Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 12175730 | Soluble HLA-DR levels in serum are associated with therapy and genetic factors in rheumato | 2002 Sep | As rheumatoid arthritis (RA) is an HLA-DR associated autoimmune disease and soluble HLA-DR (sHLA-DR) molecules have the capacity to regulate the immune response, we studied the sHLA-DR levels in RA patients in view of therapy modalities and clinical and biologic parameters of disease activity. For this sHLA-DR concentrations from 87 RA patients were determined by a sensitive enzyme-linked immunoabsorbent assay (ELISA) format. There was a weak but significant correlation between sHLA-DR levels and disease activity (r 0.186 to 0.287, p < 0.004 to < 0.001). The mean serum sHLA were not significantly different between groups with or without corticosteroids, or undergoing therapy with different disease modifying antirheumatic drugs. However, patients treated with a combination of methotrexate and prednisolone have lower sHLA-DR (206 +/- 21 ng/ml, n = 34) compared with the mean value for all other samples (306 +/- 16, n = 217, p < 0.001). This corresponded with significantly lower EULAR pain and swelling scores, ESR and rheumatoid factor (RF) by latex fixation (p < 0.02 to 0.001) in the former, compared with the latter group. Furthermore, sHLA-DR was, respectively, 267 +/- 15 ng/ml (n = 182) in samples from patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs), and 358 +/- 31 (n = 72) without NSAIDs (p < 0.01). Lower sHLA-DR with NSAIDs contrasted with significantly higher scores for pain, swelling, CRP, and RF by latex fixation and by Waaler-Rose test (p < 0.05 to 0.001). Comparison of subgroups with or without the shared epitope of RA disease (Q)R/KRAA within the HLA-DR beta1-chain confirmed significantly higher parameters of disease activity and sHLA-DR in the presence of this disease associated epitope in our patients. Different mechanisms appear to be involved in sHLA-DR production or release, as their level correlates positively with disease activity under combined therapy with corticosteroids and methotrexate, but decreases with higher disease activity in patients treated with NSAIDs. | |
| 12421111 | Etanercept: an updated review of its use in rheumatoid arthritis, psoriatic arthritis and | 2002 | Etanercept is a subcutaneously administered biological response modifier that binds and inactivates tumour necrosis factor-alpha, a proinflammatory cytokine. In patients with early active rheumatoid arthritis, etanercept 25mg twice weekly was associated with a more rapid improvement in disease activity and a significantly greater cumulative response than methotrexate over 12 months of treatment in a randomised, double-blind trial. In addition, etanercept recipients showed a slower rate of radiographic progression and a more rapid improvement in quality of life than methotrexate recipients. The efficacy of etanercept was maintained at 3 years' follow-up. Etanercept was also significantly better than placebo at reducing disease activity in patients who had an inadequate response to previous treatment with disease-modifying antirheumatic drugs (DMARDs) in several well controlled trials. At study end (after 3 or 6 months' treatment), the percentage of patients achieving an American College of Rheumatology 20% (ACR20) response with etanercept (25mg or 16 mg/m(2) twice weekly) was 59 to 75% as monotherapy and 71% in combination with methotrexate; corresponding placebo response rates were 11 to 14% and 27%, respectively. Response has been maintained in patients who continued treatment for up to 5 years. In patients with psoriatic arthritis, etanercept 25mg twice weekly significantly reduced disease activity and improved skin lesions in two double-blind, placebo-controlled, 12- to 24-week trials. In the 24-week study, ACR20 response rates (50 vs 13%), psoriatic arthritis response rates (70 vs 23%) and the median improvement in skin lesions (33 vs 0%) were significantly greater in etanercept than in placebo recipients. In patients with polyarticular-course juvenile rheumatoid arthritis, etanercept resulted in improvements in all measures of disease activity and was significantly more effective than placebo at reducing disease flare. Eighty percent of patients receiving etanercept achieved a >or=30% reduction in disease activity over 7 months of treatment, and this was maintained for up to 2 years in a trial extension. Etanercept was generally well tolerated in children and adults in clinical trials; the most commonly occurring adverse effects included injection site reactions, infection, headache, rhinitis and dizziness. In conclusion, etanercept has emerged as an important new treatment option in inflammatory arthritis. Etanercept provides rapid and sustained improvements in disease activity in patients with early and DMARD-refractory rheumatoid arthritis and has been shown to inhibit radiographic progression in those with early disease. Well controlled studies have also demonstrated the efficacy of etanercept in patients with psoriatic arthritis or polyarticular-course juvenile rheumatoid arthritis. | |
| 15001324 | Therapeutic effect of the combination of etanercept and methotrexate compared with each tr | 2004 Feb 28 | BACKGROUND: Etanercept and methotrexate are effective in the treatment of rheumatoid arthritis but no data exist on concurrent initiation or use of the combination compared with either drug alone. We aimed to assess combination treatment with etanercept and methotrexate versus the monotherapies in patients with rheumatoid arthritis. METHODS: In a double-blind, randomised, clinical efficacy, safety, and radiographic study, 686 patients with active rheumatoid arthritis were randomly allocated to treatment with etanercept 25 mg (subcutaneously twice a week), oral methotrexate (up to 20 mg every week), or the combination. Clinical response was assessed by criteria of the American College of Rheumatology (ACR). The primary efficacy endpoint was the numeric index of the ACR response (ACR-N) area under the curve (AUC) over the first 24 weeks. The primary radiographic endpoint was change from baseline to week 52 in total joint damage and was assessed with the modified Sharp score. Analysis was by intention to treat. FINDINGS: Four patients did not receive any drug; thus 682 were studied. ACR-N AUC at 24 weeks was greater for the combination group compared with etanercept alone and methotrexate alone (18.3%-years [95% CI 17.1-19.6] vs 14.7%-years [13.5-16.0], p<0.0001, and 12.2%-years [11.0-13.4], p<0.0001; respectively). The mean difference in ACR-N AUC between combination and methotrexate alone was 6.1 (95% CI 4.5-7.8, p<0.0001) and between etanercept and methotrexate was 2.5 (0.8-4.2, p=0.0034). The combination was more efficacious than methotrexate or etanercept alone in retardation of joint damage (mean total Sharp score -0.54 [95% CI -1.00 to -0.07] vs 2.80 [1.08 to 4.51], p<0.0001, and 0.52 [-0.10 to 1.15], p=0.0006; respectively). The mean difference in total Sharp score between combination and methotrexate alone was -3.34 (95% CI -4.86 to -1.81, p<0.0001) and between etanercept and methotrexate was -27 (-3.81 to -0.74, p=0.0469). The number of patients reporting infections or adverse events was similar in all groups. INTERPRETATION: The combination of etanercept and methotrexate was significantly better in reduction of disease activity, improvement of functional disability, and retardation of radiographic progression compared with methotrexate or etanercept alone. These findings bring us closer to achievement of remission and repair of structural damage in rheumatoid arthritis. | |
| 12375317 | Longitudinal measurement of methotrexate liver concentrations does not correlate with live | 2002 Oct | OBJECTIVES: In patients with rheumatoid arthritis (RA), we examined whether methotrexate (MTX) and MTX polyglutamate accumulation in the liver correlated with clinical efficacy or clinical/laboratory toxicity. We also began preliminary examination of a new histologic index of liver histology (the Iowa Score) relative to the Roenigk grading system. METHODS: Forty patients with RA participated in a prospective, double blind, 3.5 year study of MTX treatment. Liver biopsies, liver MTX and MTX polyglutamate concentrations, laboratory tests, evaluation of disease activity, and evaluation of adverse events were done prospectively at baseline and at 1, 2, and 3.5 years. Biopsies were examined using the Roenigk grading system and an additional histological scoring system. Radiochemical ligand binding assays and HPLC methods were used to measure MTX and MTX polyglutamates. Statistical analysis included ANOVA, linear regression, and logistic regression modeling. RESULTS: No significant changes in the mean values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, albumin, or hemoglobin occurred. A significant percentage of patients had at least one abnormal alkaline phosphatase, AST, or ALT (25 to 52%), although most abnormalities were small and transient. Histological abnormalities did not progress using either the Roenigk or the Iowa score. The last abnormal AST, the number of abnormal AST and ALT, and female sex correlated with histological liver abnormalities (r2 = 0.41) using a new preliminary histologic scoring system (the Iowa Score). Amount of alcohol use correlated with fatty change, and the MTX dose at biopsy was associated with liver histological abnormalities (p = 0.03 and 0.049, respectively). Total liver MTX concentrations were stable from Year 1 to Year 3.5 and the percentage of higher order polyglutamates was relatively high (38 to 56%) relative to monoglutamates. No correlation of these concentrations with clinical response or toxicity, histology, or liver function tests could be documented. CONCLUSION: This analysis describes the accumulation and stabilization of MTX concentrations in the liver and examined correlations between MTX liver concentrations, patient demographics, liver histology, concomitant medications, and disease activity. No such correlations were found, decreasing the likelihood that MTX concentrations in serum would be useful measures to predict significant hepatotoxicity. | |
| 12355477 | A pilot randomized trial comparing CD34-selected versus unmanipulated hemopoietic stem cel | 2002 Sep | OBJECTIVE: Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA. METHODS: Thirty-three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease-modifying agent were enrolled in the trial. The patients received high-dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months. RESULTS: All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent-to-treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34-selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34-selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)-positive patients had an increase in RF titer prior to recurrence of disease. CONCLUSION: HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment-resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34-selected cells. Larger studies are needed to confirm these findings. | |
| 15318821 | [Effects of immunosuppressive therapy on cellular immunity status in elderly patients with | 2004 Apr | The article presents the findings of the immunological study of 57 elderly patients with rheumatoid arthritis, which had been given for a long period of time methotrexate (MT) and sulfasaline (SF). It was established that MT and SF basic therapy have led to progressive decreasing in absolute and relative quantity and an average diameter of CD4+, CD8, CD16, CD19 lymphocytes. It also resulted in lowering proliferative response of mononuclear lymphocytes (ML) to mitogens, increasing spontaneous and Fas-induced apoptosis of ML. The study revealed peculiarities of cellular immunity alterations in the patients with rheumatoid arthritis who developed infectious complication of the basic therapy. A prognostic role and critical values of the absolute and relative content of natural killers, structure and size of nucleus of natural killers and cytotoxic T-cells, spontaneous and Fas-induced apoptosis with regard to the risk of infectious complications of MT and SF therapies was established in elderly patients with RA. | |
| 12428224 | Association of baseline levels of markers of bone and cartilage degradation with long-term | 2002 Nov | OBJECTIVE: The known risk factors for radiologic progression in rheumatoid arthritis (RA) are not optimally discriminative in patients with early disease who do not have evidence of radiologic damage. We sought to determine whether urinary C-terminal crosslinking telopeptide of type I (CTX-I) and type II (CTX-II) collagen (markers of bone and cartilage destruction, respectively) are associated with long-term radiologic progression in patients with early RA. METHODS: This was a prospective study of 110 patients with early RA who were participating in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) clinical trial and followup study, a randomized controlled trial comparing the efficacy of oral pulse prednisolone, methotrexate, plus sulfasalazine with sulfasalazine alone. We investigated the relationship between baseline levels of urinary CTX-I and CTX-II and the mean annual progression of joint destruction over a median of 4 years, as measured by changes in the modified Sharp score (average of 2 independent readers). RESULTS: In multivariate logistic regression analysis, baseline urinary CTX-I and CTX-II levels in the highest tertile were the strongest predictors of radiologic progression (Sharp score increase >2 units/year; odds ratio 7.9 and 11.2, respectively), independently of treatment group, erythrocyte sedimentation rate (ESR), Disease Activity Score in 28 joints, rheumatoid factor (RF), and baseline joint damage (Sharp score). The likelihood ratios for a positive test were 3.8 and 8.0 for CTX-I and CTX-II, respectively, which compared favorably with the likelihood ratios for the ESR (3.0), baseline joint damage (1.6), and RF (1.8). When patients were grouped according to the presence (Sharp score >/=4, n = 49) and absence (Sharp score <4, n = 61) of joint damage at baseline, CTX-I and CTX-II levels were predictive only in those without baseline joint damage (odds ratio 14.9 and 25.7, respectively). CONCLUSION: High baseline levels of urinary CTX-I and CTX-II independently predict an increased risk of radiologic progression over 4 years in patients with early RA, especially those without radiologic joint damage. Urinary CTX-I and CTX-II may be useful for identifying individual RA patients at high risk of progression very early in the disease, before erosions can be detected radiographically. Such patients may be in special need of treatments that inhibit bone and cartilage degradation. | |
| 15096329 | Estimated prediagnosis radiological progression: an important tool for studying the effect | 2005 Jan | OBJECTIVE: To determine if intrapatient comparisons between prediagnosis and subsequent radiological progression could be used to assess effects of DMARDs in an RA inception cohort. PATIENTS AND METHODS: 149 non-randomised patients with newly diagnosed RA in four groups were analysed: patients treated with (a) methotrexate (n = 56); (b) sulfasalazine (n = 55); (c) auranofin (n = 19); and (d) controls who were poor treatment responders (n = 19). Radiographs were quantified using the Larsen erosion score. The prediagnosis radiological progression from the onset of RA symptoms to diagnosis was calculated and compared with the observed progression rate during the first year after diagnosis while receiving DMARD treatment. RESULTS: Mean (SD) disease duration from onset of symptoms until diagnosis was 6.7 (4.0) months. Mean (SD) baseline Larsen score was 13.2 (9.3), giving a mean (SD) estimated prediagnosis progression rate of 23.6 (12.4) Larsen score units/year. Control and auranofin groups showed radiological progression after diagnosis similar to the progression predicted by prediagnosis progression rates. Patients receiving methotrexate or sulfasalazine showed a marked reduction (71% and 73%, respectively; p<0.001) in radiographic progression compared with prediagnosis progression. CONCLUSIONS: Prediagnosis rates of radiological progression can be used quantitatively to obtain information on the potential efficacy of DMARDs, and indicate that methotrexate and sulfasalazine, but not auranofin, significantly retard radiographic damage in the first year after diagnosis. | |
| 15570633 | Enhanced Fcgamma receptor I, alphaMbeta2 integrin receptor expression by monocytes and neu | 2004 Dec | OBJECTIVE: To investigate platelet and leukocyte activation and interaction in patients with rheumatoid arthritis (RA) and the effect of methotrexate (MTX) or anti-tumor necrosis factor-a (TNF-a) treatment on these variables. METHODS: Four-color flow cytometry analysis was performed for quantitative measurement of platelet (P-selectin, PAC-1) and leukocyte (CD11b, CD64) activation markers and estimation of percentage of leukocyte-platelet complexes in whole blood in 20 patients with RA before and after 6 weeks of therapy and in 20 controls. In addition, measures of soluble P-selectin (sP-selectin), beta-thromboglobulin, fibrinogen, prothrombin fragment 1+2, D-dimer, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), and TNF-a and tender and swollen joint counts were carried out. RESULTS: Before therapy, PAC-1 binding, expression of CD11b and CD64 on monocytes and neutrophils, circulating levels of monocyte (CD11b+ or CD64+)-platelet complexes, monocyte-PAC-1+ platelet complexes, CRP, ESR, IL-6, TNF-a, fibrinogen, D-dimer and sP-selectin were significantly higher in RA patients compared to controls. The anti-TNF-a therapy significantly reduced levels of monocyte-PAC-1+ platelet complexes, sP-selectin, CRP, ESR, IL-6, TNF-a, fibrinogen, and D-dimer and tender and swollen joint counts. CD64 expression on monocytes was significantly decreased by MTX therapy. PAC-1 binding was not inhibited by MTX or anti-TNF-a. CONCLUSION: Increased platelet and leukocyte activation and increased formation of leukocyte-platelet complexes in patients with RA suggest a status of simultaneous activation of the immune and hemostatic systems. | |
| 14969075 | Role of biologics in early arthritis. | 2003 Sep | Recent advances in the management and treatment of rheumatoid arthritis (RA) have provided evidence for the importance of early diagnosis and treatment of the disease. Biological therapy with monoclonal antibodies, including anti-tumor necrosis factor (TNF) agents have shown major efficacy in terms of disease activity and outcome of inflammatory arthritis in trials. Interest has focused on the treatment of early rheumatoid arthritis with anti-TNF agents to induce long-term impact on outcome. A major study of etanercept versus methotrexate (MTX) showed some benefit at one year for the etanercept group, but long-term data have shown greater benefit. Two double-blind placebo-controlled studies of infliximab in patients with early RA yielded promising data, showing the possibility of a true 'window of opportunity' with long-term benefit from a short term treatment period. Aggressive treatment by anti-TNF agents as well as combination therapies of disease modifying anti-rheumatic drugs (DMARDs) in patients with very early disease would be a logical approach to be investigated in the future. | |
| 15345503 | Methotrexate ameliorates T cell dependent autoimmune arthritis and encephalomyelitis but n | 2005 Apr | OBJECTIVE: To investigate the mode of action of methotrexate (MTX) in different types of models for rheumatoid arthritis (RA) and multiple sclerosis (MS). METHODS: Models for RA and MS were selected known to have different pathogenesis--that is, fibroblast induced arthritis in SCID mice, collagen induced arthritis (CIA), anticollagen II antibody induced arthritis (CAIA), and experimental autoimmune encephalomyelitis (EAE) in (Balb/c x B10.Q)F1 and B10.Q mice, and Pristane induced arthritis in DA rats (PIA). The MTX treatment was started 1 day after the onset of disease and continued for 14 days to compare effects on the different models. RESULTS: All models known to be critically dependent on T cell activation (CIA, PIA, and EAE) were effectively down regulated by titrated doses of MTX. In contrast, no effects were seen on fibroblast induced arthritis or CAIA. No effects were seen on the levels of anticollagen II antibodies in the CIA experiment. CONCLUSION: The data show that MTX has strong ameliorative effect on both classical models of RA, like CIA and PIA, but also on a model for MS, EAE. It also suggests that MTX operates only in diseases which are preceded by, and dependent on, T cell activation. A comparison of CAIA and CIA suggested that MTX operates independently of arthritogenic antibodies. These results demonstrate that different animal models reflect the complexity of the corresponding human diseases and suggest that several models should be used for effective screening of new therapeutic agents. | |
| 11894837 | Insufficiency fractures in patients with chronic inflammatory joint diseases. | 2002 Jan | OBJECTIVE: To describe the typical sites of stress fractures in the lower extremities and pelvis in rheumatoid patients (rheumatoid arthritis, juvenile chronic arthritis, psoriatic arthritis, ankylosing spondylitis). METHODS: Thirty-three patients with 52 stress fractures [mean age 44 years (range 11-73)] were studied at the authors' institution when they were being treated for their rheumatic diseases. Fourteen patients had RA, 9 JCA, 5 PsoA, and 5 SPA. Stress fractures were detected from patient documents and from series radiographs in suspected cases. In some cases magnetic resonance imaging was also performed. RESULTS: One patient presented with 5 fractures, 2 patients with 4 and 3 fractures, and 7 patients with 2 fractures each. Other patients (n = 19) had only one fracture each. The metatarsal (MT) bones were the most common site of involvement. Twenty-five of the 52 fractures were located on MT I-V. The second and third most common sites were thefibula (n = 13) and tibia (n = 6). All fractures of the lower tibia or fibula were associated with valgus malalignment of the ankle. CONCLUSION: If a patient with rheumatic disease experiences sudden and unexplained pain localised in the forefoot, above the ankle, below the knee, or in the pelvis, a stress fracture should be suspected. Patients with severe osteoporosis, high-load corticosteroid or methotrexate therapy, or marked joint deformity are at high risk of developing stress fracture. | |
| 15033655 | True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin alpha? | 2004 Oct | BACKGROUND: The combination of methotrexate and the anti-tumour necrosis factor alpha (TNFalpha) antibody infliximab is a very effective treatment for rheumatoid arthritis (RA). However, a proportion of patients are not responsive to this treatment. Inefficacy may represent a TNFalpha independent disease or insufficient drug at the site of action. CASE REPORT: A patient with RA resistant to repeated high dose infliximab infusions and intra-articular infliximab into an inflamed knee is described. No beneficial clinical effect was observed. Pre-injection arthroscopic biopsy of the study knee demonstrated TNFalpha staining but also confirmed the presence of lymphotoxin alpha (LTalpha or TNFbeta) on immunohistochemistry. Subsequent treatment with etanercept (which blocks LTalpha as well as TNFalpha) resulted in clinical remission of disease. CONCLUSION: This case suggests that resistance to TNF blockade may occur when TNFalpha is not the dominant inflammatory cytokine and suggests that LTalpha may have a pathogenic role in RA. | |
| 12041674 | Epstein-Barr virus-associated B-cell type non-Hodgkin's lymphoma with concurrent p53 prote | 2002 May | A Japanese male patient received various medications for his long-standing rheumatoid arthritis (stage IV, class II). He developed a mass on the right anterior chest wall after being treated with methotrexate (MTX) for 4 months. A biopsy of the mass showed it to be Epstein Barr virus (EBV)-associated lymphoma of B-cell phenotype stage IE (bulky mass), with positive EBV-encoded small RNAs (EBERs) in situ hybridization, EBV latent membrane protein-1 (LMP-1) negative, EB nuclear antigen-2 (ERNA-2) negative, CD20/L26 (+), CD45RO/UCHL-1 (-). A single band of the joined termini of the EBV genome was demonstrated in DNA extracted from the mass, suggesting a clonal disorder of the mass. Immunostaining of the mass with p53 antibody was also positive. With discontinuation of MTX and administration of chemotherapy, the tumor disappeared but recurred after 3 months. This case suggests that concordant p53 expression and latent EBV infection may play an important role in the pathogenesis of lymphomas arising in patients with rheumatoid arthritis who are immunosuppressed with MTX. | |
| 12510368 | [Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 recept | 2002 Dec | Anakinra, a recombinant human interleukin-1 receptor antagonist offers a new potent treatment for rheumatoid arthritis(RA). It is administered as a daily single subcutaneous injection. Recent randomized, double-blind, placebo-controlled trials revealed that anakinra significantly reduces the signs and symptoms of RA, reduces joint destruction, and is safe and tolerated. It was also revealed that anakinra is more potent when used in combination with methotrexate. | |
| 15524495 | Etanercept: a pharmacoeconomic review of its use in rheumatoid arthritis. | 2004 | Etanercept (Enbrel), which inhibits the activity of tumour necrosis factor-alpha, is indicated in the treatment of patients with active rheumatoid arthritis (RA). A lifetime cost-utility analysis in patients with severe disease-modifying antirheumatic drug (DMARD)-resistant RA in the UK suggested that etanercept is associated with acceptable cost-utility ratios relative to traditional nonbiological DMARDs. In a 12-month cost-utility study in Spain, etanercept was predicted to be dominant over infliximab plus methotrexate in patients with active, refractory RA with regards to the cost per QALY gained and cost per American College of Rheumatology (ACR) 20 response achieved. In short-term cost-effectiveness analyses conducted in the US, the cost effectiveness of etanercept relative to other treatments in patients with methotrexate-naive or -resistant RA depends on whether predicted incremental cost-effectiveness ratios of at least USD 41,900 per ACR 20 response or USD 34,800 per ACR 70 weighted response over a 6-month period are considered acceptable (1999 values). The relative efficacy and cost effectiveness of etanercept and other biological DMARDs will be clarified when appropriate data from directly comparative clinical and/or long-term pharmacoeconomic studies become available. Etanercept may prevent or delay disability, which may produce reductions in nondrug costs that could help offset its acquisition cost. | |
| 15381644 | Declines in mortality from acute myocardial infarction in successive incidence and birth c | 2004 Sep 28 | BACKGROUND: Patients with rheumatoid arthritis are at high risk for acute myocardial infarction (AMI). The treatment of rheumatoid arthritis has become more intensive over the past 2 decades, resulting in tighter control of inflammation and lower levels of disability. The impact of this on atherosclerotic cardiovascular diseases is not known. METHODS AND RESULTS: Death rates from AMI in a cohort of 3862 patients with rheumatoid arthritis followed up from 1980 to 1997 were studied. Time trends in AMI mortality among successive incidence and birth cohorts were examined by use of multivariable Poisson regression models and by comparing standardized mortality ratios. The mean age was 56 years in this predominantly female cohort (76%), and median disease duration was 6.5 years. During the period of observation, the use of methotrexate increased substantially, whereas that of prednisone was relatively stable. Over the 22,209 person-years of observation, there were 157 deaths as a result of AMI, with a death rate of 7.06 per 1000 person-years. Mortality rates were higher in older age groups and in men. After adjustment for age, sex, race, and disease duration, the risk of AMI declined in successive incidence years (relative risk, 0.94; 95% CI, 0.92 to 0.96). Patients with rheumatoid arthritis incident after 1990 did not have excess AMI mortality compared with general population. Declines in mortality trends were observed in successive birth cohorts as well. CONCLUSIONS: Mortality as a result of AMI among patients with rheumatoid arthritis has declined over time. | |
| 12756895 | [Approximation to the cost of pharmacological treatment of rheumatoid arthritis in Spain]. | 2003 Mar | OBJECTIVE: To study the direct cost derived of utilization of pharmaceutical compounds in the treatment of rheumatoid arthritis(RA). MATERIAL AND METHODS: A prospective study with 150 patients (125 women/25 men) suffered of RA was carry out in Galicia-Spain public hospital. The mean age was 60.2 years, with a mean lengthy of disease of 11.2 years (1-53); the 64.4% come from rural areas. A personal interview was made with a complete registry of all data: demographic, activity score (ESR, Swollen joints), radiological status, functional class (ACR), extrarticular manifestations and co-morbid diseases. Such data was accomplished with all the medications employees with a calculation of monthly or annual cost for the different therapeutic groups and a final total cost. The statistical study was made with Excel's (Microsoft) and the Analysis Tool Pack. RESULTS: The 53% of patients was in functional class I and 52% in radiological stage I or II (Steinbrocker) whereas 16 patients was considered in remission. Non-steroideal ant-inflammatory drugs (NSAID) were used in the 82.7% of patients with a monthly cost of 12.71 [symbol: see text] (1.10-80). Corticosteroids at low doses were used in 90.7% with a monthly cost of 5.17 [symbol: see text] (1.24-33.7). The Disease Modifying Anti-rheumatic Drugs (DMARD) was used in 94% of cases, the most common methotrexate and association of two or more in 21%. The mean monthly cost for a single DMARD was 3.63 [symbol: see text] and for two, 13.75 [symbol: see text]. Gastroprotection and therapy for co-morbid diseases was employee in 80% and 95% of cases, with a monthly cost of 36.9 [symbol: see text] and year cost of 568.6 [symbol: see text], respectively. The study included 23 patients under treatment with anti-TNF therapy with a monthly mean cost of 933.8 [symbol: see text]. For pharmaceuticals exclusively for RA, annual cost was 342.8 [symbol: see text] excluding anti-TNF therapy, but with wide variation (6.4-2.910 [symbol: see text]). If we include all patients with anti-TNF therapy, gastro-protection and co-morbid situations in a calculation, the mean cost was 2.587 [symbol: see text] year. The most important cost was found in patients with 50-70 years-old and existing a good correlation between the final burden and use of medications for co-morbid conditions, gastro-protection, use of anti-TNF, age, lengthy of disease between 5-10 years and number of swollen joints, but not radiological stage. CONCLUSIONS: The economic burden for pharmaceuticals used in RA is very variable depending of some variables, including the proper disease and other related conditions. The most important cost occur in case of use of anti-TNF therapy. In the most frequent conditions, gastro-protection and therapy for co-morbid diseases lead the 62% of total annual burden, followed by the use of DMARD and in a minor load, the NSAIDs and corticosteroids. | |
| 12759297 | In vitro growth rate of fibroblast-like synovial cells is reduced by methotrexate treatmen | 2003 Jun | BACKGROUND: Fibroblast-like synovial cells (FLS) can be cultured and expanded in vitro in monolayer. Little is known about the growth characteristics of FLS derived from different patients. OBJECTIVE: To study FLS cultures, with particular attention to differences in growth rate of FLS from patients with rheumatoid arthritis (RA) and from other arthritic patients. Additionally, to analyse the influence of methotrexate (MTX) treatment, patient age, and disease duration on FLS growth characteristics. MATERIALS AND METHODS: FLS were isolated from needle arthroscopy biopsy specimens. Twenty four patients (11 RA, 8 spondyloarthropathy, 1 osteoarthritis, and 4 undifferentiated arthritis) were studied. FLS population doubling time was determined between passage 2 and passage 5. Differences in population doubling time between RA and non-RA FLS and between FLS from patients receiving MTX and those not receiving this drug were analysed. In addition, possible correlations between FLS population doubling time and patient age or disease duration were examined. RESULTS: In vitro monolayer FLS cultures from needle arthroscopy biopsy specimens showed linear growth characteristics. Cell growth rate was not correlated with type of disease. Cells from patients undergoing treatment with MTX showed a longer population doubling time than FLS from patients not receiving this drug (Mann-Whitney test, p<0.05). No correlation was found with patient age or disease duration. CONCLUSION: The results suggest that FLS growth in monolayer is not dependent on the disease affecting the joint. MTX treatment, however, was more relevant in determining FLS growth rate. | |
| 14969076 | The Early Rheumatoid Arthritis (ERA) trial comparing the efficacy and safety of etanercept | 2003 Sep | The Early Rheumatoid Arthritis (ERA) trial compared monotherapy with etanercept or methotrexate in patients with early erosive rheumatoid arthritis. Over the initial period of 12, and subsequently 24, months both treatments were associated with a profound reduction in radiographic progression of joint damage, as well as a reduction in signs and symptoms of disease. Etanercept showed slight superiority to methotrexate in reducing subsequent radiographic erosions and in the rapidity of the clinical response. Both therapies proved to be safe and well tolerated and, importantly, the relative safety and tolerance of a rapidly escalated dosing regimen for methotrexate was demonstrated. In summary, early aggressive treatment of RA is associated with clinical and radiographic benefit that can be demonstrated after a relatively short period of treatment. |