BackgroundNetwork PR-LR is designed to improve the management of patients with rheumatoid arthritis (RA) in the Languedoc Roussillon (France). It conducts training activities, information for patients and health professionals on rheumatoid arthritis. It now has 1,263 patients. There is an anonymized medical records and computerized for each patient which allows regular monitoring.ObjectivesCompare the consumption of medical procedures between patients in or those outside to the network system.MethodsTo study the data from RA patients, we asked to the regional health insurance company (RHIC) a list of patients with medical and economic information usable. We gave the health insurance list of patient care within the network. The RHIC has extracted about two years (June 2009-July 2011) a database containing anonymised patient outside the network PR-LR. Once we got the information from the RHIC, we analyzed several criteria: per diem reimbursement, visits to the doctor, number of visits to specialists, many acts of biology and radiology. Other criteria have not yet been exploited due to lack of data: type of treatment (use of corticosteroids, NSAIDs, DMARDs or biological agents), number of hospitalizations, surgical procedures. For comparison of common variables, we used a Chi2 test.ResultsOver the period studied, we obtained 5936 non-network patients versus 465 patients in the network and living in the Languedoc Roussillon. Non-network patients (N=5936) were a mean age of 61.86 years (SD 15.18), duration symptoms RA of 6 years (SD 3.8). There are 1631 men and 4305 women. The sex male/female ratio is 0.37. Patients Network (N=465) had a mean age of 62.49 years (SD 14.71), an unknown length of RA. There are 99 men and 306 women. The sex male/female ratio is 0.27. There is a significant difference between the 2 groups. In the Network patients group, we observed: –less diem reimbursement: 13.55 (71.32) vs 22.71 (91.13) p=0.0088 –Fewer visits to the doctor: 10.73 (10.81) vs 13.66 (11.36) p=0.00001 –No difference in the number of specialist consultations: 7.34 (7.62) vs 7.52 (7.11) p=0.1761 –No differences in the number of acts of biology but more likely because follow-up is better: 47.11 (41.16) vs 41.88 (37.06) p=0, 0532 –Less X-ray procedures: 6.78 (6.97) vs 8.55 (8.35) p=0.00001 –Less Radiographs of hands for better monitoring: 0.37 (0.78) vs 0.55 (1.09) p=0.0081. Warning of the date of the last ray is given to the physician –No differences in the number of radiographs of the feet: 0.55 (1.04) vs 0.49 (0.99) p=0.1897ConclusionsThis study has many limitations but shows for the first time a benefit of a network of care on the treatment of RA patients. Better monitoring through the computer interface allows us a better tight control of the patient and a profit on medical consumption shown by the decrease in visits to the doctor, acts of x-rays and the number of per diem reimbursement.Disclosure of InterestNone Declared

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 (lambda), 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 euro, respectively. Among the direct costs, infliximab accounts for 21,182 euro 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, lambda is 9841 euro (18,593 for all HAQ). When it is expressed in QALYs, also for severe HAQ, lambda > 100,000 euro. 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 treatment.

Examiner la consommation de soins et la qualité de vie (utilité) sur un échantillon de patients présentant tout l’éventail des caractéristiques de la maladie, des modalités de prise en charge et de leur répartition géographique. Les informations sur la démographie, les paramètres de la maladie, la capacité à travailler et la consommation de ressources (au cours du dernier mois, ou des trois ou 12 derniers mois selon les cas) ont été collectées par un sondage anonyme envoyé par courrier à tous les membres d’une association nationale de patients (ANDAR). Les résultats sont présentés pour l’échantillon et par niveau de capacité fonctionnelle et sont exprimés en euros (€) pour l’année 2005. Mille quatre cent quatre-vingt-sept patients ont été inclus dans l’analyse (taux de réponse 49 %). L’âge moyen était de 62,7 ans et 83,5 % des personnes ayant répondu étaient des femmes. La durée moyenne de la maladie était de 18 ans ; la moyenne du score du health assessment questionnaire (HAQ) était de 1,42 ; la fatigue et la douleur étaient respectivement classées à 5,6 et à 4,8 sur une échelle de 0 à 10. Parmi les patients de moins de 60 ans, 34 % ont pris leur retraite prématurément à cause de la PR, et seulement 15 % des patients avec un HAQ de 2 ou plus travaillaient. La perte de productivité a été estimée à 5 076 €, dont le paiement des indemnités couvrait 1944 €. Les coûts des soins de santé directs étaient de 11 757 € du point de vue de la société et de 9 216 € selon l’Assurance maladie. Les coûts non médicaux directs (incluant les soins informels) étaient, respectivement, de 4857 et 136 €. Les coûts pour la société passaient de 9 400 € dans le cas d’une maladie modérée à 40 700 € en cas de pathologie sévère, et pour les services publics de 6000 à 19 000 €. L’utilité diminuait simultanément de 0,80 à 0,06. Cette étude confirme les conclusions générales obtenues au cours d’autres études dans différents pays et apporte une première estimation des coûts globaux selon le degré de sévérité de la maladie en France.

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 12 months 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 (sic)2005.Results: 1487 patients were included in the analysis (response rate 49%). Mean age was 62.7 years and 83.5% of respondents were female. Mean disease duration was 18 years; 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 60 years, 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 (SIC)5076, of which indemnity payments covered (sic)1944. Direct health care costs were (sic)11,757 in the societal perspective and (sic)9216 in the perspective of the national health insurance. Direct non-medical costs (including informal care) were (sic)4857 and (sic)136 respectively. Costs to society increased from (sic)9400 in mild disease to (sic)40,700 in severe disease, and to public payers from (sic)6000 to (sic)19,000. 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. (c) 2008 Elsevier Masson SAS. All rights reserved.

General practitioners’ perception of the discomfort their patients experience because of corticosteroid-induced adverse events is unknown.An observational epidemiological study was conducted in September 2007. Eight hundred and sixty general practitioners belonging to the réseau Sentinelles® were asked to complete an electronical questionnaire. The questionnaire aimed to assess their perception of discomfort induced by adverse events induced by a long-term (i.e., ≥ 3 months) corticosteroid therapy among their patients. Results were compared with the declaration made by 115 long-term corticosteroid treated patients followed in an internal medicine department.Two hundred and ninety-three general practitioners responded to the questionnaire (response rate: 34%). They were predominantly male (87%). Forty-eight percent of them reported 400 to 600 monthly visits. The mean length of corticosteroid therapy for patients was 44 ± 38 months and the mean daily dosage was 15 ± 14 mg. They suffered mainly from lupus erythematosus (33%) or giant cell arteritis (15%). The adverse events considered to be the most disturbing by patients were lipodystrophy (25%), followed by weight gain (18%) and neuropsychiatric complaints (16%). Physicians widely overestimated the discomfort caused by weight gain cited as the most disturbing adverse event by 59% of them and underestimated that induced by mood disorders cited as the most disturbing by only 3% of them.The discomfort caused by corticosteroid-induced neuropsychiatric adverse events are underestimated by general practitioners.On ne sait pas si la perception qu’ont les médecins généralistes de la gêne induite par les effets indésirables d’une corticothérapie systémique prolongée (≥ 3 mois) est superposable à celle des patients.En septembre 2007, une enquête transversale a été menée à l’aide d’un questionnaire électronique adressé par courriel aux 860 médecins généralistes membres du réseau Sentinelles®. Le questionnaire électronique comportait des questions à choix simple ou à choix multiples concernant notamment leur perception de la gêne induite par les effets indésirables d’une corticothérapie systémique prolongée. Ces résultats étaient comparés aux déclarations de 115 patients recevant au long cours une corticothérapie orale et suivis dans un service de médecine interne.Deux cent quatre-vingt-treize médecins (34 %) ont répondu au questionnaire. Il s’agissait essentiellement d’hommes (87 %) voyant pour 48 % d’entre eux 400 à 600 patients par mois. Les 115 patients interrogés recevaient en moyenne des corticoïdes depuis 44 ± 38 mois, prescrits à la posologie moyenne de 15 ± 14 mg/j, le plus souvent pour un lupus (33 %) ou une maladie de Horton (15 %). L’effet indésirable rapporté par les patients comme étant le plus gênant dans la vie quotidienne était la lipodystrophie (25 %) suivi de la prise de poids (18 %) et des troubles neuropsychiatriques (16 %). La gêne induite par la prise de poids était surestimée par les praticiens (59 % déclarant cet effet indésirable comme le plus gênant) alors qu’ils sous-estimaient la gêne induite par les troubles neuropsychiatriques (citée par seulement 3 % des praticiens comme l’effet indésirable le plus gênant).La gêne induite par les troubles neuropsychiatriques cortico-induits est sous-estimée par les médecins généralistes.

The progress of immunopathology allowed the development of targeted drugs or biotherapies. Among them, monoclonal antibodies against T or B lymphocytes or against a cytokine are reported. Monoclonal anti-TNF antibodies are a major therapeutic advance because they can stop the clinical, biological and radiographic evolution of rheumatoid arthritis (RA). Monoclonal anti-CD20 lymphocytes give promising results; they are able to induce prolonged remissions. Monoclonal anti-IL6 receptors are currently being evaluated. They are efficacious in adult RA and in Still's disease. Because of the infectious risk linked to these drugs, the ratio benefit/risk must be carefully evaluated before the prescription of a biotherapy.

Monoclonal antibodies in the treatment of rheumatoid arthritis: toward a therapeutic revolution. The progress of immunopathology allowed the development of targeted drugs or biotherapies. Among them, monoclonal antibodies against T or B lymphocytes or against a cytokine are reported. Monoclonal anti-TNF antibodies are a major therapeutic advance because they can stop the clinical, biological and radiographic evolution of rheumatoid arthritis (RA). Monoclonal anti-CD20 lymphocytes give promising results; they are able to induce prolonged remissions. Monoclonal anti-IL6 receptors are currently being evaluated. They are efficacious in adult RA and in Still's disease. Because of the infectious risk linked to these drugs, the ratio benefit/risk must be carefully evaluated before the prescription of a biotherapy.

OBJECTIVES:To develop recommendations for the physical and laboratory-test follow-up of patients with rheumatoid arthritis (RA) seen in everyday practice, using evidence from the literature, supplemented with expert opinion when needed.METHODS:A scientific committee selected 7-10 questions using the Delphi consensus procedure. Evidence-based responses to each question were sought in the literature and were then used by a panel to develop recommendations. To fill in gaps in knowledge from the literature, the panelists relied on their personal opinion.RESULTS:The seven questions dealt with the physical and laboratory-test follow-up of RA and the factors predicting disease severity. The literature review identified 799 articles whose title and abstract suggested relevance to the study. Elimination of articles that provided no data on the study topic left 128 original articles. The panel developed seven recommendations, one for each question, which were accepted by consensus.CONCLUSION:Recommendations about the physical and laboratory-test follow-up of patients with RA seen in everyday practice were developed. Because they constitute an objective foundation built by consensus among experts, should improve the uniformity and quality of care provided to RA patients in everyday practice.

OBJECTIVES:To develop recommendations for the information and education of patients with rheumatoid arthritis (RA) seen in everyday practice, using evidence from the literature, supplemented with expert opinion when needed.METHODS:A scientific committee developed eight questions using the Delphi consensus procedure. A task force reviewed the literature for answers to these questions, using the PubMed Medline database (1980-2004) and the 2002-2004 databases of the annual meetings held by the French Society for Rheumatology (SFR), the European League Against Rheumatism (EULAR), and the American College of Rheumatology (ACR); the indexing terms for the search were rheumatoid, arthritis, patient, education, information, knowledge, general practitioner, family doctor, and continuing medical education. Only articles in French or English were included. A panel of rheumatologists used the evidence thus compiled to develop recommendations for each question; gaps in evidence were filled by calling on the panelists' expert opinion. For each recommendation, the level of evidence and extent of agreement among panelists were specified.RESULTS:There were four general questions about the objectives, supports, and mode of delivery (group or one-on-one) of patient information and education, as well as on evaluating knowledge, and four specific questions on program content. The search identified 1235 articles; 144 were selected on the title and 118 of those on the abstract. Three abstracts presented at meetings were also kept. The evidence from the literature was presented to the panelists during interactive workshops. The panelists then developed eight recommendations, all of which were grade D because no published studies specifically addressed everyday clinical practice. Agreement among panelists ranged across recommendations from 85.7% to 100%.CONCLUSION:Recommendations about educating and informing patients with RA in everyday practice were developed. They should increase practice uniformity and ultimately optimize the management of patients with RA.

OBJECTIVES:To develop French evidence-based recommendations for the structural evaluation of rheumatoid arthritis (RA) in everyday practice. METHODS:A scientific committee selected 10 questions using the Delphi consensus procedure. Evidence-based responses to each question were sought by searching the PubMed and Ovid databases and the abstract databases for the 2002, 2003, and 2004 annual meetings of the French Society for Rheumatology, the EULAR, and the American College of Rheumatology. The following indexing terms were used: rheumatoid arthritis, arthritis, patient, diagnostic imaging, radiography, joint, erosion, and joint space width. All articles published in French or English prior to May 2004 were identified. The evidence from these articles was reported to a panel of 77 rheumatologists working in hospital or office practice. The panel developed detailed recommendations, filling gaps in evidence with their expert opinion. The strength of each recommendation was determined. RESULTS:The 10 questions probed the structural evaluation of RA by plain radiography, magnetic resonance imaging (MRI), and ultrasonography, both for diagnostic and monitoring purposes. The literature search retrieved 673 publications, of which 166 were selected and reviewed. The panel developed 10 recommendations, one for each question, which were accepted by consensus. CONCLUSION:Recommendations relative to the diagnosis or monitoring of structural involvement in patients with RA in everyday practice were developed. They should help to improve practice uniformity and, ultimately, to improve the management of RA.

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.

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 -2.27 (-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.

Proposer des recommandations pour l'évaluation clinique et biologique de la polyarthrite rhumatoïde (PR) en pratique quotidienne, selon la méthodologie de la médecine fondée sur les niveaux de preuve (Evidence Based Medicine) (EBM) et l'opinion d'experts. L'étude s'est décomposée en trois temps :o1. détermination de sept à dix questions, base de la rédaction des recommandations, par un comité scientifique selon la méthode Delphi2. recherche d'éléments de réponse type EBM par une revue de la littérature ;3. développement de recommandations par un comité d'experts à partir de ces éléments. 1. détermination de sept à dix questions, base de la rédaction des recommandations, par un comité scientifique selon la méthode Delphi 2. recherche d'éléments de réponse type EBM par une revue de la littérature ; 3. développement de recommandations par un comité d'experts à partir de ces éléments. o1. Les sept questions sélectionnées portaient sur l'évaluation clinique et biologique de la PR, ainsi que sur les facteurs prédictifs de sévérité de la maladie.2. La revue de la littérature a permis de sélectionner 799 articles sur le titre et le résumé. Les publications dont l'analyse ne concernait pas l'évaluation clinique et/ou biologique ont été éliminées. Au final, 128 articles originaux ont été inclus dans l'analyse globale.3. Sept recommandations relatives à l'évaluation clinique et biologique de la PR ont été élaborées à partir des résultats de la revuede la littérature et de l'opinion d'experts. Ces recommandations ont été validées par un vote final de l'ensemble des participants. 1. Les sept questions sélectionnées portaient sur l'évaluation clinique et biologique de la PR, ainsi que sur les facteurs prédictifs de sévérité de la maladie. 2. La revue de la littérature a permis de sélectionner 799 articles sur le titre et le résumé. Les publications dont l'analyse ne concernait pas l'évaluation clinique et/ou biologique ont été éliminées. Au final, 128 articles originaux ont été inclus dans l'analyse globale. 3. Sept recommandations relatives à l'évaluation clinique et biologique de la PR ont été élaborées à partir des résultats de la revuede la littérature et de l'opinion d'experts. Ces recommandations ont été validées par un vote final de l'ensemble des participants. Des recommandations relatives au suivi clinique et biologique de la PR ont été développées. Elles apportent un élémentobjectif et consensuel de réponse à des questions cliniques-clés pour une uniformisation et une optimisation de la prise en charge de la PR en partique clinique quotidienne.