Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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16802345 | Inflammatory cytokine regulation of transgene expression in human fibroblast-like synovioc | 2006 Jul | OBJECTIVE: An ideal gene transfer vector for chronic inflammatory diseases such as rheumatoid arthritis (RA) would provide local transgene expression only when the disease is active. To determine whether adeno-associated virus (AAV) possesses this ability, the effects of inflammatory cytokines on transgene expression were evaluated in human RA fibroblast-like synoviocytes (FLS). METHODS: Human FLS were infected with AAV in the presence or absence of inflammatory cytokines or synovial fluid obtained from patients with RA. Transgene expression was monitored by either enzyme-linked immunosorbent assay or flow cytometry. Transgene messenger RNA (mRNA) was measured by real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Inflammatory cytokines increased transgene expression in FLS by up to 60-fold. Synovial fluid from patients with RA, but not from patients without arthritis, was also able to increase expression in synoviocytes. Protein expression correlated with transgene mRNA levels. The enhanced expression required the continued presence of cytokines because, upon removal, transgene expression returned to baseline levels. Expression could be repeatedly reinduced by reexposure to cytokines. The effect was not promoter specific and was demonstrated to be phosphatidylinositol 3-kinase-dependent. CONCLUSION: These results suggest that expression of a therapeutic transgene can be controlled by the presence of inflammation following AAV gene transfer, making it an attractive vector for chronic inflammatory diseases such as RA. | |
17024343 | Association of a BTLA gene polymorphism with the risk of rheumatoid arthritis. | 2006 Nov | B and T lymphocyte attenuator (BTLA) is an immuno-inhibitory receptor with the ability to deliver inhibitory signal for suppressing lymphocyte activation. To test the potential association of the human BTLA gene with the development of rheumatoid arthritis (RA), a genetic case-control association study was conducted, by using a single nucleotide polymorphism (SNP), C+800T SNP, in the exon 5 of the human BTLA gene for genotyping 93 RA patients and 294 normal control individuals. The results showed that there is statistically significant difference in the genotype distributions between RA and control groups (p = 0.022). When compared with the heterozygous genotype (C/T genotype), the homozygous genotype (C/C or T/T genotype) appears to confer the increased risk of the RA susceptibility with the odds ratio of 1.88 (p = 0.015). These data indicate the significant association between the C+800T SNP in the BTLA gene with the RA susceptibility. | |
16337520 | Complications of operative fixation of proximal humeral fractures in patients with rheumat | 2005 Nov | Currently, there is no information in the literature on operative treatment of proximal humeral fractures in patients with rheumatoid arthritis. Eleven patients underwent osteosynthesis of the proximal humerus from December 1987 to December 2002. Nine patients were treated for acute fractures, and two were treated for nonunions. Four had loss of initial anatomic reduction, two were treated nonoperatively with resultant malunion, and two required revision fixation. Two patients with symptomatic pseudarthrosis were treated with internal fixation and bone grafting. Both had complications (1 requiring hemiarthroplasty after painful nonunion and 1 with chondrolysis). All patients with acute fractures achieved fracture union. One patient had an excellent result, four had satisfactory results, and six had an unsatisfactory result. Patients and treating physicians should be aware of the high rate of complications and unsatisfactory results in patients with rheumatoid arthritis who undergo operative treatment of proximal humeral fractures. | |
16467035 | Hand function in women and men with early rheumatoid arthritis. A prospective study over t | 2006 Jan | OBJECTIVE: To describe the course of hand function in women and men during the first 3 years after diagnosis of recent-onset rheumatoid arthritis (RA), to investigate sex differences in hand function, and to study correlations between and within hand function assessments. METHODS: A total of 276 patients (69% women) with RA of a maximal duration of 12 months were recruited to the study. Hand function was assessed by the Grip Ability Test (GAT) and Signals of Functional Impairment (SOFI). Peak and average grip force over 10 s in the right and left hand was measured by an electronic device. RESULTS: Hand function was affected at diagnosis, but had improved significantly at the 3-months' follow-up and then remained stable (but still affected) in both women and men. As assessed by SOFI, hand function was worse in men than in women, whereas women had significantly lower grip force. GAT, grip force, and SOFI correlated weakly. The average and peak values of grip force correlated strongly, as did the grip force in the right and the left hand. CONCLUSION: Hand function was profoundly affected at diagnosis of RA, but improved significantly within 3 months and remained stable (but still affected) over 3 years. As expected, women on average had significantly lower grip force than men. | |
15593093 | Heterogeneity testing in meta-analysis of genome searches. | 2005 Feb | Genome searches for identifying susceptibility loci for the same complex disease often give inconclusive or inconsistent results. Genome Search Meta-analysis (GSMA) is an established non-parametric method to identify genetic regions that rank high on average in terms of linkage statistics (e.g., lod scores) across studies. Meta-analysis typically aims not only to obtain average estimates, but also to quantify heterogeneity. However, heterogeneity testing between studies included in GSMA has not been developed yet. Heterogeneity may be produced by differences in study designs, study populations, and chance, and the extent of heterogeneity might influence the conclusions of a meta-analysis. Here, we propose and explore metrics that indicate the extent of heterogeneity for specific loci in GSMA based on Monte Carlo permutation tests. We have also developed software that performs both the GSMA and the heterogeneity testing. To illustrate the concept, the proposed methodology was applied to published data from meta-analyses of rheumatoid arthritis (4 scans) and schizophrenia (20 scans). In the first meta-analysis, we identified 11 bins with statistically low heterogeneity and 8 with statistically high heterogeneity. The respective numbers were 9 and 6 for the schizophrenia meta-analysis. For rheumatoid arthritis, bins 6.2 (the HLA region that is a well-documented susceptibility locus for the disease) and 16.3 (16q12.2-q23.1) had both high average ranks and low between-study heterogeneity. For schizophrenia, this was seen for bin 3.2 (3p25.3-p22.1) and heterogeneity was still significantly low after adjusting for its high average rank. Concordance was high between the proposed metrics and between weighted and unweighted analyses. Data from genome searches should be synthesized and interpreted considering both average ranks and heterogeneity between studies. | |
15674784 | A visual analogue scale for assessment of the impact of rheumatoid arthritis in the hand: | 2005 Jan | A visual analogue scale was developed by French rheumatologists to measure the impact caused by rheumatoid arthritis of the hand (VAS-Hand). This article reports the use of the measure. First, the validity of the VAS-Hand was investigated by interviewing patients to understand how they interpreted and answered these questions. Second, the measure was compared with disability, pain, and impairment measures to determine whether it provided additional information. Finally, the repeatability of the measure was defined as within 1.5 points out of ten. The visual analogue scale of handicap from rheumatoid arthritis of the hand provides different information than do health status or disability questionnaires, or strength and motion assessment. The responsiveness of the VAS-Hand is under investigation in a longitudinal study. | |
17877113 | Costimulatory molecule CD154 in systemic lupus erythematosus and rheumatoid arthritis. The | 2006 Jan | SLE is a systemic autoimmune disease characterized by B cell hyperactivity. Evidence from the last years has shown that B cells play a key role in the development of the immune response. The interaction of CD40 on B cells with its ligand CD154 on activated T cells provides a costimulatory signal that induces T dependent B cell proliferation and differentiation with subsequent antibody production. Moreover, CD154 can act as a cytokine, in addition to its main role to mediate the interactions between T and CD40+ target cells. This review focuses on the multiple roles of CD154 in systemic lupus erythematosus and rheumatoid arthritis and its involvement in the humoral immunity disregulation of patients with these diseases. It also takes in consideration the most recent therapeutic perspectives regarding the use of monoclonal antibodies against CD154, which might be a powerful tool in the treatment of these diseases in the future. | |
16817978 | Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthr | 2006 | As indicators of responsiveness to a tumour necrosis factor (TNF)alpha blocking agent (infliximab) are lacking in rheumatoid arthritis, we have used gene profiling in peripheral blood mononuclear cells to predict a good versus poor response to infliximab. Thirty three patients with very active disease (Disease Activity Score 28 >5.1) that resisted weekly methotrexate therapy were given infliximab at baseline, weeks 2 and 6, and every 8th week thereafter. The patients were categorized as responders if a change of Disease Activity Score 28 = 1.2 was obtained at 3 months. Mononuclear cell RNAs were collected at baseline and at three months from responders and non-responders. The baseline RNAs were hybridised to a microarray of 10,000 non-redundant human cDNAs. In 6 responders and 7 non-responders, 41 mRNAs identified by microarray analysis were expressed as a function of the response to treatment and an unsupervised hierarchical clustering perfectly separated these responders from non-responders. The informativeness of 20 of these 41 transcripts, as measured by qRT-PCR, was re-assessed in 20 other patients. The combined levels of these 20 transcripts properly classified 16 out of 20 patients in a leave-one-out procedure, with a sensitivity of 90% and a specificity of 70%, whereas a set of only 8 transcripts properly classified 18/20 patients. Trends for changes in various transcript levels at three months tightly correlated with treatment responsiveness and a down-regulation of specific transcript levels was observed in non-responders only. Our gene profiling obtained by a non-invasive procedure should now be used to predict the likely responders to an infliximab/methotrexate combination. | |
17192561 | Dialogue between the brain and the immune system in inflammatory arthritis. | 2006 Nov | The crosstalk between the brain and the immune system in inflammatory arthritis is exerted mainly through the activation or downregulation of the hypothalamic-pituitary-adrenal (HPA), the hypothalamic-pituitary-gonadal (HPG), and the hypothalamic-autonomic nervous system (HANS) axes. In this review, we will present an overview of the most recent data regarding the regulation of these complex pathways of neuroendocrine response during the different phases of inflammatory arthritides such as rheumatoid arthritis (RA). Furthermore, the effect of the most recently available biologic therapies like anti-tumor necrosis factor (TNF-a) on the neuroendocrine function in patients with RA will be reviewed. | |
17091903 | [Omega-3 and health]. | 2006 Sep | N-3 PUFA (omega-3), and the n-6 PUFA (omega-6) are essential fatty acids. They must be absorbed by alimentation and play a very important role in the coagulation (inhibition of platelets aggregation) and in the inflammatory reaction (anti-inflammatory effects). Their effects have been studied in different sicknesses. In cardiovascular diseases, particularly in coronary diseases, studies demonstrated a decreased mortality in populations who eat an omega-3 rich diet or who take an omega-3 supplement. Among others, sudden death after myocardial infarction is decreased. In inflammatory diseases an effect seem to be found in some studies. In rheumatoid arthritis a decrease of different biological markers of inflammation and in some case a clinical improvement has been noticed. It may be the same in COPD. On the other hand, they seem not to give any protection against cancer in general. At this moment the recommendations for healthy people are to eat twice a week fat fish and to take omega-3 rich oils. For pathological cases, recommendations exist only for coronary disease: 1 g of fish oils : mixture of eicosapentaenoic and docosahexaenoic acids (EPA/DHA) should be given after a myocardial infarction. | |
17288976 | Inflammation-induced bone loss: can it be prevented? | 2006 Nov | Inflammatory synovitis induces profound bone loss and OCLs are the instrument of this destruction. TNF blockers have an established role in the prevention of inflammatory bone loss in RA; however, not all patients respond to anti-TNF therapy and side effects may prevent long-term treatment in others. The B-cell--depleting antibody rituximab and the T-cell costimulation blocker abatacept are emerging as major treatment options for patients who are resistant to anti-TNF [96,97]. Proof-of-concept studies demonstrate that targeting RANK-mediated osteoclastogenesis prevents inflammatory bone loss and clinical application has only just begun. The efficacy of RANKL inhibition has been witnessed in trials of Denosumab, and RANKL-neutralizing antibodies are likely to become the treatment of choice for blocking RANKL in RA [77,78]. A major limitation of RANKL antagonism is that it does not treat synovitis. Therefore, anti-RANKL therapy most likely will be used in the context of MTX therapy. There is uncertainty about the possible extraskeletal adverse effects of long-term effects of long-term RANKL blockade. In particular, anti-RANKL therapy could jeopardize dendritic cell function or survival. The demonstrable role of OCLs in inflammation-induced bone loss also invites a reconsideration of the new BPs for bone protection [98]. Studies of ZA in preclinical models indicate that bone protection is comparable to that afforded by OPG. One possible caveat is that intravenous BPs are linked to jaw osteonecrosis [99], although the incidence is confined mainly to intensive treatment in the oncology setting. Although pulsed PTH stimulated bone formation in arthritic models, it has yet to be proven clinically in the context of powerful OCL inhibition with TNF or RANKL antagonists. With strategies that normalize OCL numbers, clinicians are poised to accomplish effective prevention of inflammation-induced bone loss. | |
17108315 | Pathogenesis and prevention of bone loss in patients who have kidney disease and receive l | 2007 Jan | The coexistence of kidney disease with a need for immunosuppressive therapy leads to the convergence of several threats to bone. These comprise general effects of the primary disease, e.g., inflammatory state, more specific effects of acute renal failure or chronic kidney disease, and effects of therapies. Multisystem inflammatory disease that requires immunosuppression is associated frequently with kidney damage, and any reduction of kidney function that takes the patient into or beyond chronic kidney disease stage 2 for more than a short time is likely to have a negative impact on bone health. Bone mineral density frequently is low and fracture rates are high, although correlations often are poor. Chronic inflammation leads to local and systemic imbalance between bone formation and resorption. Upregulation of NF-kappabeta ligand (RANKL) and variable downregulation of osteoprotegerin are implicated, and bone health may improve in response to treatment of the inflammatory state. Certain immunosuppressive agents, especially glucocorticoids and calcineurin inhibitors, contribute further to bone loss. Antiresorptive agents such as bisphosphonates are used widely and, although able to prevent loss of bone mineral density, have uncertain effects on fracture rates. Augmentation of anabolic activity is desirable but elusive. Synthetic parathyroid hormone is untested but has potential. Manipulation of the RANKL/osteoprotegerin system now is feasible using antibodies to RANKL or synthetic osteoprotegerin. In the future, manipulation of the calcium-sensing receptor using calcimimetic or calcilytic agents may allow the anabolic effects of parathyroid hormone to be harnessed to good effect. With all of these therapies, it will be important to assess response in relation to important clinical end points such as fracture. | |
15719708 | Rationale for testing the cardiovascular risk for patients with COX-2 inhibitors on the ba | 2005 | Owing to the selective inhibition of PGI2 synthesis, treatment with COX-2 inhibitors constitutes a potential risk for the increased occurrence of thrombotic cardiovascular incidents and of the first-time occurrence or a deterioration in pre-existing heart failure. Elderly patients, particularly those with a history of ischemic heart disease, hypertension or heart failure, are at risk. One key indication for selective COX-2 inhibitors is the chronic treatment of patients suffering from rheumatoid arthritis or osteoarthritis. However, these patients have an excess cardiovascular mortality, which relates particularly to cardiovascular incidents or heart failure. The use of nonselective antiphlogistic drugs and COX-2 inhibitors is associated with a higher potential risk in these patient groups. In essence, more than 80 million patients worldwide were treated with rofecoxib up to its voluntary withdrawal. The high number of patients who are still being treated with COX-2 inhibitors or for whom the use of COX-2 inhibitors is planned justifies the use of a biochemical marker which, as a screening instrument, is initially designed to recognize the patients who are "ill" despite the lack of symptoms. In asymptomatic patients with NT-proBNP levels below the cut-off, high-risk patients require further work-up. Recognition of these risk factors is easily accomplished considering the case history and the results of an established cardiovascular risk score (e.g. PROCAM score). These risk patients should then also be referred for intensive diagnostic work-up. On the other hand, symptomatic patients or those with high NT-proBNP levels should primarily be referred for more extensive cardiovascular diagnosis before a decision is taken concerning the use of COX-2 inhibitors. As an integral part of this extensive work-up the determination of NT-proBNP can help to improve the accuracy of diagnosis and prognostic assessment. With the exception of patients showing symptoms of an unstable coronary heart disease, imminent cerebral ischemia, uncontrolled arterial hypertension or decompensated heart failure, the use of a COX-2 inhibitor is possible provided special caution is exercised. Termination of treatment is advisable if there is a clinical deterioration of specific symptoms or signs in those patients (product information). Follow-up with NT-proBNP (monitoring) can be helpful in detecting imminent cardiac decompensation at an earlier stage in order to take suitable countermeasures. | |
17014004 | Retention rates of tumor necrosis factor blockers in daily practice in 770 rheumatic patie | 2006 Dec | OBJECTIVE: Tumor necrosis factor (TNF) blockers are efficacious in clinical trials in rheumatic diseases. However, their efficacy in daily practice, depending on the specific diagnosis or the use of concomitant therapy, remains to be confirmed. Our objective was to evaluate TNF blocker retention rates and their predisposing factors in daily practice. METHODS: Retrospective evaluation of all TNF blocker therapies in one center. Retention rate was evaluated using a Kaplan-Meier survival data analysis technique in which the event was discontinuation of the drug due to inefficacy or toxicity with log-rank tests and a Cox proportional-hazards regression model. RESULTS: From 1997 to 2004, 770 patients with inflammatory rheumatism received at least one TNF blocker; 142 received more than one agent (975 treatment courses: 493 etanercept, 335 infliximab, 147 adalimumab). The underlying disease was mainly rheumatoid arthritis (RA), found in 57.1% of patients, and spondyloarthropathies (SpA) in 37.7%. The percentage of patients receiving the same treatment at Month 12, 24, and 36 was 64.0%, 50.3%, and 39.4%, respectively. No difference between the 3 TNF blockers was found (p = 0.48). The retention rate was longer for the first treatment course [hazard ratio (HR) 2.17, 95% confidence interval (95% CI) 1.82-2.58, p < 0.0001]; longer for patients with SpA (HR 1.60, 95% CI 1.20-2.13, p = 0.001); and longer without concomitant DMARD (HR 0.70, 95% CI 0.51-0.97, p = 0.03). CONCLUSION: Our results indicate a lower retention rate of TNF blockers in daily practice compared with clinical trials, with no difference between the 3 currently available agents. Moreover, results suggest greater benefit in SpA. The role of concomitant DMARD remains to be confirmed. | |
16078320 | Neuropsychiatric syndromes in patients with systemic lupus erythematosus and rheumatoid ar | 2005 Aug | OBJECTIVE: The cause of neurologic (N) and psychiatric (P) syndromes in patients with systemic lupus erythematosus (SLE) is mutifactorial and includes primary immunopathogenic mechanisms, nonspecific sequelae of chronic disease, and concurrent illnesses. We compared the prevalence, diversity, and clinical significance of NP syndromes in patients with SLE and rheumatoid arthritis (RA). METHODS: Fifty-three patients with SLE were matched by age and sex to 53 patients with RA attending ambulatory clinics in a single academic medical center. All fulfilled the American College of Rheumatology (ACR) classification criteria for either SLE or RA. Cumulative NP manifestations were determined using the ACR nomenclature and case definitions for 19 NP syndromes. Depression and anxiety were measured by the Hospital Anxiety and Depression Scales (HADS) and symptoms of cognitive dysfunction were assessed by the Cognitive Symptoms Inventory (CSI). Health related quality of life (HRQOL) was evaluated by the SF-36 and fatigue by a 10 point Likert scale. RESULTS: The patients were well matched with regard to age, sex, disease duration, and years of education. There were no significant differences in self-reported HRQOL, fatigue, anxiety, depression, and cognitive symptoms between the 2 groups. The proportion of patients with cumulative NP events was higher in RA than in SLE patients (47% vs 28%; p = 0.045), and of these the occurrence of multiple NP events in individual patients was comparable in both groups (SLE 53%; RA 48%; p = 0.75). Fifty-five percent and 66% of NP events occurred prior to the diagnosis of SLE and RA, respectively. NP events common to both SLE and RA patients were headaches, mood disorders, acute confusional states, anxiety, cerebrovascular disease, and cognitive dysfunction. Seizures and demyelinating syndrome occurred only in SLE patients, but were rare. Depression scores (HADS) were significantly higher in SLE patients with a history of cumulative NP events compared to RA patients with NP events (p = 0.02). Similarly, symptoms of cognitive dysfunction (CSI) were more common in SLE patients with a history of NP manifestations (p = 0.02). However, there were no significant differences in SF-36 subscale or fatigue scores between SLE and RA patients with cumulative NP events. CONCLUSION: NP syndromes, regardless of etiology, are common in both SLE and RA patients. SLE patients with NP syndromes report more symptoms of depression and cognitive dysfunction compared to RA patients with NP syndromes, but do not report significantly poorer HRQOL. These results emphasize the presence of non-disease-specific causes of NP manifestations in SLE patients, which should be acknowledged in future studies of pathogenesis and treatment. | |
16542466 | Fish oil: what the prescriber needs to know. | 2006 | There is a general belief among doctors, in part grounded in experience, that patients with arthritis need nonsteroidal anti-inflammatory drugs (NSAIDs). Implicit in this view is that these patients require the symptomatic relief provided by inhibiting synthesis of nociceptive prostaglandin E2, a downstream product of the enzyme cyclo-oxygenase (COX), which is inhibited by NSAIDs. However, the concept of 'safe' NSAIDs has collapsed following a multiplicity of observations establishing increased risk for cardiovascular events associated with NSAID use, especially but not uniquely with the new COX-2-selective NSAIDs. This mandates greater parsimony in the use of these agents. Fish oils contain a natural inhibitor of COX, reduce reliance on NSAIDs, and reduce cardiovascular risk through multiple mechanisms. Fish oil thus warrants consideration as a component of therapy for arthritis, especially rheumatoid arthritis, in which its symptomatic benefits are well established. A major barrier to the therapeutic use of fish oil in inflammatory diseases is ignorance of its mechanism, range of beneficial effects, safety profile, availability of suitable products, effective dose, latency of effects and instructions for administration. This review provides an evidence-based resource for doctors and patients who may choose to prescribe or take fish oil. | |
17055211 | Genetic basis of rheumatoid arthritis. | 2006 Dec | Rheumatoid arthritis (RA) is a clinically heterogeneous condition with a complex aetiology in which environmental and genetic factors are implicated. The contribution of human leukocyte antigen (HLA) genes, particularly the HLA-DRB1 gene, to RA genetic predisposition was the first described, and remains as the best characterised single genetic risk factor contributing to RA. However, it has been estimated that only 30% of the genetic contribution to RA can be attributed to HLA genes and it is suggested that other non-HLA genes may play a relevant role in RA susceptibility. Linkage studies and association studies are the two main strategies used in the investigation of genetic factors contributing to complex genetic traits. In this work we review the progress made in the field of RA genetics, focusing mainly on the contribution of candidate gene association studies to the dissection of RA genetic risk factors. | |
17050366 | Contrast-enhanced dynamic magnetic resonance imaging of finger joints in osteoarthritis an | 2006 Oct | PURPOSE: To investigate a two-compartment kinetic model applied to the dynamic time course of contrast enhancement as a method to differentiate between finger-joint synovitis in established osteoarthritis (OA) and rheumatoid arthritis (RA). MATERIAL AND METHODS: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of one hand in 19 patients and six healthy volunteers was undertaken. Eight patients had OA of the hand and eleven patients had RA. From the signal intensity curves, the three parameters Kps (endothelial transfer constant), Kep (elimination rate constant from extracellular space back to plasma) and Kel (elimination rate constant from plasma by renal excretion) were calculated. RESULTS: The rate constant Kps showed the best separation between the groups with significantly higher values in the RA group compared to the OA group (P<0.005) and in the OA group compared to the control group (P<0.005). Significantly higher values of Kep were also found in the RA group compared with the OA group (P<0.005). CONCLUSION: DCE-MRI may provide useful information that can help differentiate synovitis in OA from synovitis in RA. | |
17493521 | Not all "quality-adjusted life years" are equal. | 2007 Jun | BACKGROUND: There is evidence that utility elicitation methods used in the calculation of quality-adjusted life years (QALYs) yield different results. It is not clear how these differences impact economic evaluations. METHODS: Using a mathematical model incorporating data on efficacy, costs, and utility values, we simulated the experiences of 100,000 hypothetical rheumatoid arthritis patients over 10 years (50,000 exposed to infliximab plus methotrexate [MTX] and 50,000 exposed to MTX alone). QALYs, were derived from the Health Utilities Index 2 and 3 (HUI2 and HUI3), the Short Form 6-D (SF-6D), and the Euroqol 5-D (EQ-5D). Incremental cost-utility ratios were determined using each instrument to calculate QALYs and the results were compared using cost-effectiveness acceptability curves. RESULTS: Using the different utility measurement methods, the mean difference in QALYs between the infliximab plus MTX and MTX groups ranged from a high of 1.95 QALYs (95% CI=1.93-1.97) using the HUI3 to 0.89 QALYs (95% CI=0.88-0.91) using the SF-6D. Adopting the commonly cited value of society's willingness to pay for a QALY of $50,000, 91% of the simulations favored the cost utility of infliximab plus MTX when using the HUI3 to calculate QALYs. However, when using the EQ-5D, HUI2, or the SF-6D utility values to calculate QALYS, the proportion of simulations that favored the cost utility of infliximab were 63%, 45%, and 12%, respectively. CONCLUSION: Depending on the method for determining utility values used in the calculation of QALYs, very different incremental cost-utility ratios are generated. | |
16977346 | NOD2 allele variants in patients with rheumatoid arthritis. | 2007 Jun | Recent reports have proven the importance of genetic factors and inflammation in the pathogenesis of rheumatoid arthritis (RA). In the current study, the frequency of NOD2/CARD15 gene variants (R702W, G908R, and L1007fsinsC) was examined in a group of 243 RA patients and 220 healthy controls. There were no statistically significant differences in distribution of NOD2 variant alleles between RA patients and controls. Moreover, there was no significant association between NOD2 variant alleles and joint erosions, extraarticular manifestations, rheumatoid factor, number of swollen and tender joints, and erythrocyte sedimentation rate. The results of the present study suggest that NOD2 allele variants have no significant influence on RA susceptibility, activity, and severity. |