Rheumatoid Arthritis: Bourgeois P

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, 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.

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.

Tebib J, Mariette X, Bourgeois P, Flipo RM, Gaudin P, Le Loët X, Gineste P, Guy L, Mansfield CD, Moussy A, Dubreuil P, Hermine O, Sibilia J. · Service de Rhumatologie, Centre Hospitalier Lyon-Sud, 765 chemin du Grand-Revoyet, 69495 Pierre-Bénite, France. · Arthritis Res Ther. · Pubmed #19549290 links to  free full text

Abstract: INTRODUCTION: Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a potent and selective protein tyrosine kinase inhibitor of c-KIT, in the monotherapy treatment of DMARD-refractory RA. METHODS: This was a multicentre, uncontrolled, open-label, randomised, dose-ranging, phase 2a trial. Masitinib was administered orally to 43 patients who had inadequate response to DMARDs, at initial randomised dosing levels of 3 and 6 mg/kg per day over a 12-week period. Dose adjustment was permitted based upon tolerability and response criteria. Efficacy was assessed via American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) responses, disease activity score using 28 joint counts (DAS28), index of improvement in RA (ACRn) and C-reactive protein (CRP) improvement, relative to baseline at week 12. RESULTS: Improvement was observed in all efficacy endpoints, including ACR20/50/70 scores of 54%, 26% and 8%, respectively, and a reduction in CRP level by greater than 50% for approximately half the population. This improvement was sustainable throughout an extension phase (> 84 weeks) and was also independent of initial DMARD resistance (anti-tumour necrosis factor-alpha and/or methotrexate). A relatively high patient withdrawal rate (37%) required the use of last observation carried forward (LOCF) data imputation. Incidence of adverse events was high (95%), although the majority were of mild or moderate severity with a considerable decline in frequency observed after 12 weeks of treatment. Two nonfatal serious adverse events were reported. Dose-response analyses tentatively indicate that an initial dosing level of 6.0 mg/kg per day administered orally in two daily intakes is the most appropriate, based upon potency and tolerability trends. CONCLUSIONS : Treatment with masitinib improved DMARD-refractory active RA. Following an initial high incidence of mostly mild to moderate side effects during the first 12 weeks of treatment, masitinib appears to be generally well tolerated. This, together with evidence of a sustainable efficacy response, suggests that masitinib is suitable for long-term treatment regimens. Since this was the first study of masitinib in a nononcologic pathology, the relatively high patient withdrawal rate observed can be partly attributed to a highly cautious response to adverse events. There is sufficient compelling evidence to warrant further placebo-controlled investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00831922.

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.

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.

Karie S, Gandjbakhch F, Janus N, Launay-Vacher V, Rozenberg S, Mai Ba CU, Bourgeois P, Deray G. · Department of Nephrology, Hôpital Pitié-Salpêtrière, 47-83, boulevard de l'hôpital, 75013 Paris, France. · Rheumatology (Oxford). · Pubmed #18238787 No free full text.

Abstract: OBJECTIVES: The prevalence of kidney disease (KD) indicators together with the profile of RA drugs prescribed in RA patients was investigated in the MATRIX study (MeThotreXate And Renal Insufficiency). METHODS: Renal function (RF) was assessed using Cockcroft-Gault (CG) and abbreviated Modification of Diet in Renal Disease (aMDRD) study formulae. RESULTS: Serum creatinine (SCr) was normal in 81.4% of the 129 patients included. According to the National Kidney Foundation (NKF) classification, the distribution by stage of KD was, using the aMDRD and CG formulae, as follows: stage 1: 11.3% and 11.4%; stage 2: 20.0% and 20.3%; stage 3: 15.0% and 24.1%; stage 4: 0% and 1.3%; stage 5: 0%. Proteinuria, haematuria and leucocyturia were observed in 16%, 17% and 20% of the patients, respectively. Using the aMDRD and CG formulae, 36% and 38% of the prescriptions made in patients with glomerular filtration rate (GFR) <60 ml/min required a dosage adjustment. Among the patients with GFR <60 ml/min, 83-90% received at least one drug that required a dosage adjustment and 67-70% received at least one drug that was potentially nephrotoxic, according to aMDRD or CG formulae, respectively. Five (50%) and 8 (47%) patients did not have appropriate MTX dosage adjustment according to their stage of KD with aMDRD or CG formulae, respectively. CONCLUSION: Systematic estimation of RF with CG or aMDRD formulae and urine dipstick are necessary in RA patients. In patients with KD at high risk for drug toxicity, dosage should be adapted to RF.

Tran TH, Milea D, Cassoux N, Bodaghi B, Bourgeois P, LeHoang P. · Service d'Ophtalmologie, 75013 Paris, France. · J Fr Ophtalmol. · Pubmed #15851955 links to  free full text

Abstract: Infliximab is a chimeric human-murine monoclonal antibody of the IgG1 type with a high affinity and specificity for tumor necrosis factor alpha (TNFalpha). Infliximab was used in Crohn disease, rheumatoid arthritis, spondyloarthropathy, juvenile idiopathic arthritis, Behcet's disease, Wegener's granulomatosis, HLA-B27-associated uveitis and chronic severe refractory uveitis. Reported adverse effects of this treatment were infections, development of antinuclear antibodies and anti double-stranded DNA, lymphomas, and exacerbation of demyelinating disease. We report a case of infliximab-associated optic neuritis with favorable outcome after systemic steroid treatment.

Sany J, Bourgeois P, Saraux A, Durieux S, Lafuma A, Daurès JP, Guillemin F, Sibilia J. · Hôpital Saint Michel, 33 rue Olivier de Serres, 75015 Paris, France. · Ann Rheum Dis. · Pubmed #15361378 links to  free full text

Abstract: OBJECTIVE: To describe the characteristics of rheumatoid arthritis in patients managed by hospital based rheumatologists in France. METHODS: All public and non-profit private hospitals in France were invited to participate in a cross sectional study. Clinical data on the day of inclusion and health resources used for rheumatoid arthritis over the previous 12 months (treatments, medical devices, physician visits, examinations, hospital admissions, and other health professional care) were recorded. RESULTS: 1109 patients from 75 centres located throughout the country were included (846 female; mean disease duration, 10.6 years; mean age, 56.7 years). Active disease (swollen joint count > or =6, tender joint count > or =6, and two of: morning stiffness > or =45 min, C reactive protein > or =20 mg/l, erythrocyte sedimentation rate >28 mm/h) was observed in 146 patients (13.2%). Mean (SD) DAS(28) was 4.51 (1.55). Severe extra-articular manifestations were reported in 8.4%. ACR functional status was: class I, 19%; class II, 28%; class III, 31%; class IV, 22%. Comorbidity was observed in 44.9% of cases, particularly chronic pulmonary disease and coronary or peripheral vascular disease. Average AIMS2-SF dimension scores were between 4.56 and 6.18, and mean HAQ was 1.32 (0.77). Disease modifying antirheumatic drugs (DMARDs) were prescribed for 82.1% of the patients. During the previous four weeks, one DMARD was used in 62.5%, and two or more in 19.5%. Corticosteroids were prescribed in 72%. CONCLUSIONS: In a rheumatoid arthritis population managed by hospital based rheumatologists, the disease was active in 13% and severe in more than one third of cases.

Guillemin F, Durieux S, Daurès JP, Lafuma A, Saraux A, Sibilia J, Bourgeois P, Sany J. · Ecole de Santé Publique, Vandoeuvre-les-Nancy, France. · J Rheumatol. · Pubmed #15229947 No free full text.

Abstract: OBJECTIVE: The economic impact of rheumatoid arthritis (RA) is substantial, but most studies provide cost estimates specific to a US population. We performed a cost-of-illness analysis of patients with RA for French society. METHODS: A cross-sectional study among rheumatologists in 148 hospitals in France was conducted between November and December 2000. Data were collected on health resource consumption associated with RA (treatments, medical devices, physician visits, examinations, hospitalization, other health professional care) during the previous 12 months. Direct costs and social costs were evaluated for 1109 RA patients. The relation of costs to disease activity and severity was analyzed. RESULTS: The annual direct cost of RA per patient was over euro4000. The costs due to hospitalizations represented around 60% of the costs. The major reason for hospitalization was acute care for RA in a rheumatic disease ward. Patients visited a physician an average of 13 times during the 12 months, 7.7 +/- 8.6 visits to an office-based physician and 5.1 +/- 4.4 visits to a hospital-based physician. Among them, 37% of patients were receiving at least one disability pension (16.7%) or sick-leave allowance (11.9%), with an estimated cost of euro7328 per patient. The mean annual budget per patient was euro2742. Medical and social costs increased in patients with severe disease (2 times), longer disease duration since diagnosis (more than double for patients with a history longer than 10 yrs vs patients with less than 2 yrs), active disease (1.4 times), and functional status (4 times more for American College of Rheumatology class IV than for class I). CONCLUSION: Direct costs represented 59% of the total costs for patients with active RA and 57% for patients with severe RA. Social costs represented 41% of the total costs on average.

Fautrel B, Zing E, Golmard JL, Le Moel G, Bissery A, Rioux C, Rozenberg S, Piette JC, Bourgeois P. · Department of Rheumatology, Pitié-Salpêtrière Hospital, Paris, France. · Medicine (Baltimore). · Pubmed #11997716 No free full text.

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Fautrel B, Le Moël G, Saint-Marcoux B, Taupin P, Vignes S, Rozenberg S, Koeger AC, Meyer O, Guillevin L, Piette JC, Bourgeois P. · Department of Rheumatology, Pitié-Salpêtrière Hospital, Paris, France. · J Rheumatol. · Pubmed #11246670 No free full text.

Abstract: OBJECTIVE: To determine the usefulness of serum ferritin and glycosylated ferritin (GF) levels in diagnosing adult onset Still's disease (AOSD). METHODS: We performed a retrospective multicenter study of 205 patients who had ferritin and GF assays in one hospital laboratory. Records of all patients were reviewed, and a standardized questionnaire used to extract all data available at the time of the assay. The clinicians' final diagnosis was also recorded. Patients were classified as having "certain AOSD" (based on Yamaguchi's criteria) or a control disease. The concordance of ferritin and GF levels with final diagnosis was evaluated. RESULTS: In total 49 AOSD and 120 control patients were eligible. The mean ferritin value was significantly higher in the AOSD group (4,752 +/- 9,599 microg/l) than in the control group (1,571 +/- 3,807 microg/l), p = 0.029. GF was significantly lower in AOSD patients (15.9 +/- 11.9%) than in the control group (31.5 +/- 18.7%), p < 0.001. The combination of a GF level of < or = 20% with ferritin above the upper limit of normal yielded a sensitivity of 70.5% and specificity of 83.2%. The combination of a GF level < or = 20% with ferritin 5 times normal produced a sensitivity of 43.2% and specificity of 92.9%. This latter combination allowed an AOSD diagnosis to be ruled out for 6 of the 8 control patients who met Yamaguchi's positive criteria. CONCLUSION: Ferritin and GF levels are powerful diagnostic markers of AOSD. They may be helpful in clinical practice for excluding differential diagnoses.

Durieux S, Rozenberg S, Bourgeois P. · Service de rhumatologie, hôpital de la Pitié-Salpêtrière, Paris, France. · Rev Med Interne. · Pubmed #10220819 No free full text.

Abstract: INTRODUCTION: Among the gastrointestinal adverse effects of nonsteroidal anti-inflammatory drugs (NSAID) and corticoids are mentioned complications of colonic diverticular disease. However, very few studies have described their consequences in rheumatoid arthritis. EXEGESIS: We report on seven patients who were admitted in our department between 1984 and 1997. All patients received corticoids and another antirheumatic drug (gold salts, hydroxychloroquine, immunosuppressive drugs); treatment also included NSAID in four cases. Two patients had a necrotizing vasculitis accompanying rheumatoid arthritis. Intestinal accompanying diseases were the following: one diverticulitis, three colonic perforations with pelviperitonitis, one colovesical fistula, one pelvic abscess, and one diverticular hemorrhage. All patients underwent surgery with positive results. CONCLUSION: Combination of the four following symptoms: fever, abdominal pain, diarrhea, and hemorrhage, can uncover a complication of colónic diverticular disease occurring in the course of rheumatoid arthritis. It should be investigated, even if no history of diverculosis may be evidenced.

Foltz V, Loeuille D, Etchepare F, Chary-Valckenaere I, Rosenberg C, Tanguy ML, Fautrel B, Bourgeois P. · No affiliation provided · Joint Bone Spine. · Pubmed #18945634 No free full text.

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Banal F, Etchepare F, Rouhier B, Rosenberg C, Foltz V, Rozenberg S, Koeger AC, Fautrel B, Bourgeois P. · No affiliation provided · Ann Rheum Dis. · Pubmed #16769791 links to  free full text

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Fautrel B, Foltz V, Frances C, Bourgeois P, Rozenberg S. · No affiliation provided · Arthritis Rheum. · Pubmed #12115253 links to  free full text

This publication has no abstract.