (RA) disease activity during pregnancy is associated with a lower birth weight. Active RA is characterised by high circulating levels of cytokines, which can mediate placental growth and remodelling. OBJECTIVES: To assess the influence of maternal serum cytokine levels on birth weight in RA pregnancy. METHODS: This study is embedded in the PARA Study, a prospective study on RA and pregnancy. In the present study, 161 pregnant women with RA and 32 healthy pregnant women were studied. The main outcome measures were birth weight SD score (birth weight SDS) in relation to maternal serum levels of interleukin-10 (IL-10), interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα) at three different time points: preconception and during the first and third trimester. Single-nucleotide polymorphisms (SNPs) in the corresponding cytokine genes were also studied. RESULTS: During the first trimester, IL-10 was detectable in 16% of patients with RA, IL-6 in 71%, and TNFα in all patients with RA. Mean birth weight SDS of children born to mothers with RA was higher when IL-10 level was high compared with low (difference=0.75; p=0.04), and lower when IL-6 was high compared with low (difference=0.50; p<0.01) in the first trimester. No correlation was seen at the other time points studied or with TNFα. Cytokine levels were not related to their corresponding SNPs. CONCLUSIONS: Maternal IL-10 and IL-6 levels are associated with fetal growth in RA. In the first trimester, high IL-10 levels are associated with higher birth weight SDS, and high IL-6 levels are associated with lower birth weight SDS, even after correction for disease activity.
20851655 Rheumatoid anemia. 2011 Mar Rheumatoid anemia is a typical example of anemia of chronic disease. It differs from other forms of anemia, such as iron deficiency anemia or iatrogenic anemia. Rheumatoid anemia is normochromic, normocytic or, less often, microcytic, aregenerative, and accompanied with thrombocytosis. Serum transferrin levels are normal or low, transferrin saturation is decreased, serum ferritin levels are normal or high, the soluble transferrin receptor (sTfR) is not increased (a distinguishing feature with iron deficiency anemia), and the sTfR/log ferritin ratio is lower than 1. This review discusses the prevalence and impact of rheumatoid anemia based on a review of the literature. Iron metabolism, absorption, diffusion, storage, and use by the bone marrow are described using published data on transferrin, ferritin, and hepcidin. Hepcidin is now recognized as a key factor in rheumatoid anemia, in conjunction with the cytokine interleukin-6 (IL-6). Hepcidin is a hormone that lowers serum iron levels and regulates iron transport across membranes, preventing iron from exiting the enterocytes, macrophages, and hepatocytes. In addition, hepcidin inhibits intestinal iron absorption and iron release from macrophages and hepatocytes. The action of hepcidin is mediated by binding to the iron exporter ferroportin. Hepcidin expression in the liver is dependent on the protein hemojuvelin. Inflammation leads to increased hepcidin production via IL-6, whereas iron deficiency and factors associated with increased erythropoiesis (hypoxia, bleeding, hemolysis, dyserythropoiesis) suppress the production of hepcidin. Data from oncology studies and the effects of recombinant human IL-6 support a causal link between IL-6 production and the development of anemia in patients with chronic disease. IL-6 diminishes the proportion of nucleated erythroid cells in the bone marrow and lowers the serum iron level, and these abnormalities can be corrected by administering an IL-6 antagonist. IL-6 stimulates hepcidin gene transcription, most notably in the hepatocytes. Studies involving human hepatocyte exposure to a panel of cytokines showed that IL-6, but not TNFα or IL-1, induced the production of hepcidin mRNA. Recent data on hepcidin level variations in patients with rheumatoid arthritis are reviewed. Rheumatoid anemia is best corrected by ensuring optimal control of systemic disease activity. The role for iron supplementation (per os or intravenously) and erythropoietin in the treatment of rheumatoid anemia is discussed. Given the cascade of interactions linking IL-6, hepcidin, and anemia, IL-6 antagonists hold considerable promise for the management of rheumatoid anemia.
20833548 Three-dimensional kinematics during deep-flexion kneeling in mobile-bearing total knee art 2011 Dec We performed an in vivo radiographic analysis of tibiofemoral and polyethylene (PE) insert motions during weight-bearing kneeling beyond 120° of flexion in one high-flexion knee arthroplasty design to determine if kinematics changed over time and if axial rotation occur between the PE insert and the tibial baseplate. Twenty knees implanted with a posterior-stabilized rotating-platform (RP) knee arthroplasty were postoperatively evaluated at 3, 6, and 12 months. The averaged flexion angles were 122°, 129°, and 131° at 3, 6, and 12 months, respectively, showing that the improvement of flexion was achieved up to 6 months. The femoral condyles translated posteriorly from extension to maximum flexion. There was a significant increase in AP translation of femoral lateral condyle in the maximum flexion kneeling between 12 months and the two other intervals (p=0.0003 at 3 months and p=0.016 at 6 months), while no differences in those of medial condyle between all intervals. Almost all rotation occurred at the surface between the tibial baseplate and the PE insert (p=0.0479 at 3 months, p=0.0008 at 6 months, and p=0.0479 at 12 months), almost no rotation occurred at the surface between the PE insert and the femoral component. There were significant increases in the amount of internal rotation angle during full flexion between the tibial component and the PE insert up to 12 months. Knees implanted with this RP knee arthroplasty design show deep-flexion knee kinematics that are consistent with the implant design intent.
22390484 Twelve years' experience with etanercept in the treatment of rheumatoid arthritis: how it 2012 Mar Etanercept is approved for the treatment of patients with moderate-to-severe active rheumatoid arthritis (RA), polyarticular juvenile RA, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis. Randomized clinical trials have shown that it improves the signs and symptoms of early and long-standing RA and other inflammatory arthritides, prevents radiographic progression and improves the patients' health-related quality of life. It is more effective when combined with methotrexate than alone. It is generally well tolerated, and seems to be relatively safe in the short term, as confirmed by clinical trials, long-term observational studies and postmarketing surveillance over 12 years' use in clinical practice. It slightly increases the risk of serious infections. The incidence of malignancies during clinical trials and postmarketing surveillance is no different from that expected in the general population, except for the greater frequency of lymphoma. However, this is closely related to current RA activity and therefore suggests that it is not directly related to the drug. This article considers the published data in terms of clinical practice and changes in the progression of RA.
23212872 Optimizing MRI for imaging peripheral arthritis. 2012 Nov MRI is increasingly used for the assessment of both inflammatory arthritis and osteoarthritis. The wide variety of MRI systems in use ranges from low-field, low-cost extremity units to whole-body high-field 7-T systems, each with different strengths for specific applications. The availability of dedicated radiofrequency phased-array coils allows the rapid acquisition of high-resolution images of one or more peripheral joints. MRI is uniquely flexible in its ability to manipulate image contrast, and individual MR sequences may be combined into protocols to sensitively visualize multiple features of arthritis including synovitis, bone marrow lesions, erosions, cartilage changes, and tendinopathy. Careful choice of the imaging parameters allows images to be generated with optimal quality while minimizing unwanted artifacts. Finally, there are many novel MRI techniques that can quantify disease levels in arthritis in tissues including synovitis and cartilage.
22573521 Drug delivery trends in clinical trials and translational medicine: growth in biologic mol 2012 Aug There are 94,709 clinical trials across 179 countries. Approximately half (47,467) are related to the three categories within the scope of the free online resource "Drug Delivery Trends in Clinical Trials and Translational Medicine," which are (1) drug delivery technology and systems, (2) biological molecule platforms, and (3) pharmacokinetic and pharmacodynamic interactions. In this commentary, trends in biological molecule platforms and their impacts are discussed. The sales of top 15 biologic drugs have reached over $63 billion in 2010. In the past 10 years, major pharmaceutical companies have acquired biological molecule platforms and have become integrated biopharmaceutical companies, highlighting the role of biotechnology in driving new therapeutic product development. The top three products--Remicade, Enbrel, and Humira--indicated for arthritis and colitis and targeted to tumor necrosis factor-alpha (TNF-α), each generated over $6 billion in annual sales. In addition to TNF-α, biologic candidates targeted to other inflammatory molecules are in clinical development, partly driven by commercial interests and medical need. Although clinical experience indicates that all the anti-TNF-α molecular platforms are effective for rheumatoid arthritis, Crohn's disease, and colitis, whether the new agents can provide additional relief or cures remains to be seen.
21279991 The risk of cancer in patients with rheumatoid arthritis: a nationwide cohort study in Tai 2011 Feb OBJECTIVE: The association of rheumatoid arthritis (RA) and malignancy has rarely been explored in Asian populations. The aim of this study was to investigate the relative risk of cancer in Taiwanese patients with RA and to identify groups of patients with a high risk of cancer. METHODS: We conducted a nationwide cohort study of the risk of cancer among 23,644 patients with RA who had no history of malignancies, using the National Health Insurance database of Taiwan from 1996 to 2007. Standardized incidence ratios (SIRs) for various cancers were analyzed. RESULTS: Among the patients with RA, 935 cancers were observed. Patients with RA had an increased risk of cancer (SIR 1.23, 95% confidence interval [95% CI] 1.22-1.23), especially hematologic cancers (SIR 2.74, 95% CI 2.68-2.81). The relative risk of cancer was higher among younger patients. Most cancer cases were detected within the first year following the diagnosis of RA. The relative risk of cancer decreased as the duration of observation increased. Among hematologic cancers, the risk of non-Hodgkin's lymphoma was greatest (SIR 3.54, 95% CI 3.45-3.63). Among solid tumors, the risk of cancers of the kidney and vagina/vulva was highest. A decreased risk of cancers of the cervix and nonmelanoma skin cancer in patients with RA was also observed. CONCLUSION: Patients with RA have an increased risk of cancer, especially hematologic and kidney cancers. The relative risk of cancer in patients with RA decreased with long-term followup. Cancer screening with continued vigilance is recommended for patients with RA.
22463799 TNF-alpha antagonism and cancer risk in rheumatoid arthritis: is continued vigilance warra 2012 Mar Rheumatoid arthritis (RA) is a chronic, systemic inflammatory arthritis that can lead to significant damage and dysfunction of involved joints. Prior to 1998, treatment options were limited to disease modifying anti-rheumatic drugs, commonly referred to as DMARDs like methotrexate, sulfasalazine, hydroxychloroquine, and gold salts. Tumor necrosis factor alpha (TNF-α) is a central cytokine that drives the inflammation in RA; hence inhibition of TNF-α offers an attractive treatment strategy in RA. The introduction of TNF-α inhibitors, a class of biologic DMARDs, has dramatically changed the treatment of RA as these are highly effective therapies. Medication-related adverse events remain a major problem in health care. This is true of the TNF-α antagonists as well, with particular concerns about increased risks of infections and malignancy. Because clinical trials performed prior to medication approval are limited by the number and clinical complexity of participants and the duration of the trials, post-marketing surveillance is critical in identifying adverse events. In order to better clarify the safety issues related to the use of TNF-α inhibitors in RA, several studies using large observational registries along with pooled meta-analyses of these studies have been published. This review will summarize the data from these recent studies on the question of malignancy risk associated with TNF-α inhibitor use in RA. It is comforting that the data from these studies do not support an increased risk of cancer, except non-melanoma skin cancer, with the use of TNF-α antagonists in adults with RA.
23062815 Alexithymia and emotional awareness in females with Painful Rheumatic Conditions. 2012 Nov OBJECTIVE: Research about the deficit of emotional regulation in Painful Rheumatic Conditions (PRC) indicates that these patients have alexithymic characteristics, as revealed by the Toronto Alexithymia Scale (TAS-20). However, the use of a unique measure to assess alexithymic trends has been questioned. The aim of the present study is twofold: to compare the levels of alexithymia and emotional awareness in females with and without PRC; and to test the predictive validity of alexithymia measures beyond negative emotions. METHOD: Thirty-nine women with PRC of diverse etiology and twenty-two healthy females responded to the TAS-20, the Levels of Emotional Awareness Scale (LEAS) and questionnaires of anxiety and depression. RESULTS: The total score, factor 1 (difficulty identifying feelings) and factor 2 (difficulty describing feelings) scores of TAS-20 were significantly higher among women with PRC than controls. Females with PRC had lower scores in the subscale "self" of the LEAS (capacity to describe their own emotional experience) than the control group. Only the LEAS significantly predicted the status group after adjusting for anxiety and depression. CONCLUSION: Our results highlighted the impairment of emotion processing in patients with PRC and the importance of using a multimodal assessment of emotional regulation in future research.