Rheumatoid Arthritis: Schaeverbeke T

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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Moiton MP, Richez C, Dumoulin C, Mehsen N, Dehais J, Schaeverbeke T. · No affiliation provided · Clin Microbiol Infect. · Pubmed #17121619 No free full text.

Abstract: There is increasing interest concerning the possible impact of anti-tumour necrosis factor (TNF)-alpha therapeutic agents on the emergence of infections. However, these agents do not seem to increase the incidence of adverse infectious events significantly. Published observations concern mostly infections of the urinary and upper respiratory tracts that develop in the setting of co-morbidities, such as anterior or concomitant immunosuppressive treatment. Infliximab appears to increase the risk of tuberculosis, but this effect has not been observed with other anti-TNF-alpha agents. To better characterise the adverse infectious effects associated with these agents, physicians should be encouraged to notify the microbiological data relating to all cases.

Schaeverbeke T, Vicaut E, Cohen A, Ravaud P. · Service de Rhumatologie, CHU Pellegrin, Bordeaux 33000. · Presse Med. · Pubmed #17078593 No free full text.

Abstract: The cardiovascular impact of the non-steroidal anti-inflammatory drugs and the higher cardiovascular mortality during treatment of inflammatory rheumatism impose a rigorous evaluation of the cardiovascular risk of rheumatic patients. Large epidemiological studies have identified risk factors for cardiovascular diseases such as the age, male gender, family history (infarct, stroke), tobacco consumption, systolic arterial pressure, renal insufficiency, hypercholesterolemia, diabetes mellitis, sedentariness, obesity and "electric" ventricular hypertrophy. Some equations make it possible to evaluate the absolute cardiovascular risk at the individual level, which corresponds to the onset risk of a stroke in the 10 years to come in a subject according to the number and importance of each of his risk factors. It has been demonstrated that the correction of one or more risk factors reduce the overall cardiovascular risk justifying the strategies for evaluating this risk to define therapeutic intervention thresholds. The impact of a long-term anti-inflammatory treatment or an inflammatory disease such as rheumatoid arthritis has not been the subject of specific epidemiological study allowing these elements to be included in an equation of the estimation of the cardiovascular risk. However, the introduction of on anti-inflammatory treatment, likely to increase the cardiovascular risk of a patient, certainly justifies an evaluation of the absolute cardiovascular risk.

Sordet C, Cantagrel A, Schaeverbeke T, Sibilia J. · Service de Rhumatologie, CHU de Strasbourg, France. · Joint Bone Spine. · Pubmed #16376804 No free full text.

Abstract: Primary immune deficiencies (PIDs) are characterized by functional and/or quantitative abnormalities of one or more immune system components. Several bone and joint abnormalities can occur in patients with PID, with arthritis being the most common. Joint manifestations, of which arthritis is the most common, occur chiefly in humoral PIDs (agammaglobulinemia, common variable immunodeficiency, hyper-IgM syndromes, and IgA deficiency) and occasionally in other PIDs (chronic granulomatous disease and Wiskott-Aldrich syndrome). Monoarthritis or oligoarthritis is the usual pattern, although polyarthritis may occur, occasionally with nodules suggesting rheumatoid arthritis. Arthritis in patients with PID is usually infectious in nature, the most common causative organism being Mycoplasma, followed by Staphylococcus, Streptococcus, and Haemophilus. These bacteria can induce not only synovial infections, but also aseptic arthritogenic inflammatory responses. Arthritis having no demonstrable relation to chronic infection has been reported also and ascribed to dysimmunity-driven mechanisms that exhibit a number of specific features. Bone lesions are far less common and usually due to infections complicating humoral PID. Distinctive bone manifestations occur in a number of rare PIDs (e.g., hyper-IgE syndrome and Di George syndrome) and in syndromes characterized by spondyloepiphyseal dysplasia. Familiarity with PID syndromes both enhances the diagnostic capabilities of physicians and provides insight into the pathophysiology of bone and joint abnormalities associated with immune dysfunction. In children and occasionally in adults, a combination of bone and/or joint manifestations and hypogammaglobulinemia may indicate PID. When there is no evidence of lymphoproliferative disease, infection, or iatrogenic complications, investigations for PID should be obtained. PID-related arthritis is a unique model for studying the pathogenesis of presumably postinfectious arthritis and of inflammatory joint diseases including rheumatoid arthritis.

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.

Chêne G, Lequen L, Schaeverbeke T. · INSERM unit 330, Victor Segalen Bordeaux 2 University, France. · Rev Rhum Engl Ed. · Pubmed #10063530 No free full text.

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Bébéar CM, Schaeverbeke T, Bébéar C. · Bacteriology Laboratory, Bordeaux 2 University, France. · Rev Rhum Engl Ed. · Pubmed #10063527 No free full text.

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Schaeverbeke T, Bébéar CM, Clerc M, Lequen L, Bébéar C, Dehais J. · Rheumatology Department, Bordeaux II University, France. · Rev Rhum Engl Ed. · Pubmed #10063520 No free full text.

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Gonnet-Gracia C, Barnetche T, Richez C, Blanco P, Dehais J, Schaeverbeke T. · Department of Rheumatology, University Hospital Pellegrin, Bordeaux Cedex, France. · Clin Exp Rheumatol. · Pubmed #18578960 No free full text.

Abstract: OBJECTIVE: To investigate autoantibody induction in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in a cohort of French patients treated with TNF-alpha blockers. METHODS: We tested the serum of patients for antinuclear antibodies (ANA), anti-DNA antibodies and C4 complement at baseline, and for each infusion for infliximab, and at month 3, 6 and 12 for etanercept. We looked for all signs suggesting a drug-induced lupus. We tried to correlate ANA and anti-DNA development with various clinical data, especially the response to treatment. RESULTS: 229 patients were included in the study. 159 were treated with infliximab (98 RA and 61 AS) and 125 with etanercept (116 RA and 9 AS). In the infliximab group, 43.6% of RA patients and 27.1% of AS had significant levels of ANA at baseline. This proportion increased during the follow up to 73% in RA patients and 52% in AS patients. The proportion of patients positive for anti-DNA antibodies increased from 0% to 9.5% in RA group, and from 0% to 2% in AS group. In the etanercept group, 58.5% of these patients had significant levels of ANA at baseline; this proportion raised to 63.3% in patients previously treated with infliximab, and fell to 20.6% in the patients who never received TNF-alpha blockers. No significant variation of ANA, anti-DNA and C4 levels was observed in the etanercept group. Only three patients developed clinical manifestations (chilblain lupus) possibly related to these auto-antibodies, two with infliximab and one with etanercept. CONCLUSION: The ANA induction was only observed under infliximab therapy. Thus, ANA induction seems not to be a therapeutic class effect. This difference between infliximab and etanercept treatment may be the consequence of differential capacity of a monoclonal antibody and a soluble receptor in inducing apoptotic cell death of the cells expressing TNF on their membrane.

Bannwart B, Bertin P, Péhourcq F, Schaeverbeke T, Gillet P, Lefrançois G, Trèves R, Dehais J, Netter P, Gaucher A. · Rheumatology Department of Groupe Hospitalier Pellegrin, Bordeaux, France. · Int J Clin Pharmacol Ther. · Pubmed #11204935 No free full text.

Abstract: AIMS: The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in rheumatic diseases depends on their concentrations within the joint. We determined piroxicam concentrations in plasma and synovial fluid (SF) after a single oral dose of 20 mg in the form of one tablet of piroxicam-beta-cyclodextrin. METHODS: 45 patients, aged 21 to 84 years, presenting with an effusion of the knee, related to degenerative or inflammatory joint disease, were included in this study after having given their written consent. One blood and one SF sample were drawn concomitantly in each patient from 0.5 to 48 h after NSAID administration. Piroxicam assays were performed by high performance liquid chromatography. Pharmacokinetic parameters were obtained from the mean plasma and synovial concentrations measured at various sampling times. RESULTS: The peak concentration was higher in plasma (2.51+/-0.25 microg/ml) than in SF (1.31+/-0.76 microg/ml), but the elimination half-life was much longer in SF (90.7 h) than in plasma (32.5 h). The SF/plasma area under the concentration-time curve ratio (evaluating the quantity of NSAID transferred from the blood to the joint) was equal to 0.39. CONCLUSIONS: Piroxicam contained in piroxicam-beta-cyclodextrin diffused well into the SF where its pharmacokinetic profile corresponded to that of a long half-life NSAID.

Richez C, Schaeverbeke T, Dumoulin C, Dehais J, Moreau JF, Blanco P. · Département de Rhumatologie, CHU Bordeaux,Place Amélie Raba-Léon, 33076 Bordeaux, France. · Arthritis Res Ther. · Pubmed #19563672 links to  free full text

Abstract: INTRODUCTION: The objective of our study was to identify the significance of the subtypes of dendritic cell (DC), specifically myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), in rheumatoid arthritis (RA) pathogenesis through their longitudinal follow-up in patients receiving infliximab. METHODS: Circulating mDC and pDC levels were evaluated by flow cytometry in RA patients (n = 61) and healthy volunteers (n = 30). In RA patients, these levels were measured before and during infliximab therapy. Their counts were correlated to RA disease activity markers and anti-nuclear antibody occurrence. IFNalpha production was measured by ELISA in serum of RA patients and, in vitro, in supernatant of peripheral blood mononuclear cells stimulated by influenza virus in the presence or absence of infliximab. Statistical evaluations were based on Mann-Whitney tests or Wilcoxon's signed-rank tests. RESULTS: RA patients with active disease were characterized by a baseline decrease in both circulating pDCs and mDCs. Disease activity markers inversely correlated only with mDC level. This level increased in RA patients responsive to infliximab therapy, to reach the level observed in controls. Conversely, anti-nuclear antibody appearance during infliximab therapy correlated inversely with pDC level and was associated with increased serum IFNalpha level and circulating plasma cells number. In vitro studies revealed that infliximab kept pDCs in an IFNalpha secreting state upon viral stimulation allowing differentiation of B cells into anti-nuclear antibody-secreting plasma cells. CONCLUSIONS: This study reveals two distinct roles for pDC and mDC in RA. Circulating mDCs mainly contribute to RA activity, whereas pDCs seem to be involved in appearance of anti-nuclear antibodies under infliximab therapy through the ability of this drug to keep pDCs in an IFNalpha secreting state.

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.

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.

Rambert J, Mamani-Matsuda M, Moynet D, Dubus P, Desplat V, Kauss T, Dehais J, Schaeverbeke T, Ezzedine K, Malvy D, Vincendeau P, Mossalayi MD. · Groupe Thérapeutiques d'inflammation et d'infection, Laboratoire d'Immunologie et de Parasitologie, UFR Sciences Pharmaceutiques, Université Bordeaux 2, Bordeaux, France. · PLoS One. · Pubmed #19279679 links to  free full text

Abstract: BACKGROUND: CD23 is a differentiation/activation antigen expressed by a variety of hematopoietic and epithelial cells. It can also be detected in soluble forms in biological fluids. Initially known as the low-affinity receptor for immunoglobulin E (Fc epsilonRII), CD23 displays various other physiologic ligands such as CD21, CD11b/c, CD47-vitronectin, and mannose-containing proteins. CD23 mediates numerous immune responses by enhancing IgE-specific antigen presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells. CD23-crosslinking promotes the secretion of pro-inflammatory mediators from human monocytes/macrophages, eosinophils and epithelial cells. Increased CD23 expression is found in patients during allergic reactions and rheumatoid arthritis while its physiopathologic role in these diseases remains to be clarified. METHODOLOGY/PRINCIPAL FINDINGS: We previously generated heptapeptidic countrestructures of human CD23. Based on in vitro studies on healthy and arthritic patients' cells, we showed that CD23-specific peptide addition to human macrophages greatly diminished the transcription of genes encoding inflammatory cytokines. This was also confirmed by significant reduction of mediator levels in cell supernatants. We also show that CD23 peptide decreased IgE-mediated activation of both human and rat CD23(+) macrophages. In vivo studies in rat model of arthritis showed that CD23-blocking peptide ameliorates clinical scores and prevent bone destruction in a dose dependent manner. Ex-vivo analysis of rat macrophages further confirmed the inhibitory effect of peptides on their activation. Taken together our results support the role of CD23 activation and subsequent inflammatory response in arthritis. CONCLUSION: CD23-blocking peptide (p30A) prevents the activation of monocytes/macrophages without cell toxicity. Thus, targeting CD23 by antagonistic peptide decreases inflammatory markers and may have clinical value in the treatment of human arthritis and allergic reactions involving CD23.

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.

Rooryck C, Barnetche T, Richez C, Laleye A, Arveiler B, Schaeverbeke T. · Laboratoire de Génétique Humaine, Université Victor Segalen Bordeaux, Bordeaux Cedex, France. · Clin Exp Rheumatol. · Pubmed #18565259 No free full text.

Abstract: OBJECTIVE: Anti-TNF-alpha therapies are widely used in rheumatoid arthritis (RA) patients. Despite their clearly proven efficacy, some discrepancies were observed in the treatment response with 40% of non-responder patients. The aim of this study is to determine whether two functional single-nucleotide polymorphisms, V212F in the FCGR3A, and M196R in the TNFRSF1B genes correlate with rheumatoid arthritis susceptibility and response to anti-TNF-alpha therapy. METHODS: The population study was composed of a French cohort of 78 RA patients and 70 healthy controls. Allele and genotype frequencies were compared between patients and controls, according to their response to infliximab therapy, using the American College of Rheumatology (ACR) response criteria. RESULTS: No association was found between these two SNPs and RA susceptibility. A significant correlation was found between 196R allele carriers and low response to infliximab therapy. CONCLUSION: This is the first report of a statistically significant association between the TNFRSF1B-M196R SNP and response to infliximab in a French cohort. Larger studies are needed to confirm the relevance of this association.

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.

Martin K, Bentaberry F, Dumoulin C, Miremont-Salamé G, Haramburu F, Dehais J, Schaeverbeke T. · Département de Pharmacologie, Université Victor Segalen, Bordeaux cedex, France. · Pharmacoepidemiol Drug Saf. · Pubmed #16845649 No free full text.

Abstract: PURPOSE: (i) To monitor the potential clinical neurotoxic symptoms in patients treated with leflunomide in daily practice and (ii) to describe the characteristics of patients presenting with this peripheral nervous system symptoms. METHOD: All patients treated with leflunomide between May 2000 and April 2003 and followed in the rheumatology department of the University Hospital participated in the study. Data concerning treatment patterns with leflunomide, demographic and disease characteristics were obtained from clinical charts. Neuropathy was diagnosed with nerve conduction study (NCS). Cases of neuropathy were described and then compared to other patients using univariate analyses. RESULTS: One hundred and thirteen patients were included in the study. M/F sex ratio was 0.45. Mean age at start of treatment was 55.6 years (range = 27-81). During the study period, eight incident cases of peripheral neuropathy and two cases of worsening of preexisting neuropathy were reported (incidence: 9.8%). Compared with other patients, neuropathy cases were older (69 vs. 54 years, p = 0.0006), more often diabetic (30% vs. 2.9%, p = 0.009) and more often treated with potentially neurotoxic drugs (20% vs. 1.9%, p = 0.039). At least one risk factor (potentially neurotoxic drug or diabetes) was found in 50% of patients with neuropathy versus 4% of patients without neuropathy (56% PPV, 96% NPV). CONCLUSION: Cases of toxic neuropathy have been observed during treatment of rheumatoid arthritis with leflunomide. Their occurrence seems to be associated with known risk factors. Careful monitoring of the patient's neurological status during leflunomide treatment is therefore mandatory.

Pham T, Gossec L, Constantin A, Pavy S, Bruckert E, Cantagrel A, Combe B, Flipo RM, Goupille P, Le Loët X, Mariette X, Puéchal X, Schaeverbeke T, Sibilia J, Tebib J, Wendling D, Dougados M. · Service de rhumatologie, CHU de la Conception, Marseille, France. · Joint Bone Spine. · Pubmed #16690341 No free full text.

Abstract: OBJECTIVE: To develop clinical practice guidelines for the evaluation and management of cardiovascular risk in patients with rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: Recommendations were developed using the evidence-based approach and expert opinion: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing the recommendations; Evidence providing answers to the five questions was sought in the literature; Based on this evidence, recommendations were developed by a panel of experts. RESULTS: The recommendations were as follows: 1) In patients with RA, attention should be given to the risk of cardiovascular disease, which is responsible for an excess burden of morbidity and mortality; 2) It must be recognized that RA may be an independent cardiovascular risk factor. Persistent inflammation is an additional risk factor; 3) The cardiovascular risk should be evaluated, and modifiable risk factors should be corrected; 4) In patients with RA requiring glucocorticoid therapy, the need for cardiovascular risk minimization is among the reasons that mandate the use of the minimal effective dose; 5) It should be recognized that methotrexate may protect against cardiovascular mortality in patients with RA; 6) It should be recognized that TNFalpha antagonists remain contraindicated in patients with RA and severe heart failure. TNFalpha antagonists do not seem to worsen moderate heart failure and may protect against cardiovascular mortality; 7) AFSSAPS recommendations about LDL-cholesterol objectives should be followed, with active RA being counted as a cardiovascular risk factor; 8) In patients with RA, statin therapy should be considered only when cholesterol levels are elevated despite appropriate dietary treatment; 9) RA per se does not indicate aspirin for primary prevention. When aspirin is used for secondary prevention, it should be recognized that concomitant treatment with nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the antiplatelet effects and increase the gastrointestinal side effects of aspirin therapy.

Gossec L, Pavy S, Pham T, Constantin A, Poiraudeau S, Combe B, Flipo RM, Goupille P, Le Loët X, Mariette X, Puéchal X, Wendling D, Schaeverbeke T, Sibilia J, Tebib J, Cantagrel A, Dougados M. · Service de rhumatologie B, CHU de Cochin, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France. · Joint Bone Spine. · Pubmed #16626995 No free full text.

Abstract: OBJECTIVE: To develop clinical practice guidelines for the use of nonpharmacological treatments in patients with early rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: A scientific committee used a Delphi prioritization procedure to select five questions. Evidence providing answers to the five questions was sought in the literature and presented to a panel of rheumatologists. The panel developed five detailed recommendations, filling gaps in evidence with their expert opinion. The strength of each recommendation was determined. RESULTS: Of the 565 publications retrieved by the literature review, 198 were included in the analysis. The five recommendations on nonpharmacological treatments for early RA were validated by a final vote among all participants. The recommendations are as follows: (1) physicians may decide to provide joint protection education to patients with potentially severe early RA, with the knowledge that structured joint protection programs have not been found effective; (2) physical exercise and sports can be recommended to patients with early RA; muscle strength exercises are advisable; (3) in patients with early RA, metatarsal pain and/or foot alignment abnormalities should be looked for regularly, and appropriate insoles should be prescribed if needed; (4) dietary measures and nutritional supplements are not indicated as part of the treatment of early RA; (5) elimination diets, particularly those with low intakes of dairy products, should be discouraged in patients with early RA. CONCLUSION: These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.

Pavy S, Constantin A, Pham T, Gossec L, Maillefert JF, Cantagrel A, Combe B, Flipo RM, Goupille P, Le Loët X, Mariette X, Puéchal X, Schaeverbeke T, Sibilia J, Tebib J, Wendling D, Dougados M. · Service de rhumatologie A, CHU Cochin, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France. · Joint Bone Spine. · Pubmed #16626993 No free full text.

Abstract: OBJECTIVES: To develop clinical practice guidelines for the use of methotrexate in rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing recommendations. Evidence providing answers to the five questions was sought in the Cochrane databases, PubMed, and proceedings of meetings of the French Society for Rheumatology, European League Against Rheumatism, and American College of Rheumatology. Using this evidence, a group of rheumatologists developed and validated the recommendations. For each recommendation, the level of evidence and the extent of agreement among experts were specified. RESULTS: The recommendations were as follows: 1: The starting dosage for methotrexate in patients with RA should not be less than 10 mg/week and should be determined based on disease severity and patient-related factors; 2: When a patient with RA shows an inadequate response to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20 mg/week, according to tolerance and patient-related factors; 3: When starting methotrexate treatment in a patient with RA, preference should be given to the oral route. A switch to the intramuscular or subcutaneous route should be considered in patients with poor compliance, inadequate effectiveness, or gastrointestinal side effects; 4: At present, there is no evidence indicating that a change in methotrexate dosage is in order when a TNF antagonist is given concomitantly; 5: The investigations that are mandatory before starting methotrexate therapy in a patient with RA consist of a full blood cell count, serum transaminase levels, serum creatinine with computation of creatinine clearance, and a chest radiograph. In addition, serological tests for the hepatitis viruses B and C and a serum albumin assay are recommended. In patients with a history of respiratory disease or current respiratory symptoms, lung function tests with determination of the diffusing capacity for carbon monoxide are recommended; 6: Investigations that are mandatory for monitoring methotrexate therapy in patients with RA consist of full blood cell counts and serum transaminase and creatinine assays. These tests should be obtained at least once a month for the first 3 months then every 4-12 weeks; 7: Folate supplementation can be given routinely to patients treated with methotrexate for RA. In practice, a minimal dosage of 5 mg of folic acid once a week, at a distance from the methotrexate dose, is appropriate; 8: In the event of respiratory symptoms possibly related to methotrexate toxicity, the drug must be stopped and symptom severity evaluated. Should evidence of serious disease be found, the patient should be admitted immediately or advice from a pulmonologist should be obtained immediately. CONCLUSION: Recommendations about methotrexate therapy for RA were developed. These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.

Richez C, Blanco P, Lagueny A, Schaeverbeke T, Dehais J. · Service de Rhumatologie, Groupe Hospitalier Pellegrin, CHU de Bordeaux, Bordeaux, France. · Neurology. · Pubmed #15851749 No free full text.

Abstract: Tumor necrosis factor-alpha (TauNuFalpha) blockers are effective in the treatment of inflammatory arthritis but can induce autoimmune disorders including multiple sclerosis. Described are two patients who developed chronic inflammatory demyelinating polyneuropathy after initiation of anti-TNFalpha treatment.

Gossec L, Fautrel B, Pham T, Combe B, Flipo RM, Goupille P, Le Loet X, Mariette X, Puéchal X, Wendling D, Schaeverbeke T, Sibilia J, Sany J, Dougados M. · Rheumatology Department, Cochin Teaching Hospital, Paris, France. · Joint Bone Spine. · Pubmed #15850994 No free full text.

Abstract: 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.

Pham T, Gossec L, Fautrel B, 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, CHU de la Conception, Marseille, France. · Joint Bone Spine. · Pubmed #15850993 No free full text.

Abstract: 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.

Martin K, Bentaberry F, Dumoulin C, Dehais J, Haramburu F, Bégaud B, Schaeverbeke T. · Department de Pharmacologie, INSERM U657, IFR 99, France. · Clin Exp Rheumatol. · Pubmed #15789891 No free full text.

Abstract: OBJECTIVE: Leflunomide, an immunosuppressant agent for treating rheumatoid arthritis, was first marketed in France in 2000. Three years after its launch, we sought to assess its prescription patterns in the real world of prescription and use, and to see if its efficacy and safety profiles observed during clinical trials were confirmed. METHODS: All patients treated with leflunomide from May 2000 to April 2003 in the Department of Rheumatology of the Bordeaux University Hospital were identified, and their treatment patterns and outcome ascertained. This was compared to data from clinical trials. RESULTS: 116 were included (mean age = 55 years, 70% women). Almost 21.7% stopped treatment for lack of efficacy (after a mean delay of 3.6 months), 16% for secondary loss of efficacy (median = 7 months), and 32% for the occurrence of an adverse event (half within 4 months). Over a similar time frame in clinical trials, in patients of about the same age and sex but with less severe disease, the corresponding figures were 7-17% for lack or loss of efficacy, and 14-22% for adverse effects. At one year of follow-up, the discontinuation rate was 70% in the cohort compared to 28-47% in clinical trials. DISCUSSION: The differences between the two populations confirm the need to conduct post-marketing studies in order to obtain better knowledge on the effectiveness and safety of a new drug. In many cases, a simple drug utilization study can provide relevant information on the degree of shift between populations included in clinical trials and those treated in real life.