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ID PMID Title PublicationDate abstract
17907232 The importance of the disease process and disease-modifying antirheumatic drug treatment i 2007 Oct 15 OBJECTIVE: To evaluate the effect of disease-modifying antirheumatic drugs (DMARDs) on the likelihood of patients with rheumatoid arthritis (RA) developing septic arthritis (SA). METHODS: The United Kingdom General Practice Research Database (GPRD) was used to identify adults with RA, and age-, sex-, and practice-matched control subjects. Subjects were studied between 1987 and 2002. The risk of developing SA (excluding infected joint replacements) for individuals with RA was calculated and the effect of DMARD use determined. RESULTS: A total of 136,977 subjects (34,250 patients with RA, 102,747 controls) were identified. SA was identified in 345 subjects, of which 321 (236 in patients with RA, 85 in controls) cases occurred during the study period. The incidence rate of SA was 12.9 times higher in subjects with RA than in those without (95% confidence interval [95% CI] 10.1-16.5, P < 0.001). The incident rate ratios (IRRs) for developing SA while receiving DMARDs compared with receiving no DMARDs were different for different medications. Penicillamine (adjusted IRR 2.51, 95% CI 1.29-4.89, P = 0.004), sulfasalazine (adjusted IRR 1.74, 95% CI 1.04-2.91, P = 0.03), and prednisolone (adjusted IRR 2.94, 95% CI 1.93-4.46, P < 0.001) were associated with an increased incidence of SA when compared with not receiving any DMARD. The use of other DMARDs including methotrexate showed no such effect. CONCLUSION: Individuals with RA have an increased risk of developing SA. This increased risk can be attributed to both the disease process and the use of DMARDs.
17325736 Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheu 2007 Dec The folate antagonist methotrexate (MTX) is a drug currently used in the treatment of rheumatoid arthritis (RA). MTX enters the cells through the reduced folate carrier (RFC-1) and is activated to polyglutamates. Previous studies have shown that RFC-1 expression may influence the efficacy of therapy with MTX. The studies suggest that G80A polymorphism in RFC-1 is associated with altered folate/antifolate levels and the subjects carrying homozygous mutant 80AA genotype tend to have higher plasma folate and MTX concentrations and higher erythrocyte polyglutamate levels compared with those with the wild type or heterozygous genotype. It is possible that this polymorphism might influence MTX treatment outcome in patients with RA. In the present study, we examined the association between RFC-1 G80A polymorphism and treatment outcome in patients with RA administered MTX. The study was carried out on 174 patients diagnosed with RA treated with MTX (7.5-15.0 mg weekly) plus low doses of methylprednisone. The RFC-1 80G>A polymorphism (resulting in a histidine-to-arginine substitution at codon 27 of RFC-1) was detected using a polymerase chain reaction-restriction fragment length polymorphism method. The probability of remission of RA symptoms was 3.32-fold higher in carriers of 80AA genotype as compared with patients with 80GG genotype (P=0.021, OR=3.32, 95% CI: 1.26-8.79). The frequency of A allele among MTX responders was 62.1, compared to 47.8% in a group of poor MTX responders (P=0.013, OR=1.78, 95% CI: 1.13-2.81). Moreover, the increase of aminotransferase activity was noted more frequently in carriers of 80AA genotype. The present data suggest that evaluation of RFC-1 gene 80G>A polymorphism may be a useful tool to optimize MTX therapy in patients with RA.
16573350 Abatacept. 2006 Abatacept (Orencia) is the first in a new class of biologics known as selective costimulation modulators. It inhibits full activation of T cells and interacts with other cell types to affect additional mediators of the inflammatory cascade. The clinical efficacy of abatacept in patients with active rheumatoid arthritis, despite prior treatment with methotrexate or anti-tumor necrosis factor-alpha (anti-TNFalpha) therapies, has been investigated in two randomized, double-blind, placebo-controlled, multicenter, phase III trials of 6 or 12 months' duration. In these trials, patients received intravenous abatacept (fixed-dose regimen based on bodyweight) or placebo in addition to background disease-modifying anti-rheumatic drugs (DMARDs) other than anti-TNFalpha therapies. Relative to placebo, abatacept significantly improved signs and symptoms of disease assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria and specific improvement in physical function as measured by the Health Assessment Questionnaire Disability Index at 6 months and significantly slowed structural damage progression in joints at 12 months. Improvements in ACR 20, 50, and 70 response rates were maintained at the final assessment in the 12-month trial. Abatacept infusions were generally well tolerated. Acute infusion-related reactions occurred in 9% of abatacept and 6% of placebo recipients in phase III trials. Integrated safety data from five clinical trials showed that serious adverse events were reported in 13.6% of abatacept and 12.3% of placebo recipients and the incidence of serious infections was 3.0% and 1.9%. Abatacept administered with background biologic DMARDs appears to be less well tolerated than abatacept plus background nonbiologic DMARDs.
16355038 Computerized quantification of joint space narrowing and periarticular demineralization in 2006 Jan OBJECTIVES: The aim of our work was to evaluate digital x-ray radiogrammetry (DXR) for the quantification of disease-related periarticular demineralization and computerized analysis of joint space distances (JSDA) for the measurement of joint space narrowing as a new diagnostic method for the early detection of joint-associated alterations and for monitoring disease progression in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: Digital radiographs in 313 patients with varying severity of RA were performed annually and assessed by 2 radiologists using modified Larsen and also the Sharp scores within an observation period of 3 years. The hand radiographs underwent measurements of bone mineral density (BMD) and metacarpal index (MCI) by DXR, as well as computerized JSDA at the metacarpal-phalangeal articulation (JSD-MCP) for a cross-sectional and longitudinal study design. RESULTS: Both DXR-BMD (-29.6%; P < 0.01) and DXR-MCI (-31.0%; P < 0.01) revealed a notable reduction dependent on the severity of RA (from grade 1 to grade 5 of the modified Larsen score); the severity dependent decrease of mean JSD-MCP ranged from -31.9% (P < 0.01; Sharp erosion part) to -39.1% (P < 0.01) for the modified Larsen score. Over an observation period of 3 years, a significant decrease of DXR-BMD (-22.3%) and DXR-MCI (-23.3%) as well as JSD-MCP mean (-17.5%) was observed (P < 0.05), whereas an accentuated decline of DXR and JSDA parameters was verified for patients without disease-modifying antirheumatic drugs or methotrexate therapy. CONCLUSION: Computerized analysis of hand radiographs by DXR and JSDA is a promising approach to assess the severity and to monitor the progression of RA because DXR and JSDA are timely able to measure periarticular demineralization and also narrowing of JSD-MCP dependent on the severity, the medical treatment and the course of RA.
18391674 Prevalence and factors associated with metabolic syndrome in patients with rheumatoid arth 2008 Apr PURPOSE: To assess the frequency and factors associated with metabolic syndrome in adult female patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: During January and June 2006, 192 consecutive adult female patients seen during their scheduled appointment at the out-patient rheumatology clinic and meeting the American College of Rheumatology classification criteria for RA and SLE were invited to participate in this study. Sociodemographic, menopausal status, personal history of coronary heart disease, and physical activity were evaluated. According to the National Cholesterol Education Program Adult Treatment III (NCEP/ATP III), metabolic syndrome was defined as >or=3 of the following criteria: increased waist circumference (>88 cm or 35 inches), hypertriglyceridemia (>or=150 mg/dL), low (<40 mg/dL) high-density lipoprotein, hypertension, and high fasting glucose (>or=110 mg/dL). RESULTS: : One hundred-seven RA and 85 SLE patients with a mean age of 43 +/- 13 years were included in this study. The frequency of obesity and abnormal waist circumference were similar in RA and SLE patients. Two percent were underweight, 35% had a normal weight, 37% were overweight, and 25% were obese. The frequency of metabolic syndrome in RA and SLE patients was 17%. Metabolic syndrome was significantly associated with greater age, less education, lower income, and smoking. In RA patients, metabolic syndrome was significantly associated with a shorter treatment period with methotrexate, with pain, and with health assessment questionnaire scores. By multivariate logistic regression, the only statistically significant predictor of metabolic syndrome was smoking. CONCLUSIONS: The frequency of metabolic syndrome in RA and SLE patients was similar and associated with smoking. In RA patients, metabolic syndrome was related with pain and functional status, suggesting disease activity. A better control of disease activity may reduce the presence of metabolic syndrome and the risk of cardiovascular disease.
16395748 A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined w 2006 Jan OBJECTIVE: A placebo controlled, double-blind trial (DBT) was conducted for Japanese patients with active rheumatoid arthritis (RA) despite treatment with low dose methotrexate (MTX) to evaluate the efficacy and safety of infliximab. Extended treatment with infliximab was conducted in an open-label trial (OLT). METHODS: In the DBT, 147 patients were randomly assigned and treated with a placebo or 3 mg/kg or 10 mg/kg infliximab at Weeks 0, 2 and 6, combined with MTX. In the OLT, 129 patients from the DBT received 3 mg/kg infliximab every 8 weeks. RESULTS: The mean dose of MTX was 7.2 +/- 2.0 mg/week. Significantly more patients receiving 3 mg/kg (61.2%) and 10 mg/kg (52.9%)infliximab achieved a 20% improvement according to the American College of Rheumatology (ACR) criteria at Week 14, compared to placebo (23.4%) (p < 0.001). There was no significant difference in incidence of adverse events among the treatment groups. In patients receiving infliximab in the DBT, 11.6% of patients with serum infliximab just before the OLT developed antibodies to infliximab (ATI) in the OLT, whereas 62.2% of patients without serum infliximab did. In patients receiving placebo in the DBT, 43.9% developed ATI. CONCLUSION: The efficacy and safety of infliximab combined with low dose MTX were similar to those of the ATTRACT study. The data from the DBT and OLT also supported the importance of an induction treatment of infliximab, followed by a maintenance treatment without a long interval, giving stable serum concentrations in order to prevent formation of ATI.
18536334 [Case of miliary tuberculosis during treatment with infliximab for rheumatoid arthritis]. 2008 May A 70-year-old woman afflicted with rheumatoid arthritis was consulted another hospital because of fever and abnormality in chest X-ray. She had been treated with methotrexate and infliximab for seven months. She was diagnosed as methotrexate-induced pneumonia, and was administrated large therapeutic doses of corticosteroid, but finding of her chest X-ray exacerbated. Her sputum examination was positive for Mycobacterium tuberculosis complex by nucleic-acid amplification test, and she was diagnosed as miliary tuberculosis. She was treated with INH, RFP, EB, and PZA, and showed good clinical response to treatment. When infliximab is prescribed, we have to bear in mind possible complication of tuberculosis.
17092341 Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic 2006 The objective of this study was to investigate the interaction between levels of BAFF (B-cell activation factor of the tumour necrosis factor [TNF] family) and APRIL (a proliferation-inducing ligand) and B-cell frequencies in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) treated with the B-cell-depleting agent rituximab. Ten patients with SLE were treated with rituximab in combination with cyclophosphamide and corticosteroids. They were followed longitudinally up to 6 months after B-cell repopulation. Nine patients with RA, resistant or intolerant to anti-TNF therapy, treated with rituximab plus methotrexate were investigated up to 6 months after treatment. The B-cell frequency was determined by flow cytometry, and serum levels of BAFF and APRIL were measured by enzyme-linked immunosorbent assays. BAFF levels rose significantly during B-cell depletion in both patient groups, and in patients with SLE the BAFF levels declined close to pre-treatment levels upon B-cell repopulation. Patients with SLE had normal levels of APRIL at baseline, and during depletion there was a significant decrease. In contrast, patients with RA had APRIL levels 10-fold higher than normal, which did not change during depletion. At baseline, correlations between levels of B cells and APRIL, and DAS28 (disease activity score using 28 joint counts) and BAFF were observed in patients with RA. In summary, increased BAFF levels were observed during absence of circulating B cells in our SLE and RA patient cohorts. In spite of the limited number of patients, our data suggest that BAFF and APRIL are differentially regulated in different autoimmune diseases and, in addition, differently affected by rituximab treatment.
16947783 Relationship between genetic variants in the adenosine pathway and outcome of methotrexate 2006 Sep OBJECTIVE: Among patients with rheumatoid arthritis (RA), there is a high degree of interindividual variability in the degree of response to methotrexate (MTX) treatment. This study was undertaken to explore polymorphisms in genes contributing to antiinflammatory adenosine release as novel predictors of MTX treatment outcome. METHODS: In 205 patients with newly diagnosed RA, 5 polymorphisms in 5 genes coding for enzymes related to the release of adenosine were analyzed. All patients received standardized MTX treatment (up to 25 mg per week orally), combined with folic acid. MTX efficacy was evaluated by the Disease Activity Score (DAS) and compared among genotypes. The association between MTX-related adverse events and genotype was also assessed. The following polymorphisms were determined: AMPD1 34C>T, ATIC 347C>G, ITPA 94C>A, MTR 2756A>G, and MTRR 66A>G. When significant differences were found by chi-square analysis, odds ratios (ORs) and 95% confidence intervals were calculated. RESULTS: Patients carrying the AMPD1 34T allele, ATIC 347CC, or ITPA 94CC were more likely to have a good clinical response, as defined by a DAS of < or =2.4 (OR [95% confidence interval] 2.1 [1.0-4.5], 2.5 [1.3-4.7], and 2.7 [1.1-8.1], respectively). The likelihood of a good clinical response was increased if patients possessed all 3 favorable genotypes (OR 27.8 [95% confidence interval 3.2-250]). Regarding toxicity, only ATIC G allele carriers experienced a greater frequency of adverse events (OR 2.0 [95% confidence interval 1.1-3.7]). CONCLUSION: Polymorphisms in the AMPD1, ATIC, and ITPA genes are associated with good clinical response to MTX treatment. These findings indicate that genotyping may help in the identification of patients who will benefit most from MTX treatment and may assist clinicians in making treatment decisions regarding patients with recent-onset RA.
17302286 [Pharmacogenomics of antirheumatic drugs and personalized medicine for rheumatoid arthriti 2007 Feb Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints. The inflammatory process causes a significant disability and may involve internal organs. The efficacy of disease modifying anti rheumatic drugs is widely accepted. However, the outcome of the treatment with these agents is known to vary among patients. Recently, the pharmacogenomic studies on methotrexate, sulfasalazine and tumor necrosis factor-alpha inhibitors have been reported, suggesting that the pharmacogenomic approach may be useful for the treatment of RA. Although there are points to be considered before the translation of the pharmacogenomic date into clinical practice, pharmacogenomics is considered to be an important tool for development of individualized medicine in the treatment of RA.
18383390 Results of a two-year followup study of patients with rheumatoid arthritis who received a 2008 Apr OBJECTIVE: To evaluate the efficacy, radiographic changes, and safety of abatacept and methotrexate therapy through 2 years in a long-term extension of a previously published 1-year study. METHODS: Patients who received placebo during year 1 were switched to abatacept. Patients taking abatacept continued to take it. Efficacy and safety were assessed through 2 years. RESULTS: Of 539 patients enrolled in the initial 1-year study, 488 completed 1 year of the long-term extension (2% discontinued for lack of efficacy). At 2 years, patients taking abatacept had maintained their responses on the American College of Rheumatology (ACR) improvement criteria and the Disease Activity Score in 28 joints (DAS28; using the C-reactive protein [CRP] level), as well as their physical function (according to the Health Assessment Questionnaire [HAQ] disability index [DI]) and health-related quality of life (HRQOL; assessed with the Short Form 36 [SF-36] health survey), that were observed at the end of the double-blind period (year 1 versus year 2 values were 81.9% versus 80.3% for ACR 20% improvement, 25.4% versus 30.9% for a DAS28 [CRP] of <2.6, 71.8% versus 66.8% for the HAQ DI, and 9.7 versus 10.6 and 7.3 versus 7.2, respectively, for the mean change in the physical and mental components summary scores of the SF-36). In the abatacept group, post hoc analysis demonstrated further inhibition of radiographic progression during year 2 (57% reduction in mean change of total score in year 2 versus year 1; P<0.0001), and minimal radiographic progression was observed (mean change in total score from baseline was 1.1 and 1.6 at year 1 and 2, respectively). Rates of adverse events (AEs) and severe AEs were consistent throughout the cumulative period. CONCLUSION: The improvements in signs and symptoms, physical function, and HRQOL observed after 1 year of abatacept treatment were maintained through 2 years of treatment. This durability was accompanied by a safety profile consistent with that in the double-blind portion of the study. Radiographic progression was further inhibited in year 2 compared with year 1, suggesting an increasing effect of abatacept on the inhibition of structural damage in year 2.
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.
18368468 Reversible infliximab-related lymphoproliferative disorder associated with Epstein-Barr vi 2008 A 63-year-old woman with active rheumatoid arthritis (RA) had been treated with methotrexate and prednisolone. She developed cervical lymph node swelling 30 months after the initiation of infliximab therapy. A computed tomography revealed cervical and mediastinal lymph node swelling and multiple nodules (up to 13 mm in diameter) in the lungs. A lymph node biopsy showed infiltration of numerous Hodgkin-like and Reed-Sternberg-like cells. Immunohistological studies showed that these cells were positive for CD15, CD30, and Epstein-Barr virus (EBV) latent membrane protein. In site hybridization revealed the presence of EBV RNA in the nuclei of these cells. EBV DNA was detected in the biopsy specimen by southern blot analysis. She was diagnosed as having EBV-associated lymphoproliferative disorder (LPD). Immunodeficiency-associated LPD related with infliximab therapy was considered. Cessation of infliximab therapy only led to dramatic regression of LPD. This case illustrates that EBV-associated LPDs can occur as part of infliximab adverse effects in patients with RA.
17875551 Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in compl 2008 Jan OBJECTIVE: To analyse the effects of leflunomide and methotrexate treatment on matrix metalloproteinase (MMP) activity levels in alpha2 macroglobulin/MMP (alpha2M/MMP) complexes in the systemic circulation of rheumatoid arthritis (RA) patients. METHODS: A total of 102 RA patients from a prospective, double-blind, randomised clinical trial comparing leflunomide and methotrexate were selected; clinical data and blood samples were collected at baseline, at 4 months and at 1 year. Serum MMP activity levels in alpha2M were quantified using low molecular weight fluorogenic substrates, indicating the proportion of activated MMPs that were not inhibited by specific tissue inhibitors of MMP (TIMP). RESULTS: Patients had active disease as shown by high disease activity score (DAS, mean of 6.9 and 7.0 for methotrexate and leflunomide patients respectively), which was reduced over the study period (4.2 and 5.2 respectively, p<0.001). In leflunomide-treated patients a significant reduction of MMP activity levels was observed as early as at the 4 months timepoint persisting thereafter, whereas in methotrexate-treated patients the reduction was seen at 1 year. CONCLUSION: The results show that systemic levels of activated MMPs are reduced in RA patients upon exposure to leflunomide or methotrexate.
18055472 Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-ce 2008 Aug OBJECTIVES: This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo. The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score (based on erythrocyte sedimentation rates; DAS28 (ESR)) for the abatacept vs placebo groups at day 197. METHODS: Patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) were randomised 3:3:2 to abatacept ( approximately 10 mg/kg every 4 weeks, n = 156), infliximab (3 mg/kg every 8 weeks, n = 165), or placebo (every 4 weeks, n = 110) and background MTX. Safety and efficacy were assessed throughout the study. RESULTS: Similar patient demographics and clinical characteristics were present at baseline between groups, with mean scores of approximately 1.7 for HAQ-DI and 6.8 for DAS28 (ESR). At 6 months, mean changes in DAS28 (ESR) were significantly greater for abatacept vs placebo (-2.53 vs -1.48, p<0.001) and infliximab vs placebo (-2.25 vs -1.48, p<0.001). For abatacept vs infliximab treatment at day 365, reductions in the DAS28 (ESR) were -2.88 vs -2.25. At day 365, the following response rates were observed for abatacept and infliximab, respectively: American College of Rheumatology (ACR) 20, 72.4 and 55.8%; ACR 50, 45.5 and 36.4%; ACR 70, 26.3 and 20.6%; low disease activity score (LDAS), 35.3 and 22.4%; DAS28-defined remission, 18.7 and 12.2%; good European League Against Rheumatism (EULAR) responses, 32.0 and 18.5%; and Health Assessment Questionnaire Disability Index (HAQ-DI), 57.7 and 52.7%. Mean changes in physical component summary (PCS) were 9.5 and 7.6, and mental component summary (MCS) were 6.0 and 4.0, for abatacept and infliximab, respectively. Over 1 year, adverse events (AEs) (89.1 vs 93.3%), serious AEs (SAEs) (9.6 vs 18.2%), serious infections (1.9 vs 8.5%) and discontinuations due to AEs (3.2 vs 7.3%) and SAEs (2.6 vs 3.6%) were lower with abatacept than infliximab. CONCLUSIONS: In this study, abatacept and infliximab (3 mg/kg every 8 weeks) demonstrated similar efficacy. Overall, abatacept had a relatively more acceptable safety and tolerability profile, with fewer SAEs, serious infections, acute infusional events and discontinuations due to AEs than the infliximab group. TRIAL REGISTRATION NUMBER: NCT00095147.
17642237 [CTLA4-Ig (abatacept)]. 2007 Jul Although tumor necrosis factor (TNF) antagonists have dramatically improved the outcome of patients with rheumatoid arthritis (RA), some of the patients do not respond or cannot tolerate these drugs. Abatacept is a recombinant fusion protein containing components of IgG and cytotoxic T-lymphocyte-associated antigen-4 that inhibit costimulatory signal from antigen presenting cells and prevent activation of T cells. Several clinical trials have demonstrated the excellent efficacy and safety of abatacept in patients with RA who are resistant to methotrexate or TNF antagonists. Abatacept improved clinical signs and symptoms and quality of life of patients with RA and also retarded their radiological progression of structural damage of affected joints. The safety concerns, especially for infections and malignancies, are raised and should be strictly monitored in clinical trials and future clinical practice in Japan as well as in Western countries.
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.
19096851 Preliminary study on the immunologic background of good clinical outcome in rheumatoid art 2009 Jun This preliminary study focuses on early peripheral cellular immune changes after 1 month therapy with leflunomide, in 18 patients with severe rheumatoid arthritis, previously treated with methotrexate. A good clinical outcome of disease was documented and we showed that a particular target of short-time leflunomide therapy in rheumatoid arthritis was the peripheral innate immune system (NK cells and the population of granulocytes developing phagocytosis and superoxide anion production when challenged ex vivo with zymosan particles). Meanwhile, the high inter-individual variability of adaptive immunity required data analysis in subgroups of patients. We showed that the abnormal increase of peripheral leukocytes counts, or the decrease towards normal values of the CD4:CD8 lymphocytes ratio, or the inhibition of uridine uptake by ex vivo activated lymphocytes were consistent with a positive clinical evolution, proved by the reduction of tender/swollen joints, morning stiffness duration or acute phase response. We emphasized that significant benefits of short-term leflunomide therapy were associated with functional suppression of peripheral B lymphocytes. Hence, the positive evolution of rheumatoid arthritis patients seemed to be specifically linked to early drug-induced changes of trafficking or uridine metabolism of mononuclear cells.
17469099 Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a doubl 2007 May OBJECTIVE: To determine whether patients with undifferentiated arthritis (UA; inflammatory, nontraumatic arthritis that cannot be diagnosed using current classification criteria) benefit from treatment with methotrexate (MTX). METHODS: The PRObable rheumatoid arthritis: Methotrexate versus Placebo Treatment (PROMPT) study was a double-blind, placebo-controlled, randomized, multicenter trial involving 110 patients with UA who fulfilled the American College of Rheumatology (ACR) 1958 criteria for probable RA. Treatment started with MTX (15 mg/week) or placebo tablets, and every 3 months the dosage was increased if the Disease Activity Score was >2.4. After 12 months, the study medication was tapered and discontinued. Patients were followed up for 30 months. When a patient fulfilled the ACR criteria for RA (primary end point), the study medication was changed to MTX. Joint damage was scored on radiographs of the hands and feet. RESULTS: In 22 of the 55 patients (40%) in the MTX group, UA progressed to RA compared with 29 of 55 patients (53%) in the placebo group. However, in the MTX group, patients fulfilled the ACR criteria for RA at a later time point than in the placebo group (P = 0.04), and fewer patients showed radiographic progression over 18 months (P = 0.046). CONCLUSION: This study provides evidence for the efficacy of MTX treatment in postponing the diagnosis of RA, as defined by the ACR 1987 criteria, and retarding radiographic joint damage in UA patients.
18409565 [A patient with Mycobacterium avium lung disease presenting with rapid, progressive and mu 2008 Mar An 80-year-old woman presented with rapid, progressive and multiple cavitary lesions in both lungs. Rheumatoid arthritis had been diagnosed and been treated with prednisolone (5 mg/day) and bucillamine since 1996. Due to worsening of arthralgia, methotrexate (6 mg/week) and leflunomide (10 mg/day) had been added to the medication since 2003. In April 2005, her chest radiography revealed multiple cavities and nodules predominantly in both upper lung fields, although she complained of no respiratory symptoms. No pathogenic organisms were found, and the cavitary and nodular shadows were increased rapidly within the next 2 months. Therefore, the patient was referred to our hospital in July 2005. Repeat microbiologic findings of sputum were negative for bacteria and fungi, except for Mycobacterium avium (M. avium). She was given a diagnosis of M. avium lung disease, and it seemed to be associated with her compromised status caused by disease modifying anti-rheumatic drugs (DMARDs). She was then successfully treated with combined chemotherapy employed clarithromycin, rifampicin, ethambutol and streptomycin. So far, rapid and progressive deterioration of non-tuberculous mycobacterial lung disease accompanied with an intake of DMARDs had not been reported in Japan. An increase of M. avium complex lung disease in the elderly is now becoming a problem among respiratory physicians. This case highlights the fact that patients who are scheduled to be given DMARDs, particularly elderly case, should be considered to be at an elevated risk of developing non-tuberculous mycobacterial (NTM) lung disease, and the risk of NTM infection should be excluded before prescribing drugs.