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ID PMID Title PublicationDate abstract
20209965 [Mechanism study of action on compatible using of total alkaloids of Radix Aconiti Praepar 2009 Nov OBJECTIVE: To investigate the mechanism of action on compatible using of total alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba therapy on rheumatoid arthritis in rats. METHOD: The rat models of rheumatoid arthritis of cold and dampness syndrome were treated with total alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba. Observed the contents of hypothalamic L-ENK, hypothalamic-END, plasmatic SP, serumal IgG, serumal cell factors (IL-1beta, TNF-alpha, IL-6, IL-2, IL-10) by radioimmunity method and ultrastructural change of synovial cell in electron microscope. RESULT: Total alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba could relieve arthrocele and arthralgia and elevate the contents of L-ENK, beta-END, IL-2 and degrade the contents of SP, IgG, IL-1beta, IL-6 and inhibit abnormal secretion accentuation of synovial cell like fiber. CONCLUSION: Total alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba could be used to treat rheumatoid arthritis of cold and dampness syndrome. The mechanism of action might be that the contents of center endogenous opioid peptides had increased, the synthesis and release of SP had been inhibited, the disturbance of serumal cell factor had been adjusted, and the synthesis and secretion of serum immune globulin and abnormal secretion accentuation of synovial cell had been inhibited.
20961687 The development of fibromyalgia--I: examination of rates and predictors in patients with r 2011 Feb We determined rates and predictors of future development of fibromyalgia in patients with rheumatoid arthritis (RA). After excluding patients with fibromyalgia and those with high levels of fibromyalgia symptoms (fibromyalgianess score>10) at baseline, we studied fibromyalgia development in 9739 RA patients during 42,591 patient-years of follow-up. We defined fibromyalgia using a modification of the ACR 2010 fibromyalgia criteria. We used Cox regression to predict future fibromyalgia, and examined the accuracy of predictions using Harrell's C concordance coefficient. At the last observation, 7.4% of patients satisfied criteria, although 19.8% satisfied criteria at some point during follow-up, an incidence rate of 5.3 (95% CI 5.1, 5.6) per 100 patients years, and at rates that were similar in men (7.0%) and women (8.1%). Among those satisfying criteria, during 11,363 years of follow-up from the time of first fibromyalgia diagnosis, half of follow-up time was fibromyalgia+and was associated with markedly abnormal RA variable and FM variable scores. Demographic factors were weak predictors of fibromyalgia (C=0.604). Demographic plus RA variables (C=0.720) and demographic plus fibromyalgia variables (C=0.765), and all predictors (C=0.782) increased accuracy. Clinically important hazard ratios were noted for cognition, depression, comorbidity, and high levels of RA and FM continuous variables Overall, study results indicate that multiple, inter-correlated factors that include social disadvantage, psychological distress, comorbidity, RA severity, and fibromyalgia variables predict future development of fibromyalgia, but there is little evidence of the effect of underlying causes. After diagnosis, patients move in both directions across the diagnostic criteria cut points.
19238083 Association of physical inactivity with increased cardiovascular risk in patients with rhe 2009 Apr OBJECTIVE: Patients with rheumatoid arthritis (RA) are characterized by reduced physical activity and increased morbidity and mortality from cardiovascular disease (CVD). The aim of this study was to investigate associations between levels of physical activity and CVD risk profile in RA patients. METHODS: Levels of physical activity were assessed in 65 RA patients (43 females). Using the International Physical Activity Questionnaire, patients were allocated into three groups: active, moderately active and inactive. Anthropometric characteristics, RA activity/severity, multiple classical and novel CVD risk factors and 10-year CVD event probability were assessed and compared among the three groups. RESULTS: Significant differences were detected among groups in systolic blood pressure (P=0.006), cholesterol (P<0.001), low-density lipoprotein (P=0.01), homeostasis model assessment (P=0.001), type-I plasminogen activator inhibitor antigen (P<0.001), tissue-type plasminogen activator antigen (P=0.019), homocysteine (P=0.027), fibrinogen (P=0.001), apolipoprotein B (P=0.002) and von Willebrand Factor (P=0.001), with a consistent deterioration from the physically active to the physically inactive group. Multivariate analysis of variance revealed that levels of physical activity were significantly associated with the differences in all of the above variables (P<0.05) after adjustment for age, weight, sex, smoking status, as well as RA disease activity and severity. CONCLUSION: This cross-sectional study suggests that physically inactive RA patients have significantly worse CVD risk profile compared with physically active patients. The possible beneficial impact of increased physical activity, including structured exercise, to the CVD risk of RA patients needs to be accurately assessed in prospective studies.
19347944 Low level light effects on inflammatory cytokine production by rheumatoid arthritis synovi 2009 Apr BACKGROUND AND OBJECTIVE: Low level light therapy (LLLT) is being evaluated for treating chronic and acute pain associated with rheumatoid arthritis (RA) and other inflammatory diseases. The mechanisms underlying the effectiveness of LLLT for pain relief in RA are not clear. The objectives of this study were to determine whether LLLT decreased production of pro-inflammatory cytokines by cells from RA joints, and, if so, to identify cellular mechanisms. STUDY DESIGN/MATERIALS AND METHODS: Synoviocytes from RA patients were treated with 810 nm radiation before or after addition of tumor necrosis factor-alpha (TNF-alpha). mRNA for TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-8 was measured after 30, 60, and 180 minutes using RT-PCR. Intracellular and extracellular protein levels for 12 cytokines/chemokines were measured at 4, 8, and 24 hours using multiplexed ELISA. NF-kappaB activation was detected using Western blotting to follow degradation of IkappaBalpha and nuclear localization of the p65 subunit of NF-kappaB. RESULTS: Radiation at 810 nm (5 J/cm(2)) given before or after TNF-alpha decreases the mRNA level of TNF-alpha and IL-1beta in RA synoviocytes. This treatment using 25 J/cm(2) also decreases the intracellular levels of TNF-alpha, IL-1beta, and IL-8 protein but did not affect the levels of seven other cytokines/chemokines. TNF-alpha-induced activation of NF-kappaB is not altered by 810 nm radiation using 25 J/cm(2). CONCLUSIONS: The mechanism for relieving joint pain in RA by LLLT may involve reducing the level of pro-inflammatory cytokines/chemokines produced by synoviocytes. This mechanism may be more general and underlie the beneficial effects of LLLT on other inflammatory conditions.
19443463 CARD8 p.C10X polymorphism is associated with inflammatory activity in early rheumatoid art 2010 Apr OBJECTIVES: CARD8 and NLRP3 are constituents of the inflammasome which regulates interleukin 1beta production. The influence of polymorphisms in CARD8 and NLRP3 on rheumatoid arthritis (RA) susceptibility and severity were evaluated. METHODS: CARD8 p.C10X and NLRP3 p.Q705K genotypes were assessed in >500 controls and patients with early RA from northern Sweden. The patients were monitored regularly over a 2-year period. The 28-joint disease activity score (DAS28) and its separate components were compared across genotypes. RESULTS: Patients with one or more variant alleles in CARD8 (CARD8-X) had increased DAS28, tender joint count and erythrocyte sedimentation rate during the 2-year follow-up period despite receiving disease-modifying antirheumatic drugs to a greater extent. CARD8-X was significantly over-represented among patients who received anti-tumour necrosis factor therapy during the first 2 years. CARD8 and NLRP3 genotypes did not influence radiological joint damage and were not associated with an increased susceptibility. CONCLUSIONS: Carriage of CARD8-X is associated with a worse disease course in early RA.
21088724 Active-learning assignments to integrate basic science and clinical course material. 2010 Sep 10 OBJECTIVE: To develop, implement, and evaluate active-learning exercises requiring the integration and application of pathophysiology, medicinal chemistry, pharmacology, and therapeutics knowledge of osteoarthritis and rheumatoid arthritis to formulate therapeutic recommendations for patients with musculoskeletal disorders. DESIGN: Two team-based case study exercises, one evaluating a patient with osteoarthritis and the second, a patient with rheumatoid arthritis, were developed, incorporating material and questions from pathophysiology, medicinal chemistry, pharmacology, and therapeutics. The learning assignments were implemented in a required pharmacotherapy module. ASSESSMENT: Student learning was evaluated using performance on the team-based case study exercises and on 2 examinations. A standard student course evaluation was used to assess students' impressions of the learning activity. The mean student grades for the osteoarthritis and rheumatoid arthritis activities were 9.1 and 8.9, respectively, on a 10-point scale. The majority of students indicated that the learning exercises were more than adequate to excellent in helping students learn. CONCLUSION: The addition of active-learning activities was successful in teaching pharmacy students the knowledge needed to formulate therapeutic recommendations for patients with musculoskeletal disorders.
20097590 Creutzfeldt-Jakob disease in a patient treated by etanercept for rheumatoid arthritis (RA) 2010 Mar We describe a patient in whom sporadic Creutzfeldt-Jakob disease (sCJD) occurred one year after the onset of etanercept therapy for rheumatoid arthritis (RA). This association could be a chance occurrence. However, TNF-alpha has been implicated in the pathogenesis of neurodegeneration in sCJD and etanercept might worsen the disease. Such an aggravation has been observed in multiple sclerosis, in which TNF-alpha is the key mediator of demyelination. It may be of interest studying the impact of treatment with TNF-alpha antagonists on prevalence and incidence of those neurodegenerative diseases involving TNF-alpha mediation, such as Alzheimer disease.
20009112 Transcript profiling towards personalised medicine in rheumatoid arthritis. 2009 Dec Rheumatoid arthritis (RA ) is a chronic inflammatory joint disease that is heterogeneous in nature. The heterogeneity is reflected by the variation in responsiveness to virtually any treatment modality. Since our understanding of the molecular complexity is incomplete and criteria for categorisation are limited, we mainly consider the disease RA as group average. A powerful way to gain insight into the complexity of RA has arisen from DNA microarray technology, which allows an open-ended survey to comprehensively identify the genes and biological pathways that are associated with clinically defined conditions. During the last decade encouraging results have been generated towards the molecular description of complex diseases in general. Here, I describe developments in genomics research that provide a framework to increase our understanding of the pathogenesis and the identification of biomarkers for early diagnosis, prognosis and stratification, aimed at a personal medicine approach in RA .
19483089 Can rheumatoid arthritis responsiveness to methotrexate and biologics be predicted? 2009 Sep This review briefly recapitulates the existing markers predictive of RA responsiveness to treatment, focusing on MTX alone or combined with a biologic. In addition to the demographic and clinical factors, an update is provided of the predictive biomarkers identified by large-scale gene and protein analyses that generated new insights into the ability of high-throughput analysis of biological systems to select new potential indicators. Among the large-scale analysis tools now available, pharmacogenetics and pharmacogenomics (including transcriptomic and proteomic approaches) have been shown to provide such new putative biomarkers of therapeutic responses.
20537320 Autologous stromal vascular fraction cells: a tool for facilitating tolerance in rheumatic 2010 Since the days of Medawar, the goal of therapeutic tolerogenesis has been a "Holy Grail" for immunologists. While knowledge of cellular and molecular mechanisms of this process has been increasing at an exponential rate, clinical progress has been minimal. To provide a mechanistic background of tolerogenesis, we overview common processes in the naturally occurring examples of: pregnancy, cancer, oral tolerance and anterior chamber associated immune deviation. The case is made that an easily accessible byproduct of plastic surgery, the adipose stromal vascular fraction, contains elements directly capable of promoting tolerogenesis such as T regulatory cells and inhibitory macrophages. The high content of mesenchymal and hematopoietic stem cells from this source provides the possibility of trophic/regenerative potential, which would augment tolerogenic processes by decreasing ongoing inflammation. We discuss the application of this autologous cell source in the context of rheumatoid arthritis, concluding with some practical examples of its applications.
20077124 Differences between the United States and the United Kingdom in the treatment of rheumatoi 2010 Apr Previous studies have found differences in rheumatoid hand surgical practice around the world. The specific aim of this study is to compare baseline characteristics of rheumatoid arthritis (RA) patients in the United States (US) and the United Kingdom (UK) that may be influenced by the two different health-care systems. Patients were recruited from three sites (two in the US and one in England) as part of a National Institutes of Health funded study to examine outcomes of silicone metacarpophalangeal joint (MCPJ) arthroplasty in RA patients. Outcomes measurements included biomechanical assessments (grip strength, pinch strength, and mean ulnar drift and extensor lag at the MCPJs of all four fingers), a health-related quality of life questionnaire (the Michigan Hand Outcomes Questionnaire), and a medication assessment. American patients have a significantly higher income level (p<0.001) and have completed higher levels of education (p<0.001) than British patients. There were no significant differences in terms of self-reported disease severity or deformity at the MCPJs. RA patients in the US are more likely to take biologic medications (p<0.001), steroids (p=0.02), and Cox-2 inhibitors (p=0.02). Patients in the UK are significantly more likely (p<0.001) to take nonsteroidal anti-inflammatory drugs. There are differences in the demographic characteristics and medication use of RA patients with hand deformities in the US and UK. These differences may be influenced by the private versus socialized health-care systems. However, the perception of hand disease severity in participants in this study appears to be comparable between these countries.
20485222 Factors explaining limitations in activities and restrictions in participation in rheumato 2010 Jun AIM: The objectives of this study were to examine which factors, according to the International Classification of Functioning, Disability and Health (ICF) framework contribute to the explanation of activity limitations measured by the Health Assessment Questionnaire (HAQ - model I) and which factors contribute to the explanation of participation restrictions measured by the Social Function Scale of SF-36 (model II) in patients with rheumatoid arthritis (RA). METHODS: Cross-sectional data collection of variables concerning the health status of 239 consecutively included patients with RA at the outpatient Departments of Physical Medicine and Rehabilitation of the University Hospital of Zurich and of the University Hospital of Munich was conducted. Measures included: disease activity score (DAS-28), Rheumatoid Arthritis Disease Activity Index (RADAI), HAQ, Short-form-36 (SF-36), Sociodemo-graphy Questionnaire, Comorbidity Questionnaire (SCQ), Muscle Strength Index (MSI), range of motion (EPM-ROM), grip strength, Sequentional Occupational and Dexterity Assessment (SODA), radiologic score (Ratingen Score). Multivariate regression analyses were conducted building models of explanation. RESULTS: Model I included vitality, RADAI, DAS, SODA PAIN Score, MSI and EPM-ROM as explaining variables with a globally explained variance of 53%. Model II included vitality, mental health, the HAQ and living alone as explaining variables with a globally explained variance of 42.4%. CONCLUSION: Activity limitations in RA were mainly explained by vitality and disease activity factors. Restrictions in participation in RA were mainly explained by vitality and mental health.
20298552 Slit3 inhibits Robo3-induced invasion of synovial fibroblasts in rheumatoid arthritis. 2010 INTRODUCTION: The repellent factor family of Slit molecules has been described to have repulsive function in the developing nervous system on growing axons expressing the Robo receptors. However, until today no data are available on whether these repellent factors are involved in the regulation of synovial fibroblast (SF) activity in rheumatoid arthritis (RA). METHODS: mRNA expression in primary synovial fibroblasts was quantified by quantitative reverse transcription PCR and protein expression was measured by fluorescence activated cell sorting (FACS) analysis. Different functional assays were performed with rheumatoid arthritis synovial fibroblasts (RASF): proliferation, migration and a novel in-vitro cartilage destruction assay. RESULTS: First, we found increased expression of Robo3 expression in RASF compared to normal SF. Interestingly, analysis of data from a recently published genome-wide association study suggests a contribution of ROBO3 gene polymorphisms to susceptibility of RA. Functional assays performed with RASF revealed induction of migration and cartilage destruction by Robo3 and increased matrix metalloproteinase (MMP)1 and MMP3 expression. Treatment of RASF in early passages with Slit3 led to inhibition of migration whereas RASF in later passages, having reduced Robo3 expression in cell culture, were not inhibited by Slit3 treatment. Here, reduction of Robo3 expression from passage 3 to 10 might reflect an important step in losing repulsive activity of Slit3. CONCLUSIONS: Taken together, our data showed that deregulation of the Robo3 receptor in synovial fibroblasts in RA correlates with aggressiveness of the fibroblasts. Slit3 reduces the migratory activity of synovial cells from patients with RA, potentially by repulsion of the cells in analogy to the neuronal system. Further studies will be necessary to prove Slit activity in vivo.
19854716 New insights into the experience of fatigue among patients with rheumatoid arthritis: a qu 2010 May OBJECTIVES: Patients with rheumatoid arthritis (RA) commonly experience fatigue. The aim of this study was to gain further insight into the experience of fatigue in RA. METHODS: Participants were 31 outpatients with RA of Medical Spectrum Twente, Enschede, The Netherlands, with all levels of fatigue. In-depth structured interviews on the patients' experience of fatigue were conducted and analysed using a bottom-up coding scheme, meaning that answers of patients were summarised and categorised. RESULTS: Patients' mean fatigue severity score was 50 (visual analogue scale (VAS); theoretical range 0-100). Interviews showed interindividual differences in the experience and impact of fatigue. Different patterns in emotions, consequences and management of fatigue were found. Especially younger women with multiple daily roles seemed to be vulnerable to the negative impact of RA fatigue. Patients also reported positive aspects of fatigue. Moreover, varying forms of fatigue were described. CONCLUSIONS: Results point to the existence of differences in fatigue experience according to gender, age and daily roles. This finding indicates a need for targeting advice and interventions to the individual situation of a patient. Furthermore, the positive aspects patients reported about their fatigue could facilitate an approach that is focused on remaining opportunities and not just on restrictions.
20542146 How early is the atherosclerotic risk in rheumatoid arthritis? 2010 Aug Rheumatoid arthritis is a systemic disease characterized by a reduced life expectancy mainly due to cardiovascular disease. In long-standing disease, it has been widely demonstrated that both traditional cardiovascular risk factors than chronic inflammation and immune-mediated mechanisms play a relevant role in atherosclerosis. Recently, it has been shown that the increased cardiovascular risk appears to precede rheumatoid arthritis onset and that particular immune and inflammatory factors, predating disease presentation, in association with a well-defined genetic background, may be associated with increased risk of accelerated atherosclerosis in patients with early disease. However, the effect of early immunosuppressive treatment on cardiovascular disease outcome remains uncertain. A multidisciplinary cardiovascular risk management is required to provide the better care of patients with RA at disease onset.
20863447 Persistence on therapy is a major determinant of patient-, physician- and laboratory- repo 2010 Sep OBJECTIVES: To evaluate impact of persistence on therapy on sustained major patient-, physician- and laboratory-reported outcomes (PROs, PHYROs and LAROs, respectively) in 112 recent-onset rheumatoid arthritis (RA) patients. METHODS: At each visit a rheumatologist interviewed patients regarding therapy, morning stiffness and fatigue, scored the 28-joint disease activity score and a visual analogue scale (VAS) and determined acute-phase-reactants. The patients completed the Hispanic version of the Rheumatoid Arthritis Disease Activity Index, the Medical Outcome Short Form 36 (SF-36), the Health Assessment Questionnaire (HAQ), a pain-VAS and an overall-disease activity-VAS. Persistence was defined by self-report through directed interview. Sustained major PROs, PHYROs and LAROs were defined according to cut-offs, when maintained for ≥6 months and until last follow-up. Descriptive statistics, Kaplan-Meier curves and Cox models were used. RESULTS: Total person-time of receiving therapy was of 375.5 patient-years. From February 2004 to June 2009, 36 (32.1%) patients were persistent. Baseline PROs/PHYROs/LAROs showed active disease and poor health status in both groups, but persistent patients (PP) had significantly lower HAQ (p=0.03) and overall-disease activity-VAS (p=0.01). More PP reached a sustained major SF-36-physical function-score (p=0.02). Persistence was the greatest independent risk factor for sustained major PROs (but absence of fatigue) and PHYROs, (p≤0.04). Time from baseline to major and sustained PROs (excluded absence of fatigue), PHYROs and C-reactive protein were shorter in PP (p≤0.04). CONCLUSIONS: Persistence was a strong predictor for major and sustained outcomes in early RA. Favourable outcomes appear earlier in persistent than in non-persistent patients.
20952465 Cytokines and regulatory T cells in rheumatoid arthritis and their relationship with respo 2010 Dec OBJECTIVE: To analyze circulating cytokines and regulatory T cells (Treg) in patients with rheumatoid arthritis (RA) of different durations, and their association with functional interleukin 10 (IL-10) and tumor necrosis factor-α (TNF-α) genotypes in patients treated with corticosteroids. METHODS: Serum levels of IL-6, IL-10, IL-17, IL-18, TNF-α, and transforming growth factor-ß (TGF-ß) were quantified in 196 patients and 61 healthy controls. Percentage of CD4+CD25high cells was determined by flow cytometry and Foxp3 expression by real-time reverse-transcription polymerase chain reaction. Data were related to clinical measurements and presence of the genotype -1082GG IL-10/-308GG TNF-α, previously associated with good response to corticosteroids. RESULTS: Levels of TNF-α, IL-6, and IL-18 were significantly higher in patients compared to controls, while TGF-ß and IL-10 were lower. Serum samples of patients at disease onset (n = 32) had increased IL-6 and decreased TGF-ß, but there were no differences in other cytokines. These patients also presented a higher percentage of CD4+CD25high cells than those with established disease, although no significant differences were detected in Foxp3. Patients under corticosteroid treatment who were carriers of the good responder genotype had higher levels of TGF-ß, Foxp3, and Treg compared to patients with other genotypes, while relatively lower levels of TNF-α and IL-17 were observed. CONCLUSION: Patients at onset of RA present fewer alterations in cytokine levels and Treg than those with longer disease duration, supporting the role of disease progression in subsequent changes. The antiinflammatory balance observed in high IL-10/low TNF-α patients treated with prednisone supports the use of these genetic polymorphisms as predictors of response to corticosteroid therapy.
20680496 MR imaging of atlantoaxial joint in early rheumatoid arthritis. 2010 Oct PURPOSE: This study was done to assess the involvement of the atlantoaxial joint in patients with early rheumatoid arthritis and evaluate the role of magnetic resonance (MR) imaging in depicting this early joint involvement. MATERIALS AND METHODS: Twenty patients (16 women and four men, mean age 55.0±12.9 years) with clinical and laboratory evidence of early rheumatoid arthritis (mean disease duration <12 months) were included in our study. MR imaging of the atlantoaxial joint was performed in all patients within 3 months from diagnosis. The MR features were correlated with clinical and biochemical variables. RESULTS: Five (25.0%) of the 20 patients exhibited enhancement of the periodontoid synovial spaces after gadolinium administration due to inflammatory synovitis. Compared with patients without cervical involvement, these five patients showed significantly higher values of erythrocyte sedimentation rate [median 77.0 mm/h (range 25th and 75th percentile 69.0-86.0) vs median 33.0 mm/h (range 25th and 75th percentile: 9.2-52) (p=0.007)]; significantly higher C-reactive protein values [median 53.6 mg/l (range 25th and 75th percentile 21.9-81.9) vs median 14.0 mg/l (range 25th and 75th percentile 0.8-20) (p=0.03)]; higher disease activity score [median 4.2 (range 25th and 75th percentile 3.9-5.4) vs median 3.2 (range 25th and 75th percentile 2.8-3.8) (p=0.03)]. Four (80%) of these five patients presented anti-citrulline antibodies (anti-CCP) and rheumatoid factor at laboratory testing. The latter was positive in 12 of the 20 patients (66%), and anti-CCP were positive in 15 (83%). CONCLUSIONS: MR imaging showed an atlantoaxial inflammatory synovitis in 25% of patients with early rheumatoid arthritis. Our results indicate that patients with higher disease activity are likely to be at higher risk of presenting early involvement of the atlantoaxial joint. MR imaging of the cervical spine is an excellent tool for assessing the early manifestations of rheumatoid arthritis before any destructive changes occur. Therefore, MR imaging should be included in the diagnostic workup in order to provide reliable guidance for treatment choices.
19266254 A case of lung tuberculosis in a patient with rheumatoid arthritis treated with infliximab 2009 We report a case of a 65-year-old man with rheumatoid arthritis. The patient was treated with methotrexate and prednisolone, but the disease activity remained high. A tuberculin skin test was positive. After antituberculosis (TB) chemoprophylaxis with isoniazid for four weeks, infliximab was administered. Chemoprophylaxis was continued for nine months. Active lung TB was diagnosed at 17 months after the cessation of isoniazid, namely at 27 months after starting infliximab treatment. This case report shows that TB can manifest after chemoprophylaxis in patients treated with antitumor necrosis factor agents.
20074278 Cytokines as targets for anti-inflammatory agents. 2009 Dec Well over a decade ago a central role of tumor necrosis factor (TNF) was first described in patients with rheumatoid arthritis (RA) when remarkable clinical benefit was demonstrated in patients with refractory disease were treated with using either a monoclonal antibody or a soluble receptor fusion protein. There are now five anti-TNF agents approved by regulatory agencies for treating RA. Identifying which RA patients will have a meaningful clinical response (improvement in outcomes measures such as ACR 20, DAS score, remission, etc.) when used as monotherapy, or in combination with other immunosuppressive agents remains a major research effort. Also, attention has focused on the potential adverse events that can be seen with these therapies; an increase in opportunistic infections being the most clearly linked adverse event. These anti-TNF therapies have revolutionized the clinicians' ability to make a significant impact in RA, a disease that has significant excess morbidity and mortality.