Medico-economic evaluation of infliximab in rheumatoid arthritis—prospective French study of a cohort of 635 patients monitored for two years

Objectives. To perform, in real conditions of prescription, the medico-economic evaluation of infliximab in severe RA. Methods. A cost-effectiveness analysis of the annual costs was done with a comparison between the previous and the following year under infliximab. The effectiveness, determined from the HAQ, was expressed in clinically significant units and in quality-adjusted life years (QALYs). The incremental net benefit (INB), defined as willingness to pay (λ), was used to express the results. Results. A cohort of 635 patients was formed. Before the use of infliximab, after 1 and 2 years, the mean annual cost per patient for the care of RA was €9832, 27 723 and 46 704, respectively. Among the direct costs, infliximab accounts for €21 182 for the first year. The distribution of the different costs was similar after 2 years. By using the INB, the difference before and after 1 year under infliximab is significant, on average by 1.86 (s.e.m. = 0.76) when the effectiveness is expressed in clinically significant units. For severe HAQ, λ is €9841 (18 593 for all HAQ). When it is expressed in QALYs, also for severe HAQ, λ >€100 000. This can be explained by a short follow-up although severe complication of RA appears later. Conclusion. An evaluation of the more long-term costs is required in order to determine whether there are any full economic benefits with this treatmen

Transcriptional profiles discriminate bone marrow-derived and synovium-derived mesenchymal stem cells

Previous studies have reported that mesenchymal stem cells (MSC) may be isolated from the synovial membrane by the same protocol as that used for synovial fibroblast cultivation, suggesting that MSC correspond to a subset of the adherent cell population, as MSC from the stromal compartment of the bone marrow (BM). The aims of the present study were, first, to better characterize the MSC derived from the synovial membrane and, second, to compare systematically, in parallel, the MSC-containing cell populations isolated from BM and those derived from the synovium, using quantitative assays. Fluorescent-activated cell sorting analysis revealed that both populations were negative for CD14, CD34 and CD45 expression and that both displayed equal levels of CD44, CD73, CD90 and CD105, a phenotype currently known to be characteristic of BM-MSC. Comparable with BM-MSC, such MSC-like cells isolated from the synovial membrane were shown for the first time to suppress the T-cell response in a mixed lymphocyte reaction, and to express the enzyme indoleamine 2,3-dioxygenase activity to the same extent as BM-MSC, which is a possible mediator of this suppressive activity. Using quantitative RT-PCR these data show that MSC-like cells from the synovium and BM may be induced to chondrogenic differentiation and, to a lesser extent, to osteogenic differentiation, but the osteogenic capacities of the synovium-derived MSC were significantly reduced based on the expression of the markers tested (collagen type II and aggrecan or alkaline phosphatase and osteocalcin, respectively). Transcription profiles, determined with the Atlas Human Cytokine/Receptor Array, revealed discrimination between the MSC-like cells from the synovial membrane and the BM-MSC by 46 of 268 genes. In particular, activin A was shown to be one major upregulated factor, highly secreted by BM-MSC. Whether this reflects a different cellular phenotype, a different amount of MSC in the synovium-derived population compared with BM-MSC adherent cell populations or the impact of a different microenvironment remains to be determined. In conclusion, although the BM-derived and synovium-derived MSC shared similar phenotypic and functional properties, both their differentiation capacities and transcriptional profiles permit one to discriminate the cell populations according to their tissue origin

Traitement de la polyarthrite rhumatoïde par Etanercept (à propos d'une cohorte de 103 cas)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Polyarthrite rhumatoïde (traitements actuels et thérapeutiques d'avenir)

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Evaluation socio-économique de 63 cas incidents de polyarthrite rhumatoïde, ayant bénéficié d'une prise en charge pluridisciplinaire et suivis en milieu hospitalier pendant deux ans

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Intracytoplasmic Th1 and Th2 cytokines in rheumatoid arthritis blood and synovial tissue

In rheumatoid arthritis (RA), T cells have been proposed either as a main actor or as an epiphenomenon in such a primarily synoviocyte-driven disease. A major issue remains the remarkable paradox between the T cell infiltrate and the relative failure to detect definite markers of their activity. To determine the Th1/Th2 cytokine profile in RA synovium, we used a single cell flow cytometric assay for interleukin-2 (IL-2), interferon-γ (FN-γ), IL-4 and IL-10 in paired peripheral blood (PB) and synovial tissue (ST) lymphocytes from RA and osteoarthritis (OA) patients and PB lymphocytes from healthy controls. Cytokines were undetectable in unstimulated PB and ST lymphocytes. More stimulated PB arm ST CD4+ lymphocytes produced IFN-γ than IL-4, for all individuals tested. RA PB CD4+ lymphocytes showed the same Th1 cytokine pattern as normal controls. No increase of such a Th1 profile was observed for ST lymphocytes. A specific recruitment of T CD4+ lymphocytes in the rheumatoid inflamed synovium could not be concluded on the basis of these results

Disease status, costs and quality of life of patients with rheumatoid arthritis in France: The ECO-PR Study.

OBJECTIVE: To investigate resource consumption and quality of life (utility) in a sample of patients covering the full spectrum of the disease, modalities of patient management and geographic areas. METHODS: Information on demographics, disease parameters, work capacity and resource consumption (in the past 1, 3 or 12months depending on the resource) was collected in an anonymous mail survey from all members of a national patient association (ANDAR). Results are presented for the sample and by level of functional capacity, in euro2005. RESULTS: 1487 patients were included in the analysis (response rate 49%). Mean age was 62.7years and 83.5% of respondents were female. Mean disease duration was 18years; mean HAQ was 1.42; fatigue and pain ranked 5.6 and 4.8 on a scale between 0 and 10, respectively. Of patients below 60years, 34% had taken early retirement due to RA, and only 15% of patients with a HAQ of 2 or higher were working. Productivity losses were estimated at euro5076, of which indemnity payments covered euro1944. Direct health care costs were euro11,757 in the societal perspective and euro9216 in the perspective of the national health insurance. Direct non-medical costs (including informal care) were euro4857 and euro136 respectively. Costs to society increased from euro9400 in mild disease to euro40,700 in severe disease, and to public payers from euro6000 to euro19,000. Utility decreased simultaneously from 0.80 to 0.06. CONCLUSION: The study confirms overall findings in other studies in other countries, and provides the first estimate of all costs by disease severity in France

Polymorphism of HLA-DMA and DMB Alleles in Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organs that is characterized by the production of various antibodies against nuclear, cytoplasmic, and cell surface antigens. The expression of SLE is influenced by environmental factors and genetic predisposition 1 . Case-control studies have shown that HLA-DR2 and DR3 alleles are associated with SLE 2-5 . HLA class II regions also contain HLA-DMA and HLA-DMB genes. These 2 genes encode respectively for α and ß glycoproteins that make up the HLA-DM heterodimer involved in class II-dependent antigen presentation. To date, 4 DMAalleles and 6 DMB alleles have been described MATERIALAND METHODS Patients and controls. Seventy-three SLE patients (68 women, 5 men, median age 35 yrs, range 12-81) were examined. SLE was diagnosed by 2 rheumatologists according to the American College of Rheumatology (ACR) 1982 revised criteria 14 . All patients were of Caucasian origin. Blood was collected at the Rheumatology Department of the University Hospital of Montpellier. Two unrelated control populations were used in this study. All were healthy volunteer bone marrow donors recruited in the Montpellier area. One group consisted of 147 individuals randomly selected and typed for HLA-DR and HLA-DM genes. To determine if the association between SLE and certain HLA-DM alleles resulted from a direct influence of the DM genes or an indirect influence through linkage disequilibrium with alleles of the DRB1 locus, a second group of controls was defined. This group was composed of 86 individuals carrying DRB1*02 or DRB1*03, the SLE-associated HLA-DRB1 alleles. Methods. Genomic DNAwas extracted from peripheral blood mononuclear cells according to the classic salting-out procedure. DRB1 alleles were typed as describe

Objective and subjective sleep disturbances in patients with rheumatoid arthritis. A reappraisal.

OBJECTIVE. To assess objective and subjective evidence of sleep disturbances in patients with rheumatoid arthritis (RA) and to examine correlations between parameters of inflammatory activity and sleep pathology. METHODS. Nineteen RA patients and 19 age-matched healthy control subjects underwent all-night polysomnography on 2 consecutive nights. RA patients were also evaluated for daytime sleepiness by mean sleep latency test and responded to a self-report questionnaire on their first night. RESULTS. Whereas normal sleep architecture is conserved in RA, we confirmed former findings of severe sleep fragmentation and an enhanced presence of primary sleep disorders. No correlation exists between RA activity and the sleep disorders. Subjective assessment was not consistent with the objective evidence of sleep disruption, unlike the findings in patients with fibrositis. CONCLUSION. Sleep is severely disturbed in patients with RA, regardless of the inflammatory disease activity. The specificity of the sleep disorders assessed needs confirmation, as does specific sleep therapy for these patients