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ID PMID Title PublicationDate abstract
23091653 Effect of preexisting musculoskeletal diseases on the 1-year incidence of fall-related inj 2012 Sep OBJECTIVES: People who have chronic diseases, as well as gait imbalance or psychiatric drug use, may be susceptible to injuries from falls and slips. The purpose of this study was to evaluate the effect of musculoskeletal diseases on incidental fall-related injuries among adults in Korea. METHODS: We analyzed data from the 4th Korea National Health and Nutrition Examination Survey (2007-2009), which are national data obtained by a rolling survey sampling method. The 1-year incidence of fall-related injuries was defined by health service utilization within the last year due to injury occurring after a slip and fall, and musculoskeletal diseases included osteoarthritis, rheumatoid arthritis, osteoporosis, and back pain. To evaluate the effects of preexisting musculoskeletal diseases, adults diagnosed before the last year were considered the exposed group, and adults who had never been diagnosed were the unexposed group. RESULTS: The weighted lifetime prevalence of musculoskeletal disease was 32 540 per 100 000 persons. Musculoskeletal diseases were associated with a higher risk of fall-related injury after adjustment for sex, age, residence, household income, education, occupation, visual disturbance, paralysis due to stroke, and medication for depression (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.03 to 1.93). As the number of comorbid musculoskeletal diseases increased, the risk of fall-induced injuries increased (p-value for trend <0.001). In particular, patients who had any musculoskeletal condition were at much higher risk of recurrent fall-related injuries (OR, 6.20; 95% CI, 1.06 to 36.08). CONCLUSIONS: One must take into account the risk of fall-related injuries and provide prevention strategies among adults who have musculoskeletal diseases.
21193128 Complication and revision rates following total elbow arthroplasty. 2011 Jan PURPOSE: To determine the complication rates after total elbow arthroplasty (TEA) in a large and diverse patient population. METHODS: We identified patients undergoing TEA as inpatients in the years 1995 to 2005 using California's Discharge Database. Short-term outcomes of interest included rates of infection or wound complications, revision, reoperation, and pulmonary embolism that were diagnosed during an inpatient hospital admission and mortality within 90 days of index surgery. Longer-term outcomes analyzed included rates of revision, amputation, and conversion to fusion. We used regression models to estimate the role of patient and provider characteristics in predicting the rates of adverse outcomes. RESULTS: We identified 1,625 patients undergoing TEA. Early complications, defined as those requiring inpatient re-admission within the first 90 days after index surgery, were identified in 170 patients, and 132 patients required reoperation. Eighty one patients required revision in 90 days, and 48 underwent revision within one year. Early infections and wound complications requiring readmission occurred in 88 patients. In the 90 days after surgery, 4 patients had a pulmonary embolism and 10 patients died. One-hundred and twenty-one patients required revision, amputation, or fusion during the observation period, with a mean follow-up of 4 years. Hospital volume was not associated with increased risk of adverse outcomes. CONCLUSIONS: We analyzed a large and diverse patient population undergoing TEA. The overall rate of short-term complications requiring inpatient treatment was high, at over 10% (170 patients), with almost 8% (132 patients) requiring reoperation within the first 90 days. Although population-based studies have shortcomings, they can add to the body of knowledge of less frequent procedures such as TEA. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
23073266 Treat-to-target: rationale and strategies. 2012 Jul Treatment to a target level of a variable known to be associated with bad disease outcome is a concept that has been applied for many years in several specialties. In rheumatology this has not been the case, primarily because of the complexity of measures assessing disease activity of RA and insufficient knowledge of optimal strategies. Meanhwile, however, our insights into the devastating role of active disease have expanded. In parallel, the use of composite measures of disease activity to control patients tightly and adapt therapy accordingly has provided the evidence that treating RA to a target value of low disease activity or remission conveys significant benefit. The background of the treat-to-target concept and future aspects are discussed.
21081527 Increased cartilage turnover and circulating autoantibodies in different subsets before th 2011 Mar BACKGROUND: Previous studies have indicated that autoantibodies may be detected years before the clinical onset of rheumatoid arthritis (RA). Cartilage biomarkers, such as cartilage oligomeric matrix protein (COMP), have not been studied previously in samples collected before the diagnosis of RA. METHODS: Between 1991 and 1996, 30 447 subjects were included in the Malmö Diet Cancer Study (MDCS). People who developed RA after inclusion were identified by linking the MDCS database to different Swedish registers. One matched control for each validated case was selected from the MDCS. IgG antibodies against cyclic citrullinated peptide (anti-CCP) and mutated citrullinated vimentin (anti-MCV) and IgM rheumatoid factor (IgM RF) were determined by ELISA. Serum COMP was measured with a sandwich ELISA. RESULTS: 172 incident cases of RA (median time from inclusion to diagnosis 5 years; range 1-13) were identified. Pre-RA cases were significantly more likely than controls to be positive for anti-CCP (21.9% vs 0.6%), anti-MCV (29.6% vs 3.0%) and IgM RF (18.9% vs 2.4%) (all p<0.001). Overall, mean serum COMP levels did not differ between cases and controls. Among pre-RA cases included 1-3 years before diagnosis, raised COMP (>12 U/l) was seen in a greater proportion of anti-CCP-negative than anti-CCP-positive subjects (50% vs 15%; p=0.04). CONCLUSIONS: Increased cartilage turnover, measured by COMP, and circulating RA-specific antibodies may be distinct processes in the preclinical phase of RA.
20890983 Macrophage activation and coronary atherosclerosis in systemic lupus erythematosus and rhe 2011 Apr OBJECTIVE: Activation of macrophages may contribute to increased atherosclerosis and coronary artery disease in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Neopterin, a pteridine derivative, is a novel marker of monocyte and macrophage activation that is associated with atherosclerosis and cardiovascular risk in the general population. We examined the hypothesis that macrophage activation is associated with accelerated atherosclerosis in SLE and RA. METHODS: We compared serum neopterin concentrations, adjusted for age, race, sex, and serum creatinine concentration, in patients with SLE (n=148) or RA (n=166) and control subjects (n=177). In patients with SLE or RA, serum neopterin concentrations were then tested for association (adjusted for age, race, sex, serum creatinine, and medication use) with measures of disease activity or damage, inflammatory markers and mediators, and coronary artery calcium measured by electron beam computed tomography. RESULTS: Neopterin concentrations were significantly higher in patients with SLE (median 8.0, interquartile range [IQR] 6.5-9.8 nmoles/liter) and RA (median 6.7, IQR 5.3-8.9 nmoles/liter) than controls (median 5.7, IQR 4.8-7.1 nmoles/liter), and were higher in SLE patients than in RA patients (all P<0.001). In SLE, neopterin was significantly correlated with higher erythrocyte sedimentation rate (ESR; P=0.001), tumor necrosis factor α (P<0.001), monocyte chemoattractant protein 1 (P=0.005), and homocysteine concentrations (P=0.01), but in RA, it was only associated with ESR (P=0.01). Neopterin was not associated with coronary calcium in either SLE (P=0.65) or RA (P=0.21). CONCLUSION: Macrophage activation, reflected by increased serum neopterin concentrations, was increased in both SLE and RA. Neopterin was more robustly associated with atherogenic mediators of inflammation and homocysteine in SLE than in RA, but was not associated with coronary atherosclerosis in either disease.
21190991 How I treat LGL leukemia. 2011 Mar 10 Large granular lymphocyte (LGL) leukemia is characterized by a clonal expansion of either CD3(+) cytotoxic T or CD3(-) NK cells. Prominent clinical features of T-LGL leukemia include neutropenia, anemia and rheumatoid arthritis (RA). The terminal effector memory phenotype (CD3(+)/CD45RA(+)/CD62L(-)CD57(+)) of T-LGL suggests a pivotal chronic antigen-driven immune response. LGL survival is then promoted by platelet-derived growth factor and interleukin-15, resulting in global dysregulation of apoptosis and resistance to normal pathways of activation-induced cell death. These pathogenic features explain why treatment of T-LGL leukemia is based on immunosuppressive therapy. The majority of these patients eventually need treatment because of severe or symptomatic neutropenia, anemia, or RA. No standard therapy has been established because of the absence of large prospective trials. The authors use low-dose methotrexate initially for T-LGL leukemia patients with neutropenia and/or RA. We recommend either methotrexate or oral cyclophosphamide as initial therapy for anemia. If treatment is not successful, patients are switched to either the other agent or cyclosporine. The majority of patients experience an indolent clinical course. Deaths infrequently occur because of infections related to severe neutropenia. As there are no curative therapeutic modalities for T-LGL leukemia, new treatment options are needed.
22418389 T-cell receptor signaling and the pathogenesis of autoimmune arthritis: insights from mous 2012 Mar The immune system has evolved to survey and respond appropriately to the universe of foreign pathogens, while at the same time deploying an intricate repertoire of mechanisms that keep responses to host tissues in check. For the adaptive immune system, specificity and sensitivity are provided by a large repertoire of antigen T-cell receptors (TCRs) constructed in their extracellular domain to recognize antigenic peptide fragments restricted and presented by histocompatibility complex molecules, and coupled through intracellular domains to signal transduction modules that serve to transmit environmental cues inside the cell. In this review we consider recent evidence that has provided insight into how altered TCR signaling thresholds could contribute to human autoimmune arthritis, including rheumatoid arthritis (RA), and the spondyloarthropathies (SpA). We also discuss mechanistic studies that demonstrate how perturbations of T-cell antigen receptor signaling in the SKG mouse model can promote systemic autoimmunity and the intersection with essential innate immune pathways that lead to the development of chronic inflammatory phenotypes.
22210661 The 6-joint ultrasonographic assessment: a valid, sensitive-to-change and feasible method 2012 May OBJECTIVE: Musculoskeletal US can be useful in monitoring RA. It can be time-consuming and there is no consensus in defining the joints to evaluate. We assessed the validity, sensitivity to change and feasibility of a reduced 6-joint US score in patients with RA starting therapy with an anti-TNF agent. METHODS: A group of consecutive RA patients starting etanercept were investigated. The patients underwent clinical evaluation, laboratory tests and US assessment at baseline and 3 months. A semi-quantitative score (0-3) was used to evaluate synovial effusion (SE), synovial proliferation (SP) and power Doppler (PD) signal in 12 joints. A process of data reduction, based on the frequency of synovial site involvement by US-SE, US-SP and US-PD signal, was conducted to investigate the validity of a 6-joint US assessment. RESULTS: Forty-five RA patients were evaluated. A significant decrease in all clinical, serological and 12-joint US parameters was found at follow-up. A significant correlation between changes in the DAS-28 and changes in the US scores in the 12-joint assessment was observed at follow-up (P < 0.001). A reduced 6-joint US score was obtained, including wrist, second MCP and knee joints of both sides, detecting US-SE in 97.78% of patients, US-SP in 100% of patients and positive US-PD in 100% of patients. The 6-joint US score showed a highly significant correlation with changes in DAS-28 (P < 0.001). The 6-joint evaluation was quick and easy to do. CONCLUSION: A 6-joint US assessment may be a valid, sensitive-to-change and feasible method for evaluating joint inflammation in RA.
22447883 Effects of glucocorticoid treatment on CD25⁻FOXP3⁺ population and cytokine-producing c 2012 Jul OBJECTIVES: To investigate CD25(-)FOXP3(+) cells in RA patients and their possible relationship with disease features and response to glucocorticoids (GCs). METHODS: Peripheral blood mononuclear cells were collected from 147 RA patients, 29 healthy controls and 75 SLE patients as disease controls. The proportion of CD4(+)FOXP3(+) cells with negative, low or high CD25 expression and the levels of IL-10-, TNF-α-, IL-17- and IFNγ-producing cells were assessed by flow cytometry. The presence of the high IL-10 genotype (-1082GG), associated with good response to GC, was determined by PCR amplification and hybridization with allele-specific fluorescently labelled probes. Data were related to treatment and clinical parameters. RESULTS: The CD25(-)FOXP3(+) population was significantly increased in RA patients and negatively correlated with DAS-28 and other disease parameters. The IL-10 genotype did not influence the frequency of these cells in controls or the entire RA group; however, GC-treated patient carriers of the high IL-10 genotype presented significantly higher levels of this population in addition to an increased percentage of IL-10-secreting cells and relatively low amounts of TNF-α-, IFN-γ- and IL-17-positive cells. Finally, a prospective study confirmed that genetically high IL-10 producers significantly increase CD25(-)FOXP3(+) cells after 6 months of GC treatment. CONCLUSION: The present study provides the first evidence of increased CD25(-)FOXP3(+) cells in RA patients, which were associated with disease activity and with GC treatment in carriers of the high IL-10 genotype, suggesting that this population plays a role in the clinical response to prednisone in RA.
20863170 Performance in leisure-time physical activities and self-efficacy in females with rheumato 2011 Sep The purpose of this study was to examine leisure-time physical activities (LTPAs) and their association with self-efficacy in females with rheumatoid arthritis (RA) (n = 238). Their self-reported performance in LTPAs was measured by the Interest Checklist and efficacy beliefs by using the Arthritis Self-Efficacy Scales (ASES). LTPAs were classified as active or less active according to how many LTPAs they performed. The participants had reduced their participation in LTPAs by almost one-third during the last year. Active individuals performed the vigorous activities more often, they had a higher level of education, were working to a significantly greater extent, and reported better function, higher scores on the self-efficacy scales, and lower joint pain and fatigue. Multivariate analyses demonstrated that a high level of LTPAs was independently related to less fatigue (OR 0.98, p = 0.004), positive self-efficacy in coping with RA functions (OR 1.03, p = 0.015), and higher employment level (OR 0.42, p = 0.039). Only a quarter of the responders were physically active in their leisure time in the present study. Less active individuals reduced their performance in LTPAs to a much higher degree than active individuals during the last year. Partaking in a high amount of LTPAs was related to less fatigue and higher efficacy beliefs.
21921094 Rheumatoid arthritis disease severity indices in administrative databases: a systematic re 2011 Nov OBJECTIVE: We aimed to systematically review rheumatoid arthritis (RA) disease severity indices for use in administrative healthcare databases. We also provide an overview of alternative methods to control for RA disease severity in administrative database research. METHODS: We conducted a systematic review of studies that developed/validated an index for RA disease severity using variables in administrative databases, and compared the convergent validity/reliability of the index with a standard measure of RA severity. RESULTS: After reviewing 539 articles, 2 studies were included. The claims-based index for RA severity (CIRAS) was developed in one study. Components of the CIRAS included tests for inflammatory markers, number of chemistry panels/platelet counts ordered, rheumatoid factor test, number of rehabilitation and rheumatology visits, and Felty's syndrome. The CIRAS correlated moderately well with a previously validated RA medical records-based index of severity. The second study assessed whether current and lifetime treatment with disease-modifying antirheumatic drugs and/or biologics accurately predicted RA severity, as measured by the patient-reported Patient Activity Scale (PAS). Treatment variables did not fully distinguish patients in the highest and lowest quartiles of PAS scores (67.2% correctly classified). CONCLUSION: Two claims-based indices of RA severity were identified but have some limitations for routine use. A concerted effort from experts in the field is needed to define, develop, and validate a widely applicable measure of RA disease severity for administrative database research.
22264800 Self-reported issues with driving in patients with chronic pain. 2012 Feb OBJECTIVE: To assess the driving habits, driving patterns, and barriers to driving reported by patients with chronic pain. DESIGN: Cross-sectional mail survey with self-administered questionnaires. SETTING: University-affiliated hospital. PARTICIPANTS: A sample of 223 patients seen in consultation by a physiatrist through the Chronic Pain Rehabilitation Service. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASUREMENTS: Percentage of subjects who were current drivers, percentage of subjects experiencing difficulty with driving, and driving characteristics. RESULTS: Response rate was 48.9%. Of the subjects, 79% were current drivers; of the nondrivers, 56% reported stopping driving because of chronic pain. A significantly greater percentage of nondrivers (80%) than drivers (62.9%) were women (P = .039). Nondrivers reported greater levels of pain than drivers (P = .027). The mean Pain Disability Index total score was significantly lower for drivers (42.3) than for nondrivers (48.7; P = .006). Of all subjects, 70% indicated that pain limited their driving in some manner; 41% of this group indicated that they experienced quite a bit or a great deal of difficulty driving. Factors that limited driving included pain (88.9%), fatigue (50.6%), limited joint mobility/stiffness (48.3%), and weakness (19.4%). The most frequently reported difficulties related to driving were sitting for any length of time (79.6%) and getting into the driver's seat (66.5%). Only 2.4% of current drivers had been referred for a driving assessment. CONCLUSIONS: Most people with chronic pain continue to drive and overall appear to have better functioning than those who cannot continue driving because of chronic pain. Despite being able to drive, a significant proportion of drivers with chronic pain are facing challenges not only with driving the vehicle but also with entering and positioning themselves within the vehicle. Our results suggest that chronic pain does have an impact on driving. However, it appears to be generally unrecognized as a factor for driving other than when the implications of opioid use are considered.
21874326 Tenascin-C fragments are endogenous inducers of cartilage matrix degradation. 2012 Sep Cartilage destruction is a hallmark of osteoarthritis (OA) and is characterized by increased protease activity resulting in the degradation of critical extracellular matrix (ECM) proteins essential for maintaining cartilage integrity. Tenascin-C (TN-C) is an ECM glycoprotein, and its expression is upregulated in OA cartilage. We aimed to investigate the presence of TN-C fragments in arthritic cartilage and establish whether they promote cartilage degradation. Expression of TN-C and its fragments was evaluated in cartilage from subjects undergoing joint replacement surgery for OA and RA compared with normal subjects by western blotting. The localization of TN-C in arthritic cartilage was also established by immunohistochemistry. Recombinant TN-C fragments were then tested to evaluate which regions of TN-C are responsible for cartilage-degrading activity in an ex vivo cartilage explant assay measuring glycosaminoglycan (GAG) release, aggrecanase and matrix metalloproteinase (MMP) activity. We found that specific TN-C fragments are highly upregulated in arthritic cartilage. Recombinant TN-C fragments containing the same regions as those identified from OA cartilage mediate cartilage degradation by the induction of aggrecanase activity. TN-C fragments mapping to the EGF-L and FN type III domains 3-8 of TN-C had the highest levels of aggrecan-degrading ability that was not observed either with full-length TN-C or with other domains of TN-C. TN-C fragments represent a novel mechanism for cartilage degradation in arthritis and may present new therapeutic targets for the inhibition of cartilage degradation.
21208248 Neutrophils of rheumatoid arthritis patients on anti-TNF-α therapy and in disease remissi 2011 Apr Neutrophils participate in the initiation and progression of rheumatoid arthritis (RA) although the exact mechanisms responsible for neutrophil accumulation in rheumatoid joints are not understood. This study compared the adhesive and chemotactic functions of neutrophils from RA patients in activity (DAS28 > 3.2) and not in activity (DAS28 < 2.6) and observed the effects of different treatment approaches on these functions. Neutrophils were isolated from healthy controls (CON), and patients with active or inactive RA in use of therapy not specific for RA (NSAIDs), in use of DMARDs and in use of anti-TNF-α therapy. Adhesive and chemotactic properties were evaluated using in vitro assays; adhesion molecule expression was assessed by flow cytometry and real-time PCR and circulating chemokines were determined by ELISA. No significant alterations in the adhesive and chemotactic properties of neutrophils from active RA were observed when compared to CON neutrophils, independently of treatment regimen. In contrast, neutrophils from RA patients in disease remission presented reduced adhesive properties and a lower spontaneous chemotactic capacity, in association with decreased adhesion molecule expression, although profiles of alterations differed for those patients on DMARDs and those on anti-TNF-α therapy. Circulating levels of the major neutrophilic chemokines, IL-8 and epithelial neutrophil activating peptide-78, were also significantly decreased in those patients demonstrating a clinical response. Remission of RA appears to be associated with ameliorations in aspects important for neutrophil adhesion and chemotaxis; whether these alterations contribute to decrease neutrophil migration to the synovial fluid, with consequent improvements in the clinical manifestations of RA, remains to be determined.
22241900 The influence of anti-TNF therapy upon incidence of keratinocyte skin cancer in patients w 2012 Jun OBJECTIVES: To compare the risk of keratinoctye skin cancer (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) in patients treated for rheumatoid arthritis (RA) compared with the general population, and to determine whether anti-tumour necrosis factor (TNF) therapy exacerbates this risk. METHODS: Patients with RA enrolled in the British Society for Rheumatology Biologics Register, a prospective national cohort established in 2001 to monitor the safety of anti-TNF, were followed until 2008. 11 881 patients treated with anti-TNF were compared with 3629 patients receiving non-biological disease-modifying antirheumatic drugs (nbDMARD). Standardised incidence ratios (SIR) were calculated for each cohort and rates between cohorts were compared using Cox proportional HR, adjusted using inverse probability of treatment weighting. RESULTS: SIR for skin cancer was increased in both cohorts compared with the English population: SIR 1.72 (95% CI 1.43 to 2.04) anti-TNF; 1.83 (95% CI 1.30 to 2.50) nbDMARD only. In patients without previous skin cancer, BCC incidence per 100 000 patient-years was 342 (95% CI 290 to 402) after anti-TNF and 407 (95% CI 288 to 558) after nbDMARD. HR after anti-TNF adjusted for treatment weighting was 0.95 (95% CI 0.53 to 1.71). SCC incidence per 100 000 patient-years: anti-TNF 53 (95% CI 33 to 79); nbDMARD 43 (95% CI 12 to 110); adjusted HR 1.16 (95% CI 0.35 to 3.84). CONCLUSIONS: Skin cancers were increased among treated patients with RA. No evidence was found that anti-TNF therapy exacerbates the risk of BCC or SCC but this cannot be excluded. Patients with RA should use sun protection and be monitored for skin cancer.
21777782 Arthroscopic ankle arthrodesis. 2011 Jun Arthroscopic ankle arthrodesis provides the surgeon with an alternative to traditional open techniques. Arthroscopic ankle arthrodesis has demonstrated faster union rates, decreased complications, reduced postoperative pain, and shorter hospital stays. Adherence to sound surgical techniques, particularly with regard to joint preparation, is critical for success. Although total ankle replacement continues to grow in popularity, arthroscopic ankle arthrodesis remains a viable alternative for the management of end-stage arthritic ankle.
22151604 SNPInterForest: a new method for detecting epistatic interactions. 2011 Dec 12 BACKGROUND: Multiple genetic factors and their interactive effects are speculated to contribute to complex diseases. Detecting such genetic interactive effects, i.e., epistatic interactions, however, remains a significant challenge in large-scale association studies. RESULTS: We have developed a new method, named SNPInterForest, for identifying epistatic interactions by extending an ensemble learning technique called random forest. Random forest is a predictive method that has been proposed for use in discovering single-nucleotide polymorphisms (SNPs), which are most predictive of the disease status in association studies. However, it is less sensitive to SNPs with little marginal effect. Furthermore, it does not natively exhibit information on interaction patterns of susceptibility SNPs. We extended the random forest framework to overcome the above limitations by means of (i) modifying the construction of the random forest and (ii) implementing a procedure for extracting interaction patterns from the constructed random forest. The performance of the proposed method was evaluated by simulated data under a wide spectrum of disease models. SNPInterForest performed very well in successfully identifying pure epistatic interactions with high precision and was still more than capable of concurrently identifying multiple interactions under the existence of genetic heterogeneity. It was also performed on real GWAS data of rheumatoid arthritis from the Wellcome Trust Case Control Consortium (WTCCC), and novel potential interactions were reported. CONCLUSIONS: SNPInterForest, offering an efficient means to detect epistatic interactions without statistical analyses, is promising for practical use as a way to reveal the epistatic interactions involved in common complex diseases.
22962687 SB1578, a novel inhibitor of JAK2, FLT3, and c-Fms for the treatment of rheumatoid arthrit 2012 Oct 15 SB1578 is a novel, orally bioavailable JAK2 inhibitor with specificity for JAK2 within the JAK family and also potent activity against FLT3 and c-Fms. These three tyrosine kinases play a pivotal role in activation of pathways that underlie the pathogenesis of rheumatoid arthritis. SB1578 blocks the activation of these kinases and their downstream signaling in pertinent cells, leading to inhibition of pathological cellular responses. The biochemical and cellular activities of SB1578 translate into its high efficacy in two rodent models of arthritis. SB1578 not only prevents the onset of arthritis but is also potent in treating established disease in collagen-induced arthritis mice with beneficial effects on histopathological parameters of bone resorption and cartilage damage. SB1578 abrogates the inflammatory response and prevents the infiltration of macrophages and neutrophils into affected joints. It also leads to inhibition of Ag-presenting dendritic cells and inhibits the autoimmune component of the disease. In summary, SB1578 has a unique kinase spectrum, and its pharmacological profile provides a strong rationale for the ongoing clinical development in autoimmune diseases.
22682794 Time trends in medication use and expenditures in older patients with rheumatoid arthritis 2012 Sep BACKGROUND: We sought to examine how expansions in insurance coverage of nonbiologic and biologic disease-modifying antirheumatic drugs affected the access, costs, and health status of older patients with rheumatoid arthritis. METHODS: We identified a nationally representative sample of older adults with rheumatoid arthritis in the 2000-2006 Medicare Current Beneficiary Survey (unweighted n=1051). We examined changes in disease-modifying antirheumatic drug use, self-reported health status, functional status (activities of daily living), and total costs and out-of-pocket costs for medical care and prescription drugs. Tests for time trends were conducted using weighted regressions. RESULTS: Between 2000 and 2006, the proportion of older adults with rheumatoid arthritis who received biologics tripled (4.6% vs 13.2%, P=.01), whereas the proportion of people who used a nonbiologic did not change. During the same period, the proportion of older patients with rheumatoid arthritis rating their health as excellent/good significantly increased (43.0% in 2000 to 55.6% in 2006; P=.015). Significant improvements occurred in activities of daily living measures of functional status. Total prescription drug costs (in 2006 US dollars) increased from $2645 in 2000 to $4685 in 2006, P=.0001, whereas out-of-pocket prescription costs remained constant ($842 in 2000 vs $832 in 2006; P=.68). Total medical costs did not significantly increase ($16,563 in 2000 vs $19,510 in 2006; P=.07). CONCLUSION: Receipt of biologics in older adults with rheumatoid arthritis increased over a period of time when insurance coverage was expanded without increasing patients' out-of-pocket costs. During this time period, concurrent improvements in self-reported health status and functional status suggest improved arthritis care.
21305513 Does cancer that occurs during or after anti-tumor necrosis factor therapy have a worse pr 2011 Jul OBJECTIVE: Tumor necrosis factor (TNF) may affect tumor development and spreading. While data on the incidence of cancer following anti-TNF therapy have been published, the purpose of this study was to examine the clinical presentation and outcome of cancers that develop during or after anti-TNF therapy. METHODS: By linking data from Swedish clinical registries of rheumatoid arthritis (RA) patients, including Anti-Rheumatic Therapy in Sweden (ARTIS), the Swedish Biologics Register, with nationwide data on hospitalizations and outpatient visits for RA, we assembled a cohort of 78,483 RA patients who were alive in 1999 or who entered the cohort thereafter. Of these, 8,562 patients started therapy with a biologic agent (98% started an anti-TNF) during the period from January 1, 1999 to December 31, 2007. Linkage to the Swedish Cancer Register and other registers identified first primary cancers occurring during 1999-2007 as well as post-cancer survival through March 31, 2009. Through this linkage, we identified 314 cancers in patients who were undergoing, or had a history of, treatment with biologic agents and 4,650 cancers in patients who were biologics-naive at the time of cancer diagnosis. The distributions of tumor stage among the biologics-exposed and the biologics-naive patients were compared. The relative risk of death among the biologics-exposed versus the 586 matched biologics-naive cancer cases were assessed by Cox regression analyses. Through chart review in a defined subset, we gathered additional clinical information and validated the diagnoses. RESULTS: For all cancers combined, the distribution of cancer stages at the time of cancer diagnosis was largely similar between those in the biologics-exposed and the matched biologics-naive groups. Based on the total of 113 deaths among those with cancer in the biologics-exposed group versus the 256 deaths among those with cancer in the biologics-naive group, the relative risk of death following cancer associated with exposure to anti-TNF was 1.1 (95% confidence interval 0.8-1.6). CONCLUSION: During routine care, cancers that occur following anti-TNF therapy are not characterized by any markedly altered stage at presentation or by altered post-cancer survival rates.