Rheumatoid Arthritis: De Bandt M

Weber AJ, De Bandt M. · Service de rhumatologie, centre hospitalo-universitaire and INSERM U479, Faculté Xavier Bichat, Paris, France. · Joint Bone Spine. · Pubmed #11143903 No free full text.

Abstract: In rheumatoid arthritis, the vascular endothelium is among the key targets for circulating mediators of inflammation and controls the trafficking of cells and molecules from the bloodstream toward the synovial tissue. Local blood vessel proliferation allows the pannus to develop and grow, thereby promoting cartilage and bone destruction and joint remodeling. Angiogenesis, the production of new capillaries from preexisting blood vessels, is a key process in rheumatoid arthritis that involves multiple substances such as cytokines, chemokines, growth factors, cell adhesion molecules, proteinases, proteinase inhibitors, and matrix proteins. In animal models of arthritis, angiogenesis inhibitors have been found to improve clinical and radiological outcomes, opening up the possibility of therapeutic applications in humans. Before this possibility is realized, the steady accumulation of data on the mechanisms that regulate angiogenesis will have to continue until a clear picture of angiogenesis is formed.

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.

Berthelot JM, De Bandt M, Goupille P, Solau-Gervais E, Lioté F, Goeb V, Azaïs I, Martin A, Pallot-Prades B, Maugars Y, Mariette X, Anonymous00064. · Service de Rhumatologie, Hôtel-Dieu, CHU Nantes, 44093, Nantes Cedex 01, France. · Joint Bone Spine. · Pubmed #19059799 No free full text.

Abstract: OBJECTIVE: To report on the outcome of 15 cases of pregnancies in women treated with anti-TNF drugs during conception or pregnancy METHODS: French rheumatologists connecting to the web-site of CRI site: http://www.cri-net.com were asked to fill in a structured questionnaire reporting the outcome of pregnancy in women still treated by a TNF blocker at the time of conception. RESULTS: Spondylarthropathies (n=8), rheumatoid arthritis (n=4), juvenile idiopathic arthritis (n=2), and psoriatic arthritis (n=1) were treated by infliximab (n=3), adalimumab (n=2), or etanercept (n=10). Miscarriages occurred twice, and elective termination was preferred once. Anti-TNF had been administered during the first, second and third trimester of pregnancy in 12, three and two cases. The 12 babies were in good condition, without apparent malformation or symptoms of neonatal illnesses. CONCLUSION: The number of reported cases exceeds 300, but only 29 women were treated during their whole pregnancy. The rate of congenital malformations observed so far might appear reassuring compared to the general population for women exposed only during conception. Conversely, there are too few reports of exposure during pregnancy to allow any conclusion about the safety of TNF blockers, and additional long term follow-up of children would be welcome in order to rule out minor forms of VACTERL association that might have been overlooked at birth.

Saint Marcoux B, De Bandt M, Anonymous00468. · Service de Rhumatologie, Robert Ballanger Hospital, 93600, Aulnay sous Bois, France. · Joint Bone Spine. · Pubmed #17127088 No free full text.

Abstract: TNFalpha antagonists are effective in the treatment of chronic inflammatory joint disease. Despite a good overall safety profile, they can induce a number of adverse effects, including autoimmunity and infections. A link between TNFalpha antagonists and vasculitides has been suggested. METHODS: Between December 2004 and January 2005, a nationwide survey was conducted among 1200 hospital-based rheumatologists and internists in France, who were asked to report cases of vasculitis in patients taking TNFalpha antagonists. RESULTS: The survey identified 39 cases (32 women) of vasculitis during TNFalpha antagonist therapy. The joint disease was rheumatoid arthritis (RA) in 34 patients (including four without rheumatoid factor), juvenile idiopathic arthritis in two patients, ankylosing spondylitis in two patients, and psoriatic arthritis in one patient. Mean disease duration was 14.1+/-8.7 years. The TNFalpha antagonist was etanercept in 21 patients, infliximab in 15, adalimumab in 2, and another drug in 1; mean treatment duration was 9.6 months. The manifestations of vasculitis involved the skin (n=32); peripheral nervous system (n=9); kidney (n=7); central nervous system (n=3); pleura (n=2), pericardium (n=2); and the lung, gallbladder, and heart (n=1 each). Antinuclear factor (ANF) was present in 22 patients, hypocomplementemia in 6, and antineutrophil cytoplasmic antibody in 5. Histology (30 biopsies from 27 patients) showed nonnecrotizing vasculitis in 12 patients, necrotizing vasculitis in 7, an inflammatory dermal infiltrate without vasculitis in 3, extravascular necrotic granulomas in 2, chilblain lupus in 1, and cicatricial fibro-inflammatory changes in 1. Renal biopsy in three patients showed extracapillary glomerulonephritis with IgA deposits (n=2) or active floccular necrosis against a background of glomerular sclerosis (n=1). TNFalpha antagonist therapy was stopped in 33 patients, among whom 18 recovered without further treatment and 14 required high-dose glucocorticoids and/or immunosuppressant therapy, which ensured symptom resolution within a few weeks. The remaining patient died with multiple organ failures. DISCUSSION: The relative contributions of TNFalpha antagonist therapy and of the underlying disease to the development of vasculitis cannot be determined. Features that suggest a causal link between TNFalpha antagonists and vasculitis include the short time from TNFalpha antagonist initiation to vasculitis onset; the favorable response to discontinuation of TNFalpha antagonist therapy; and the development of systemic vasculitis in patients with rheumatoid factor-negative RA, in adults with juvenile-onset arthritis, and in patients with spondyloarthropathies.

Le Loët X, Berthelot JM, Cantagrel A, Combe B, De Bandt M, Fautrel B, Flipo RM, Lioté F, Maillefert JF, Meyer O, Saraux A, Wendling D, Guillemin F. · Department of Rheumatology, Rouen University Hospital, France. · Ann Rheum Dis. · Pubmed #15994280 links to  free full text

Abstract: OBJECTIVE: To elaborate a clinical practice decision tree for the choice of the first disease modifying antirheumatic drug (DMARD) for untreated rheumatoid arthritis of less than six months' duration. METHODS: Four steps were employed: (1) review of published reports on DMARD efficacy against rheumatoid arthritis; (2) inventory of the information available to guide DMARD choice; (3) selection of the most pertinent information by 12 experts using a Delphi method; and (4) choice of DMARDs in 12 clinical situations defined by items selected in step 3 (28 joint disease activity score (DAS 28): < or =3.2; >3.2 and < or =5.1; >5.1; rheumatoid factor status (positive/negative); structural damage (with/without)-that is, 3 x 2 x 2). Thus, multiplied by all the possible treatment pairs, 180 scenarios were obtained and presented to 36 experts, who ranked treatment choices according to the Thurstone pairwise method. RESULTS: Among the 77 items identified, 41 were selected as pertinent to guide the DMARD choice. They were reorganised into five domains: rheumatoid arthritis activity, factors predictive of structural damage; patient characteristics; DMARD characteristics; physician characteristics. In the majority of situations, the two top ranking DMARD choices were methotrexate and leflunomide. Etanercept was an alternative for these agents when high disease activity was associated with poor structural prognosis and rheumatoid factor positivity. CONCLUSIONS: Starting with simple scenarios and using the pairwise method, a clinical decision tree could be devised for the choice of the first DMARD to treat very early rheumatoid arthritis.

De Bandt M, Sibilia J, Le Loët X, Prouzeau S, Fautrel B, Marcelli C, Boucquillard E, Siame JL, Mariette X, Anonymous00326. · Rheumatology Department, Hôpital Robert Ballanger, Aulnay sous Bois, France. · Arthritis Res Ther. · Pubmed #15899041 links to  free full text

Abstract: The development of drug-induced lupus remains a matter of concern in patients treated with anti-tumour necrosis factor (TNF) alpha. The incidence of such adverse effects is unknown. We undertook a retrospective national study to analyse such patients.Between June and October 2003, 866 rheumatology and internal medicine practitioners from all French hospital centres prescribing anti-TNF in rheumatic diseases registered on the website of the 'Club Rhumatismes et Inflammation' were contacted by email to obtain the files of patients with TNF-induced systemic lupus erythematosus. Twenty-two cases were collected, revealing two aspects of these manifestations. Ten patients (six patients receiving infliximab, four patients receiving etanercept) only had anti-DNA antibodies and skin manifestations one could classify as 'limited skin lupus' or 'toxidermia' in a context of autoimmunity, whereas 12 patients (nine patients receiving infliximab, three patients receiving etanercept) had more complete drug-induced lupus with systemic manifestations and at least four American Congress of Rheumatology criteria. One patient had central nervous system manifestations. No patients had lupus nephritis. The signs of lupus occurred within a mean of 9 months (range 3-16 months) in patients treated with infliximab and within a mean of 4 months (range 2-5 months) in patients treated with etanercept. In all cases after diagnosis was determined, anti-TNF was stopped and specific treatment introduced in eight patients: two patients received intravenous methylprednisolone, four patients received oral steroids (15-35 mg/day), and two patients received topical steroids. Lupus manifestations abated within a few weeks (median 8 weeks, standard deviation 3-16) in all patients except one with longer-lasting evolution (6 months). At that time, cautious estimations (unpublished data from Schering Plough Inc. and Wyeth Inc.) indicated that about 7700 patients had been exposed to infliximab and 3000 to etanercept for inflammatory arthritides in France. It thus appears that no drug was more implicated than the other in lupus syndromes, whose incidence was 15/7700 = 0.19% with infliximab and 7/3800 = 0.18% with etanercept.Clinicians should be aware that lupus syndromes with systemic manifestations may occur in patients under anti-TNF alpha treatment.

Gorwood P, Pouchot J, Vinceneux P, Puéchal X, Flipo RM, De Bandt M, Adès J, Anonymous00118. · Hôpital Louis Mourier (AP-HP), Service de Psychiatrie, 178 rue des Renouillers, 92700 Colombes, France. · Schizophr Res. · Pubmed #14693349 No free full text.

Abstract: There is wide evidence for a decreased risk of rheumatoid arthritis in patients with schizophrenia. Nevertheless, very few studies have looked at the risk of schizophrenia in a group of patients with rheumatoid arthritis. We prospectively investigated, with the SCL-90R, 220 consecutive outpatients with rheumatoid arthritis and 196 consecutive outpatients with various medical conditions, half of them suffering from psoriatic arthritis (a medical condition close to rheumatoid arthritis). The SCL-90R appears to be a valuable tool to distinguish patients with schizophrenia from the outpatients of our sample, the former having more "paranoid ideation" (p = 0.004) and more "psychoticism" (p < 0.001) than the latter. The "paranoid ideation" dimension was significantly lower (25% decrease) in the sample of patients with rheumatoid arthritis compared to the combined control group (p = 0.005), ratings under the median value being more frequent in the former group (p = 0.025). Confounding factors might not explain this difference according to the regression logistic analysis performed. As patients with rheumatoid arthritis have a lower score of paranoid ideation than controls in our sample, even after controlling for age, gender and severity of the disease, these data represent further evidence for a decreased risk of schizophrenia in individuals with rheumatoid arthritis.

De Bandt M, Ben Mahdi MH, Ollivier V, Grossin M, Dupuis M, Gaudry M, Bohlen P, Lipson KE, Rice A, Wu Y, Gougerot-Pocidalo MA, Pasquier C. · Institut Nationale de la Santé et de la Recherche Médicale, Unité 479, Faculté Xavier Bichat, Paris, France. · J Immunol. · Pubmed #14568965 links to  free full text

Abstract: It was recently shown that vascular endothelial growth factor (VEGF), a growth factor for endothelial cells, plays a pivotal role in rheumatoid arthritis. VEGF binds to specific receptors, known as VEGF-RI and VEGF-RII. We assessed the physical and histological effects of selective blockade of VEGF and its receptors in transgenic K/BxN mice, a model of rheumatoid arthritis very close to the human disease. Mice were treated with anti-mouse VEGF Ab, anti-mouse VEGF-RI and -RII Abs, and an inhibitor of VEGF-RI tyrosine kinase. Disease activity was monitored using clinical indexes and by histological examination. We found that synovial cells from arthritic joints express VEGF, VEGF-RI, and VEGF-RII. Treatment with anti-VEGF-RI strongly attenuated the disease throughout the study period, while anti-VEGF only transiently delayed disease onset. Treatment with anti-VEGF-RII had no effect. Anti-VEGF-RI reduced the intensity of clinical manifestations and, based on qualitative and semiquantitative histological analyses, prevented joint damage. Treatment with a VEGF-RI tyrosine kinase inhibitor almost abolished the disease. These results show that VEGF is a key factor in pannus development, acting through the VEGF-RI pathway. The observation that in vivo administration of specific inhibitors targeting the VEGF-RI pathway suppressed arthritis and prevented bone destruction opens up new possibilities for the treatment of rheumatoid arthritis.

Berthelot JM, Bernelot-Moens HJ, Klarlund M, McGonagle D, Calin A, Schumacher HR, Combe B, De Bandt M, Drosos AA, Flipo RM, Harris BJ, Kaarela K, Le Goff P, Meyer O, Punzi L, Zerbini CA, Saraux A, Anonymous00207. · Department of Rheumatology, Nantes University Medical School, CHU Nantes, France. · Clin Exp Rheumatol. · Pubmed #12051392 No free full text.

Abstract: OBJECTIVES: To determine areas of agreement and disagreement among experts in the interpretation of the published criteria for RA (ACR) and spondylarthropathies ( ESSG). METHODS: Thirty-two experts (16 from France and 16 from 10 other countries) replied anonymously to a mailed questionnaire. RESULTS: Tenosynovitis and 'sausage-like' painless swelling of the toes were considered as criteria for RA by 18 and 14 experts, respectively. The definition of symmetry differed widely among experts (symmetry of only one group of joints was sufficient for 13). Twenty-five experts considered erosions of other joints than the wrists and fingers as a criterion for RA, 17 thought that fulfilment of criteria could be achieved cumulatively, and 19 would appreciate clarifications of the current criteria. Among possible clarifications for RA, it was frequently recommended that morning stiffness and nodules be eliminated and that new marker antibodies, X-rays of the feet, and exclusion criteria be added. Twenty-three of the 29 experts who gave an opinion (79%) agreed with the notion of SP in the absence of axial signs and sacroiliitis, 26/31 (84%) indicated that a patient can have both RA and SP, and 19/30 (63%) thought that RA and SP could be regarded as syndromes more than diseases. Only 5/32 experts relied more on the criteria than on their clinical judgement in diagnosing RA. CONCLUSIONS: There would seem to be a needfor the optimisation of RA and ESSG criteria, particularly within the context of early arthritis.

De Bandt M, Grossin M, Driss F, Pincemail J, Babin-Chevaye C, Pasquier C. · INSERM U479, Faculté Xavier Bichat, and Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri Huchard, Paris 75018, France. · Arthritis Rheum. · Pubmed #11840456 No free full text.

Abstract: OBJECTIVE: Reactive oxygen species are thought to play a role in rheumatoid arthritis (RA) in humans. We postulated that antioxidant treatment could have a beneficial effect in this disease. We therefore investigated the effects of vitamin E in the transgenic KRN/NOD mouse model of RA. METHODS: Mice were treated by gavage with oral vitamin E (alpha-tocopherol). Clinical, histologic, and biochemical parameters were assessed for 6 weeks. RESULTS: Vitamin E treatment did not modify the clinical features of the disease (date of onset or disease intensity, as measured by the articular index), but it did prevent joint destruction, as measured by qualitative and semiquantitative analyses. Redox status did not differ between treated and control mice. White blood cell chemiluminescence was higher in transgenic KRN/NOD mice than in controls, but vitamin E treatment attenuated this difference. Vitamin E treatment of the transgenic animals led to a significant decrease in the levels of interleukin-(IL-1beta) but not tumor necrosis factor alpha. CONCLUSION: Vitamin E seems to uncouple joint inflammation and joint destruction in this model of RA, with a beneficial effect on joint destruction. Since many investigations are currently in progress to evaluate the benefit of interventions targeted toward anti-IL-1beta, our findings suggest opportunities of therapeutic interest in human RA.

Hayem G, De Bandt M, Palazzo E, Roux S, Combe B, Eliaou JF, Sany J, Kahn MF, Meyer O. · Rheumatology Department, Bichat Teaching Hospital, Paris, France. · Ann Rheum Dis. · Pubmed #10225814 links to  free full text

Abstract: OBJECTIVES: Stress proteins (HSPs) are highly conserved immunodominant antigens found in various species. The purpose of this study was to assess the prevalence and prognostic significance of antibodies to HSC 70 kDa and HSP 90 kDa in three groups of patients with longstanding rheumatoid arthritis (RA) defined based on the severity of articular erosions. METHODS: 73 patients with longstanding (> 6 years) RA whose HLA-DR genotype was known were divided in three groups according to Larsen's score and compared with 47 recent onset (<1 year) RA patients and with control groups composed of patients with other inflammatory diseases (n=137) or of normal controls (n=48). IgGs and IgMs to HSC 70 kDa and HSP 90 kDa were determined using an ELISA with purified bovine HSC 70kDa or HSP 90 kDa. RESULTS: Concentrations of IgGs and IgMs to HSC 70 were significantly increased in 41.1% and 42.5% of longstanding RA patients, respectively. Corresponding figures for IgGs and IgMs to HSP 90 were 39.7% and 56%. IgMs to HSC 70 and HSP 90 were less frequent in recent onset RA (19% and 13% respectively). Among the groups with other inflammatory diseases, only the MCTD group exhibited high frequencies of IgGs to HSC 70 (80%) and HSP 90 (85%). DRB1*0401 positive RA patients (n=23) were not more likely to have increased concentrations of antibodies to HSC 70 kDa or HSP 90 kDa than other RA patients (DR4 positive but DRB1*0401 negative, or DR1 positive, n=31; or negative for both DR4 and DR1, n=14). IgGs to HSP 90 kDa were significantly more frequent (p<0.05) in longstanding RA patients whose Larsen's score was 4 or more (57%) than in those whose Larsen's score was 2 or 3 (39.4%) or less than 2 (16%). No associations were found between Larsen's score and IgGs or IgMs to HSC 70 kDa or IgMs to HSP 90 kDa. A significant correlation was demonstrated between IgGs to HSP 90 kDa and two other serological markers for RA, rheumatoid factor, and anti-Sa antibody; there were no correlations with antikeratin antibody, antiperinuclear factor, or anti-RA 33. CONCLUSION: IgGs to HSP 90 kDa are most common in longstanding RA patients with articular erosions, suggesting that they may be related to the articular prognosis in RA

De Bandt M, Saint-Marcoux B. · No affiliation provided · Ann Rheum Dis. · Pubmed #19088261 No free full text.

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Aouba A, De Bandt M, Aslangul E, Atkhen N, Patri B. · No affiliation provided · Rheumatology (Oxford). · Pubmed #12771439 links to  free full text

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Weber AJ, De Bandt M, Gaudry M. · No affiliation provided · J Rheumatol. · Pubmed #10990256 No free full text.

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