Rheumatoid Arthritis: Fautrel B

Pham T, Fautrel B, Gottenberg JE, Goupille P, Hachulla E, Masson C, Morel J, Mouthon L, Saraux A, Schaeverbeke T, Wendling D, Mariette X, Sibilia, Anonymous00011. · No affiliation provided · Joint Bone Spine. · Pubmed #18708020 No free full text.

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Fautrel B, Pham T, Mouterde G, Le Loët X, Goupille P, Guillemin F, Ravaud P, Cantagrel A, Dougados M, Puéchal X, Sibilia J, Soubrier M, Mariette X, Combe B, Anonymous00061, Anonymous00062. · Pierre and Marie Curie University - Paris VI, UFR de Médecine, France. · Joint Bone Spine. · Pubmed #18037319 No free full text.

Abstract: OBJECTIVES: To update French Society for Rheumatology guidelines regarding the use of TNFalpha antagonists for treating patients with rheumatoid arthritis (RA). METHODS: Existing guidelines were updated using the AGREE instrument. Items that required updating were selected by a task force, the relevant literature was critically appraised, and new wording was suggested by a limited committee of experts then validated by the task force and subsequently by a panel of external reviewers. The three-topic structure of the recommendations (indication, initiation, and adjustment) and the final algorithm format were maintained. RESULTS: Of the 12 items, five were selected for updating; one pertained to the indication for treatment with TNFalpha antagonists, two to treatment initiation, and two to treatment adjustment. Of the four initially recommended criteria for determining that TNFalpha antagonist therapy is indicated, the first three were left unchanged (confirmed diagnosis of RA; active disease for more than 1month with objective evidence of inflammation or progressive structural damage, or dependency on glucocorticoid therapy, or progressive radiographic damage; and failure to respond adequately to methotrexate - or another agent when methotrexate is contraindicated - in the optimal tolerated dosage). The fourth and last criterion was modified as follows: co-morbidities should be evaluated in order to distinguish absolute contraindications from relative contraindications that require referral to a specialist. Of the four initial recommendations about TNFalpha antagonist initiation, the first and fourth were left unchanged (a workup should be performed prior to treatment initiation, and the patient should receive regular standardized follow-up); the second and third recommendations were modified as follows: there is no evidence that one TNFalpha antagonist is more effective than the others, and concomitant methotrexate therapy is generally advisable, regardless of the TNFalpha antagonist used. Of the four recommendations about treatment adjustment, the first two were modified as follows: the goal of treatment is to achieve the EULAR response criteria or better; and in non-responders, the dosage or dosing interval can be modified when infliximab is used, methotrexate should be added when the TNFalpha antagonist is used alone, and in all other situations the patient should be switched to a different TNFalpha antagonist. The other two recommendations about treatment adjustment were left unchanged (patients who fail to tolerate one TNFalpha antagonist can be switched to another TNFalpha antagonist if allowed by the nature of the adverse event; and when a remission is achieved, reduction or discontinuation of symptomatic drugs - most notably glucocorticoids - is appropriate, followed in the event of a prolonged remission by changes in the dosage and/or dosing interval of the TNFalpha antagonist or concomitant disease-modifying drug). CONCLUSION: These recommendations are designed to help practitioners optimize the use of TNFalpha antagonists in patients with RA seen in everyday practice. They do not constitute regulations.

Binard A, Devauchelle-Pensec V, Fautrel B, Jousse S, Youinou P, Saraux A. · No affiliation provided · Clin Exp Rheumatol. · Pubmed #17417982 No free full text.

This publication has no abstract.

Fautrel B. · No affiliation provided · Joint Bone Spine. · Pubmed #12184429 No free full text.

This publication has no abstract.

Fautrel B. · Pierre & Marie Curie-Paris VI University/Paris Universitas, Department of Rheumatology, Pitié-Salpêtrière Hospital, 83 boulevard de l'Hôpital, 75651 Paris, Cedex 13, France. · Best Pract Res Clin Rheumatol. · Pubmed #19028363 No free full text.

Abstract: Adult-onset Still disease (AOSD) is an uncommon inflammatory condition of unknown origin typically characterized by four main (cardinal) symptoms: spiking fever > or =39 degrees C, arthralgia or arthritis, skin rash and hyperleucocytosis (> or =10,000 cells/mm3) with neutrophils > or =80%. As many other manifestations are possible, diagnosis is potentially challenging. Determination of the total and glycosylated ferritin levels, although not pathognomonic, can help in diagnosis. The disease evolution of AOSD can be monocyclic, polycyclic or chronic. In chronic disease, joint involvement is often predominant and erosions are noted in one-third of patients. No prognostic factors have been identified to date. Therapeutic strategies are from observational data. Corticosteroids are usually the first-line treatment. With inadequate response to corticosteroids, methotrexate appears the best choice to control disease activity and allow for tapering of steroid use. For refractory disease, biological therapy with agents blocking interleukin-1 (anakinra) and then those blocking interleukin-6 (tocilizumab) seem the most promising.

Fautrel B, Pham T, Gossec L, Combe B, Flipo RM, Goupille P, Le Loët X, Mariette X, Puéchal X, Wendling D, Schaeverbeke T, Sibilia J, Sany J, Dougados M. · Service de rhumatologie, groupe hospitalier Pitié-Salpêtrière, Paris, France. · Joint Bone Spine. · Pubmed #15797498 No free full text.

Abstract: 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.

Fanet-Goguet M, Martin S, Fernandez C, Fautrel B, Bourgeois P. · Service de Rhumatologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Therapie. · Pubmed #15559549 No free full text.

Abstract: Tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 are major regulators of inflammation. TNFalpha inhibitors have been shown to be effective in treating some inflammatory diseases such as rheumatoid arthritis. TNFalpha inhibitors include soluble receptor antagonists (etanercept) and monoclonal antibodies (infliximab, adalimumab). IL-1 inhibitors (anakinra) were also developed, used in therapeutics and licensed in France. TNFalpha inhibitors can be added to background regimens of methotrexate in second-line treatments. Etanercept and adalimumab can be administered alone, especially to patients who have experienced methotrexate toxicity or who do not show clinical and/or radiological improvement. The use of these new agents may optimise rheumatoid arthritis treatment and delay disease progression, particularly when first-line treatments are disappointing. This paper reviews recent data on biological therapies for rheumatoid arthritis: tolerance and their ability to modify the course of disease and prevent radiological damage.

Fautrel B, Guillemin F. · Rheumatology Unit, Pitié-Salpêtrière Hospital, Paris, France. · Curr Opin Rheumatol. · Pubmed #11845016 No free full text.

Abstract: Knowledge about the economic burden of rheumatic diseases has progressed during recent years. In addition to the increasing number of studies published, the Economics Working Group of the Outcome Measures in Rheumatoid Arthritis Clinical Trial (OMERACT) Conference has produced substantial work to improve methodological standards for the economic evaluation of rheumatic diseases. Some of their preliminary results are presented in this review. Recent data have confirmed two main conclusions of previous studies: the total economic burden of rheumatic diseases is often more substantial than other chronic conditions, including cardiovascular diseases and cancer; and the impact of the disability caused by musculoskeletal diseases is significant on both direct (long-term care in osteoporosis for example) and indirect costs (productivity loss in chronic patients). Besides that, cost-effectiveness studies have provided valid information to improve disease management, especially for patients with rheumatoid arthritis or chronic low back pain.

Fautrel B, Cherin P. · Service de rhumatologie, hôpital de la Pitié-Salpêtrière, Paris, France. · Rev Med Interne. · Pubmed #11075396 No free full text.

Abstract: INTRODUCTION: The pathophysiological interest of tumor necrosis factor-alpha (TNF-alpha) has been recently reported in inflammatory and infectious diseases. Thus, TNF-alpha blockade has become a new field of therapeutical research. CURRENT KNOWLEDGE AND KEY POINTS: Several biological agents specifically directed against TNF-alpha are available: anti-TNF-alpha monoclonal antibodies on the one hand--either mainly murine sequence (cA2), partially humanized (CDP 571) or fully human (D2E7)--and TNF-alpha soluble receptors on the other hand (lenercept or etanercept). The first clinical studies reveal interesting results. In rheumatoid arthritis (cA2, etanercept), these molecules may be used either alone or in synergistic combination with methotrexate. They produce a significant response compared to placebo or methotrexate alone, without loss of efficacy in medium-term treatment. In Crohn's disease (cA2 CDP571), they reduce significantly the activity of the disease, compared to placebo, and cA2 makes it possible to accelerate closure of the fistulas. The studies of severe sepsis did not reveal a significant efficacy, however, and only one study has been published on malignant disease, with a possible interesting effect. Even if these medications are usually well tolerated, the frequency of infections is slightly increased. The development of anti-DNA antibodies has also been reported, but drug-induced lupus is highly unusual. FUTURE PROSPECTS AND PROJECTS: Further studies will define the place of anti-TNF-alpha biological agents among the other available treatments of rheumatoid arthritis and Crohn's disease. Because of their high cost, these drugs will probably be limited to patients with active inflammatory disease despite more conventional treatments.

Fautrel B, Bourgeois P. · Service de Rhumatologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Drugs. · Pubmed #10841067 No free full text.

Abstract: Of all rheumatic diseases, osteoarthritis (OA) and rheumatoid arthritis (RA) are the most frequently occurring. Although they differ in pathophysiology and the molecular mechanisms responsible for the destruction of cartilage (since RA is an inflammatory disease and OA is not), there are, however, a certain number of similarities and common pathways in the inflammatory processes of both diseases: mild inflammatory phenomena have been observed during OA, and both interleukin-1 and tumour necrosis factor-alpha seem to play key roles, as in RA. Although there is a dramatic difference between the 2 diseases in the intensity of inflammation, the inflammatory process is responsible for the synthesis of metalloproteinases and free oxygen radicals, and, subsequently, for progressive cartilage destruction. Both OA and RA engender important costs for the healthcare system. Direct costs result from practitioner visits, drug purchase and management, drug-related adverse effects, management or hospital care; indirect costs are linked to progressive functional disability. Although RA leads to significant individual costs, OA is more problematical for the healthcare system, since its prevalence is far higher than that of RA. Thus, rheumatic diseases have become a major public health problem. Optimal therapeutic strategies need to be determined in order to define the most effective procedure for controlling disease symptoms such as pain, stopping or slowing down disease progression and, finally, keeping patients active. But it is of paramount importance that the gain in efficacy be associated with a gain in drug safety.

Lequerré T, Quartier P, Rosellini D, Alaoui F, De Bandt M, Mejjad O, Kone-Paut I, Michel M, Dernis E, Khellaf M, Limal N, Job-Deslandre C, Fautrel B, Le Loët X, Sibilia J, Anonymous00361, Anonymous00362. · Rheumatology Department, Rouen University Hospital & Inserm 905, 76031 Rouen, France. · Ann Rheum Dis. · Pubmed #17947302 No free full text.

Abstract: BACKGROUND: Anakinra treatment has been reported to be effective in some patients with systemic-onset juvenile idiopathic arthritis (SoJIA) or adult-onset Still disease (AoSD). OBJECTIVES: To assess the efficacy and the safety of anakinra treatment in SoJIA and AoSD. METHODS: SoJIA and AoSD patients were treated with anakinra (1-2 mg/kg/day in children, 100 mg/day in adults); we analysed its effect on fever, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, numbers of swollen and tender joints, the assessment of disease activity (by physician and parent/patient) and pain (by parent/patient), and American College of Rheumatology (ACR) pediatric core set criteria for JIA activity. RESULTS: A total of 35 patients were included, 20 with SoJIA and 15 with AoSD. Their mean age (range) at the onset of treatment was 12.4 (3-23) and 38.1 (22-62) years, respectively; disease duration was 7.0 (1-16) and 7.8 (2-27) years, respectively. Active arthritis was present in all cases but one. Of the 20 SoJIA patients, 5 achieved ACR 50% improvement in symptoms (ACR50) response criteria at 6 months. Steroid dose had been decreased by 15% to 78% in 10 cases. A total of 11 of the 15 AoSD patients achieved at least a 50% improvement for all disease markers (mean follow-up: 17.5 (11-27) months). Steroids had been stopped in two cases and the dose was decreased by 45% to 95% in 12 patients. Two patients stopped anakinra due to severe skin reaction, and two patients due to infection: one visceral leishmaniasis and one varicella. CONCLUSION: Anakinra was effective in most AoSD patients, but less than half SoJIA patients achieved a marked and sustained improvement.

Fautrel B, Borget C, Rozenberg S, Meyer O, Le Loët X, Masson C, Koeger AC, Kahn MF, Bourgeois P. · Department of Rheumatology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · J Rheumatol. · Pubmed #9972972 No free full text.

Abstract: OBJECTIVE: Adult Still's disease (ASD) is a rare chronic polyarthritis, usually treated with corticosteroid therapy. Because some patients become dependent on high dose prednisone or are refractory to that treatment, and because adverse events are frequent with corticosteroid, we evaluated the efficacy of low dose methotrexate (MTX) as a second-line drug. METHODS: We retrospectively studied 26 patients with ASD treated with low dose MTX because their disease was either resistant to or dependent on corticosteroids. RESULTS: The group included 13 women and 13 men, with a mean age of 32.6 years at onset of ASD. Mean disease duration at the beginning of MTX treatment was 59.9 mo (range 7 to 444). Evaluation took place at the maximum followup, which averaged 48.9 mo (range 8 to 136). The mean dose of MTX was 11.5+/-3.6 mg/week (range 7.5 to 17.5). Twenty-three patients responded to MTX; 18 had complete remission. No difference was seen between patients with or without extraarticular manifestations. Leukocyte and neutrophil counts and erythrocyte sedimentation rate were significantly reduced (p = 0.0001). Daily prednisone intake decreased by 69% (21.5 mg) (p = 0.0001). Eleven patients were able to stop taking corticosteroids. One patient with AA amyloidosis renal failure died of neutropenia: this was the only serious adverse event. CONCLUSION: MTX is an effective second-line treatment of ASD that does not respond to prednisone. It allows significant reduction of corticosteroid doses, which is beneficial to these patients, who have frequent and numerous corticosteroid related adverse events.

Pham T, Claudepierre P, Constantin A, Fautrel B, Gossec L, Gottenberg JE, Goupille P, Hachulla E, Masson C, Morel J, Saraux A, Schaeverbeke T, Wendling D, Mariette X, Sibilia J. · Service de Rhumatologie, CHU Conception, Marseille, France. · Joint Bone Spine. · Pubmed #19560051 No free full text.

Abstract: OBJECTIVES: To elaborate a how-to-use abatacept material intended to help physicians in the management of patients with inflammatory diseases treated with this drug in routine practice. METHODS: 1) Selection of the relevant domains by a rheumatologists' panel; 2) Search for published evidence in each domain; 3) Elaboration of the clinical tool guide with a 3-level gradation of evidence (evidence-based medicine EBM, official recommendations and expert's opinion). The experts were 11 academic rheumatologists with a large experience in prescribing abatacept and in managing rheumatoid arthritis. They were all members of the CRI (Club Rhumatismes et Inflammation), a section of the French Rheumatology Society dedicated to the inflammatory rheumatic diseases. Each fact sheet was reviewed by two other experts; 4) Regular updating based on medical literature and postmarketing surveillance data. RESULTS: Four domains were considered relevant: abatacept contraindications, management of side effects or associated diseases appearing during abatacept treatment, management of "practical situations" such as surgery or pregnancy, physician and patient information. After the literature analysis and discussion during an experts' meeting, a consensus was reached on: a pre-treatment checklist aimed at searching abatacept contraindications; a what-to-do document when facing side effects or associated diseases (autoimmune pathology, bacterial or viral infections, cardiovascular diseases, intolerance to abatacept, solid or haematological malignancy) or "practical situations" (surgery, pregnancy, vaccination, travel, drug-drug interactions); an example of standard information letter to be addressed to the attending physician (rheumatologist and general practitioner); an example of standard information letter to be addressed to the patient. CONCLUSION: Based on both an EBM approach and an expert's opinion approach, this abatacept clinical tool guide should provide assistance to all physicians attending patients treated with abatacept. For a better implementation in clinical practice, this tool guide will be available online at www.cri-net.com and regularly updated.

Fautrel B, Guillemin F, Meyer O, de Bandt M, Berthelot JM, Flipo RM, Lioté F, Maillefert JF, Wendling D, Saraux A, Combe B, Le Loët X, Anonymous00044, Anonymous00045, Anonymous00046. · Department of Rheumatology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Arthritis Rheum. · Pubmed #19333993 No free full text.

Abstract: OBJECTIVE: To survey rheumatologists' preferences for the choice of a second-line disease-modifying antirheumatic drug (DMARD) after inadequate response with methotrexate (MTX) therapy in rheumatoid arthritis (RA). METHODS: Thirty-six rheumatologists stated their preferences for RA treatment after inadequate response with MTX therapy (optimal dose at least 6 months). From the initial scenario, we derived 54 vignettes varying by rheumatoid factor or anti-cyclic citrullinated peptide antibody presence, swollen joint count, Disease Activity Score in 28 joints, and structural damage. Respondents stated their preference among 5 therapeutic options: MTX continuation, switch to another conventional DMARD, addition of another conventional DMARD, addition of anakinra, or addition of a tumor necrosis factor (TNF) blocker. Presentation by pairs yielded 10 combinations of strategies for each variant, totaling 540 vignettes; participants evaluated a random sample of 180 vignettes. Determinants of each top-ranked option were analyzed by logistic regression. The compilation of these data served to define a therapeutic algorithm. RESULTS: The responses of 33 rheumatologists were analyzable. Therapeutic preferences corresponded to the top-ranked options. For patients with mild or moderately active RA, either a switch or step-up strategy to another conventional DMARD was top ranked. TNF blockers were preferred for RA patients with high disease activity or progressive structural damage. On the basis of these preferences, we developed a simple decision tree for use in daily clinical practice. CONCLUSION: Our simple, easy-to-use decision tree developed from rheumatologists' preferences for therapy after failure of MTX therapy in RA treatment may guide rheumatologists in daily practice to choose a second-line DMARD.

Lukas C, Guillemin F, Landewé R, van der Heijde D, Logeart I, Fautrel B, Daures JP, Combe B, Anonymous00090. · Immuno-Rhumatologie, Hôpital Lapeyronie, Montpellier, France. · Clin Exp Rheumatol. · Pubmed #19327234 No free full text.

Abstract: BACKGROUND: To describe the rate and timing of DMARD start in patients with early inflammatory arthritis in France, and to determine the factors leading to this treatment start. METHODS: The ESPOIR cohort study collects data on patients presenting with early arthritis. Baseline characteristics were assessed, and Cox regression analysis was performed to estimate the likelihood of starting DMARD treatment over time, adjusting for patient-, disease- and physician characteristics. RESULTS: Of the 775 analysed patients, 598 (77.2%) received at least 1 DMARD during the follow-up period, after a median time of 4.0 months. In general, a higher tender joint count, involvement of the hands, involvement of more than 3 joint groups, presence of abnormal CRP-levels or CCP-antibodies significantly increased the likelihood of being treated (p<0.01 for all determinants), as well as a positive result on the bilateral foot-squeeze test (p<0.04). In addition, a significant hetero-geneity in therapeutic strategy across the 14 tested French regions was found: adjusted hazard ratios for DMARD start ranged from 1 to 2.15 (p<0.01), depending on the region where a patient was followed. For anti-CCP test and swollen joint count we demonstrated a statistically significant interaction with geographic region, implying that these tests are interpreted differently across regions. The same factors that increased the likelihood to start a DMARD were related to an earlier start. CONCLUSION: Rate and timing of treatment start with DMARDs in patients with early inflammatory arthritis in France is determined by well known clinical and biochemical variables. Apart from these variables, however, unknown and intangible factors that seem to cluster geographically are responsible for important variations in practice performance.

Benhamou M, Rincheval N, Roy C, Foltz V, Rozenberg S, Sibilia J, Schaeverbeke T, Bourgeois P, Ravaud P, Fautrel B. · Department of Rheumatology, University of Paris VI, Pitie Salpetriere Hospital, Paris, France. · J Rheumatol. · Pubmed #19286850 No free full text.

Abstract: OBJECTIVE: To compare rheumatologists' prescription for first disease modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA) in real-life settings with 2 clinical practice guidelines (CPG), the French Society of Rheumatology/STPR 2004 and EULAR/ESCISIT 2007, and thus assess the gap between practices and guidelines. Method. ESPOIR was a French multicenter cohort study of 813 patients with early arthritis between 2002 and 2005. "Definite" and "probable" RA were defined according to ACR criteria and the level of diagnostic certainty. The objectives were to assess conformity between the observed first-line DMARD prescribed for those patients and the DMARD recommended in the guidelines; and to conduct a mail survey of patients' usual rheumatologists to investigate the reasons for their nonconformity with guidelines. RESULTS: In total 627 patients with definite or probable RA were identified. Conformity rates were 58% for STPR guidelines and 54% for EULAR guidelines. At 6 months, 83 (34%) patients with early RA did not receive any DMARD. Main determinants associated with conformity to guidelines were disease activity and presence of severity-predictive factors. The main reason leading to a discrepancy between guidelines and daily practice appeared to be diagnostic uncertainty, i.e., the difficulty to reliably assess RA diagnosis as early as the first visits to the rheumatologist. CONCLUSION: There is a substantial gap between CPG and rheumatologists' daily practice concerning the first DMARD to prescribe in early RA. This is explained mainly by diagnostic uncertainty. More attention should be paid in future guidelines to the diagnostic difficulties of early RA.

Chauffier K, London J, Beaudouin C, Fautrel B. · Service de rhumatologie, GH Pitié-Salpêtrière, AP-HP, Université Paris 6 Pierre et Marie Curie, UFR de médecine, Site Pitié-Salpêtrière, F-75013 Paris, France. · Presse Med. · Pubmed #19278814 No free full text.

Abstract: The efficacy of anakinra on both RA-related symptoms and structural damage has been demonstrated in several randomized controlled trials. However, its interest seems limited with regards to other biologic agents. Anakinra seems promising in the treatment of childhood or adult onset Still disease, after the failure of both high dose steroids and methotrexate. The efficacy of anakinra is dramatic in several hereditary auto-inflammatory syndromes. Anakinra could be an interesting drug for the treatment of neutrophilic dermatosis or relapsing chondritis, refractory to conventional agents. Injection site reactions and infections are the 2 main anakinra-related side effects.

Debiais S, Maillot F, Luca L, Buret J, Fautrel B, Renard JP. · CHRU de Tours, Service de Médecine Interne, Tours, France. · J Clin Rheumatol. · Pubmed #19033875 No free full text.

This publication has no abstract.

Rosenberg C, Etchepare F, Fautrel B, Bourgeois P. · Rheumatology Unit, La Pitié Salpêtrière Hospital, 49 bld de l'Hôpital, 75013 Paris, France. · Joint Bone Spine. · Pubmed #18996039 No free full text.

Abstract: OBJECTIVE: To evaluate the inter- and intra-observer agreement of ultrasonographic metacarpophalangeal joint static images in patients with rheumatoid arthritis by two investigators with different ultrasonographic experience. METHODS: Ultrasonography was performed by the senior on 386 metacarpophalangeal joints respectively in B-mode and 408 in power Doppler of 17 patients with active rheumatoid arthritis. A first interpretation was done and images were stored at examination time. Static images were then read twice by two independent investigators of different experiment (4-year and 1-year experience in musculoskeletal ultrasonography respectively for the senior and the junior). RESULTS: For the intra-investigator reproducibility kappa or weighted kappa coefficient ranged from 0.74 to 0.99 for the junior and the senior for B and power Doppler mode. For inter-investigator reproducibility kappa or weighted kappa coefficient ranged from 0.61 and 0.98 for qualitative B and power Doppler modes and semi-quantitative power Doppler. The inter-investigator weighted kappa was 0.49 for semi-quantitative B-mode. The agreement between the dynamic exam and the static exam; results were very good for both readers in power Doppler Mode (0.89). In B-Mode, they didn't reach statistical significance. The reliability for measuring synovial thickness was excellent--rho=0.7609 (p=0.00001). CONCLUSION: An experienced rheumatologist and a junior achieved high inter- and intra-observer agreement rates for the identification of synovitis and power Doppler activity for static images of ultrasonography. Trainees could use that method as a first step in US learning.

Lévy L, Fautrel B, Barnetche T, Schaeverbeke T. · Department of Rheumatology, University Hospital Pellegrin, Bordeaux, France. · Clin Exp Rheumatol. · Pubmed #18799105 No free full text.

Abstract: BACKGROUND: There is substantial evidence of excess cardiovascular morbidity and mortality in rheumatoid arthritis (RA) patients, but the related studies showed important variations in the estimation of the risk. We conducted a meta-analysis to evaluate more accurately the incidence of cardiovascular events, and the excess of cardiovascular risk in a population of RA patients. METHODS: The authors searched for observational studies accounting for the number of myocardial infarction or stroke events, using Medline, and congress abstracts published until February 2006. The populations studied were adults and RA diagnosis was based on the American College of Rheumatology (ACR) criteria. We calculated the incidence of myocardial infarction and cerebrovascular fatal events in RA patients and estimated the cardiovascular risk increase for RA patients compared with the control group. RESULTS: 17 publications and abstracts were identified, 15 were selected for the meta-analysis (two publications were excluded because of the lack of person-years information). The incidence of fatal myocardial infarction was 13.3 for 1000 RA patients-year (IC95%=[13-13.6]). The incidence of fatal cerebrovascular accident was 4.5 for 1000 RA patients-year (IC95%=[4.3-4.7]). Risk of myocardial ischemia in RA patients was about 1.63 compared to the general population (OR=1.63, IC95%=[1.34-2]). No excess was found for the risk of stroke event in RA patients. CONCLUSION: RA patients were reported to present an excess risk of fatal myocardial infarction compared to the general population. The prevention of cardiovascular complications, including management of cardiovascular risk factors and control of systemic inflammation, should be taken into account by the rheumatologist.

Fautrel B, Flipo RM, Saraux A. · Service de Rhumatologie, Groupe Hospitalier Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75651 Paris Cedex 13, France. · Rheumatology (Oxford). · Pubmed #18794185 No free full text.

Abstract: OBJECTIVES: Several anti-TNF-alpha prescription guidelines in RA have been published, among which those issued by the British (BSR) and French (SFR) Societies for Rheumatology in 2005 are the most comprehensive. Objectives of the PRISME II survey were to assess and compare eligibility for anti-TNF-alpha therapy of RA patients consulting their usual rheumatologist according to (i) the SFR and BSR guidelines and (ii) the rheumatologist's opinion. METHODS: PRISME II was a postal, cross-sectional, observational survey proposed to all office-based rheumatologists practising in France in 2005. Rheumatologists were to include three consecutive consulting anti-TNF-alpha-naïve RA patients. Disease activity was assessed using the disease activity score 28 (DAS28). Structural damage progression was estimated based on the reading by the usual rheumatologist. The factors determining eligibility in the rheumatologists' opinion were identified by a logistic regression analysis. RESULTS: Four hundred and thirty-four rheumatologists included 1132 patients. Ongoing RA structural progression was reported for 41% of the patients. According to the SFR and BSR criteria, 64 patients (7.0%) and 10 patients (0.9%), respectively, were eligible for anti-TNF-alpha therapy, while 10% were deemed eligible according to the rheumatologists' opinion. Determinants of eligibility according to the rheumatologists were: high disease activity (DAS28 >5.1), ongoing structural progression and elevated daily corticosteroid intake. These three determinants feature in the SFR guideline. CONCLUSIONS: The proportion of RA patients eligible for anti-TNF-alpha therapy varies greatly according to the BSR or SFR guidelines. In France, there is a remarkable convergence between rheumatologists' opinion and SFR guideline regarding the main factors to consider for initiation of an anti-TNF-alpha therapy.

Combe B, Benessiano J, Berenbaum F, Cantagrel A, Daurès JP, Dougados M, Fardellone P, Fautrel B, Flipo RM, Goupille P, Guillemin F, Le Loet X, Logeart I, Mariette X, Meyer O, Ravaud P, Rincheval N, Saraux A, Schaeverbeke T, Sibilia J. · University Hospital, Montpellier, France. · Joint Bone Spine. · Pubmed #17905631 No free full text.

Abstract: OBJECTIVES: The French Society of Rheumatology initiated a large national multicenter, longitudinal and prospective cohort, the so-called "ESPOIR cohort study" in order to set up databases to allow various investigations on diagnosis, prognostic markers, epidemiology, pathogenesis and medico-economic factors in the field of early arthritis and rheumatoid arthritis. METHODS: Patients were recruited if they had undifferentiated arthritis or rheumatoid arthritis, of less than 6 months disease duration and if they were DMARD and steroids naïve. Patients have then to be followed every 6 months during the first 2 years then every year during at least 10 years. Clinical, biological, radiographic and medico-economic databases have been constituted to fit in the different objectives of the project and more than 20 scientific studies have already been accepted by the scientific committee. RESULTS: 813 patients were included (76.75% were female). The mean age was 48.07+/-12.55 years. The mean delay from the onset of symptoms to referral to the rheumatologist was 74.8+/-76.6 days. Baseline swollen and tender joint counts were 7.19+/-5.37 and 8.43+/-7.01; DAS28 score was 5.11+/-1.31. CRP was abnormal in 38.9% of the patients; 44.2%, 45.8% and 38.8% had respectively IgM rheumatoid factor (RF), IgA RF and anti-CCP antibodies. HLA DRB1*01 or 04 genes were found in 56.7% of them. Finally, 22% of these patients had erosions on hand or feet at baseline.

Fautrel B, Benhamou M. · Service de rhumatologie, groupe hospitalier de la Pitié-Salpêtrière, université Paris-VI-Pierre-et-Marie-Curie, 83, boulevard de l'Hôpital, 75651 Paris cedex 13, France. · Gynecol Obstet Fertil. · Pubmed #17707673 No free full text.

Abstract: The desire of reproduction is a true challenge for the physicians in charge of patients with chronic inflammatory disorders such as rheumatoid arthritis or other connective tissue diseases. It requires: 1) the strict evaluation of the potential risks of flare of the rheumatic disease because of the pregnancy; 2) the assessment of risks on pregnancy outcome and fetus development; 3) the management of the different anti-rheumatic agents in order to maintain optimal control of disease activity and avoid any teratogenic problem. Besides this, it clearly appears that inflammatory rheumatic diseases may have an impact on patients' fertility, which may be explained by different mechanisms, physical, psychological, hormonal or immunological. Moreover, some treatments may directly affect fertility, which may justify specific managements in order to preserve gonadic functions.

Fautrel B, Clarke AE, Guillemin F, Adam V, St-Pierre Y, Panaritis T, Fortin PR, Menard HA, Donaldson C, Penrod JR. · Department of Rheumatology, University of Paris VI-Pierre et Marie Curie, Hospital Pitié-Salpêtrière, Paris, France. · Med Decis Making. · Pubmed #17409364 No free full text.

Abstract: BACKGROUND: Individuals' valuation of changes in health states in monetary terms have been measured by examining changes in the direct and indirect costs of disease and by the willingness-to-pay (WTP) methodology. METHODS: In 2002, a 2-part study was conducted in Quebec. In one part of the study, 121 rheumatoid arthritis (RA) patients from the McGill University Health Centre were mailed the Stanford Cost Assessment Questionnaire, which enabled the elicitation of direct costs and indirect costs, according to the friction cost and the human capital methods. The other part was a phone survey conducted in a representative sample of the general population and in the same sample of patients, aiming to elicit the societal WTP for a complete cure of RA in the context of 2 different scenarios: a public coverage or private insurance. These estimates were then compared. RESULTS: Estimates of the cost of illness of RA ranged from 11,717 to 28,498 Canadian Dollars (CAD) depending on the method. These estimates are higher than those previously published in Canada from the 1990s, which is partly due to the recent and costly biological therapies and to a change in the measurement of productivity losses. These estimates are somewhat lower than the societal WTP elicited from the WTP survey, that is, 26,717 and 36,817 CAD per RA case, depending on the public or private health insurance context in which the cure would be available. CONCLUSION: Given that neither method is ideal, data from both methods would provide an important sensitivity analysis when monetary estimates of health state changes are required.

Meyer O, de Bandt M, Berthelot JM, Cantagrel A, Combe B, Fautrel B, Flipo RM, Lioté F, Maillefert JF, Saraux A, Wendling D, Guillemin F, Le Loët X, Anonymous00174. · Department of Rheumatology, AP-HP, Bichat Paris 7 University Hospital, CHU Bichat, 46 rue Henri Huchard, 75018 Paris, France. · Joint Bone Spine. · Pubmed #17194614 No free full text.

Abstract: BACKGROUND: The objective was to develop a clinical practice format for choosing a second-line disease-modifying anti-rheumatic drug (DMARD) after a 6-month course of a first-line DMARD in patients with early RA. METHODS: A panel of 34 experts selected treatment option from various scenarios using the Thurstone pairwise method. The experts had to choose between two proposed DMARDs without proposing other options. The scenarios were obtained using the three items: DAS28, rheumatoid factor status and radiographic structural damage. A sample of 240 among 480 scenarios for each expert was taken at random. Responses given by at least 20% of the experts were considered pertinent. RESULTS: Recommendations for choosing a second DMARD for early RA after failure of a 6-month course of a first-line DMARD were established according to 4 parameters: type of first-line DMARD, activity, RF status and radiographic joint damage. The results of this study suggest that in patients with early RA who fail a 6-month course of first-line DMARD therapy, the best options may be addition of corticosteroid when disease activity is moderate to high and switching to a biologic agent when further radiographic joint damage occurs, particularly in patients with positive tests for RF. CONCLUSION: Although our scenarios did not include step-up (add instead of substitute) strategies, except for corticosteroids, we feel that the format presented here can optimise the management of patients with early RA seen in clinical practice.