T Papo

Paris Diderot University, Lutetia Parisorum, Île-de-France, France

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Publications (366)1265.13 Total impact

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    ABSTRACT: Cardiovascular disease due to accelerated atherosclerosis is the leading cause of death in patients with systemic lupus erythematosus (SLE). Noteworthy, accelerated atherosclerosis in SLE patients appears to be independant of classical Framingham risk factors. This suggests that aggravated atherosclerosis in SLE patients may be a result of increased inflammation and altered immune responses. However, the mechanisms that mediate the acceleration of atherosclerosis in SLE remain elusive. Based on experimental data which includes both humans (SLE patients and control subjects) and rodents (ApoE-/- mice), we herein propose a multi-step model in which the immune dysfunction associated with SLE (i.e. high level of IFN-α production by TLR 9-stimulated pDCs) is associated with, first, an increased frequency of circulating pro inflammatory CD4+CXCR3+ T cells; second, an increased production of CXCR3 ligands by endothelial cells; third, an increased recruitment of pro-inflammatory CD4+CXCR3+ T cells into the arterial wall, and fourth, the development of atherosclerosis. In showing how SLE may promote accelerated atherosclerosis, our model also points to hypotheses for potential interventions, such as pDCs-targeted therapy, that might be studied in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Journal of Autoimmunity 07/2015; 63. DOI:10.1016/j.jaut.2015.07.001 · 8.41 Impact Factor
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    ABSTRACT: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab). Copyright © 2015 Elsevier Ltd. All rights reserved.
    Journal of Autoimmunity 07/2015; 62. DOI:10.1016/j.jaut.2015.06.005 · 8.41 Impact Factor
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    ABSTRACT: Background Cardiovascular disease (CVD) is a major cause of death in systemic lupus erythematosus (SLE) patients. Obesity is an additional risk factor for cardiovascular disease that appears to be more prevalent in SLE population Objectives We aimed to determine whether overweight (defined as a BMI>25) contributed to subclinical atherosclerosis in SLE patients at low risk for CVD according to traditional factors. Methods Internal carotid wall thickness (ICWT) and carotid plaques were prospectively assessed, as a measure of subclinical atherosclerosis, in 49 SLE patients asymptomatic for CVD and 49 controls matched on Framingham score. Factors associated to ICWT were identified in SLE patients and in controls and multiple linear regression (multivariate analysis) was performed. Results SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (mean 1.9±3.5 in SLE vs 1.8±3.2% in controls, p=0.37). ICWT (1.3±0.6 vs 1±0.3mm, p=0.0007) and number of patients with carotid plaques (18.4% vs 2.0%, p=0.015) were however higher in SLE patients as compared to controls. In multivariable analysis, SLE was an independent the risk for a carotid plaque (OR [95%CI]: 3.53 [1.36 - 9.14]; p=0.009 as compared to controls). Older age, higher body mass index (BMI) and higher Framingham score were associated with atherosclerosis in SLE patients in univariate analysis. In multivariate analysis, only the association with overweight (i.e. BMI>25kg/m2) remained significant (OR [95%CI]: 4.13 [1.02 - 16.75]; p=0.047). Conclusions Overweight is an independent contributor to atherosclerosis in systemic lupus erythematosus. Identifying SLE patients at a higher risk for CVD is mandatory. Body weight control should be a specific target in clinical practice in order to prevent the occurrence of atherosclerosis and its deleterious consequences in patients with SLE. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):948.3-949. DOI:10.1136/annrheumdis-2015-eular.1082 · 10.38 Impact Factor
  • N. Chavarot · M. Hourseau · T. Papo · K. Sacre
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):643.1-643. DOI:10.1136/annrheumdis-2015-eular.1080 · 10.38 Impact Factor
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    ABSTRACT: Background IgG4-related disease (IgG4-RD) is a recently recognized systemic condition characterized by unique pathological features that affect a wide variety of organs. Most available data come from descriptive series of patients with a unique organ involvement. Objectives To describe clinical and biological characteristics of IgG4-RD patients from a large multicentric national registry. Methods Cases were collected through a multicentric and multidisciplinary national registry between 2009 and 2014. Data were collected using a standardized form including clinical, biological, pathological and therapeutic findings. Results From 120 collected cases, 90 cases fulfilled comprehensive diagnostic criteria for IgG4-RD [1]. Patients presented with definite (44.5%), probable (24.4%) and possible (31.1%) IgG4-RD diagnosis. They were 64 males and 26 females (sex ratio 2.5:1) with a median age at onset of 56 years. Ninety-three percent of patients presented with symptoms at diagnosis, including constitutional symptoms (45%), abdominal pain (26%), cough or dyspnea (17%) and sicca syndrome (15%). Median number of organs involved was 3 and 80% of patients had multi-organ involvement, defined by ≥3 organs involved. Lymph nodes (58.9%), pancreas (44.4%), kidney (32.2%), salivary glands (32.2%), retroperitoneum (28.9%) and biliary ducts (27.8%) were the most frequent tissues involved. Inflammatory pseudotumors (IPT) were observed in 30% of patients (pulmonary, orbital, hepatic, meningeal or breast IPT). IgG4 serum concentration was >135 mg/dl in 84% of patients, with a mean of 989 mg/dl (ranging from 30 to 5380). Polyclonal hypergammaglobulinemia was noted in 79% of cases, and low complement in 34%. Elevated C reactive protein level was observed in 48% of patients. Mean follow-up was 17.6 months (ranging from 0 to 94). Only ten patients (11%) did not require systemic therapy. Seventy-seven patients (86%) received steroids in first line therapy. A second line therapy was required in 36 patients (40%), with 20 patients treated with 3 lines of treatment or more. Indications of second line treatments were essentially represented by relapse or corticodependance. Second line treatments were azathioprine in 14 patients, rituximab in 10, mycophenolate mofetil in 3, cyclophosphamide in 3 and methotrexate in 2. Six patients underwent surgery, essentially for histological diagnosis because cancer was suspected. Conclusions As described in Asiatic populations, most IgG4-RD patients from our national registry present with multiple organ involvement. Localized disease is less frequent. Normal IgG4 levels are observed in 16% of patients. Steroids are usually effective, but almost half of patients require second line immunosuppressive therapy as steroid sparing agent or for relapse. References Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):857.1-857. DOI:10.1136/annrheumdis-2015-eular.5597 · 10.38 Impact Factor
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    ABSTRACT: Tracheobronchial stenosis (TBS) is noted in 12-23% of patients with granulomatosis with polyangiitis (GPA), and includes subglottic stenosis and bronchial stenosis. We aimed to analyse the endoscopic management of TBS in GPA and to identify factors associated with the efficacy of endoscopic interventions. We conducted a French nationwide retrospective study that included 47 patients with GPA-related TBS. Compared with patients without TBS, those with TBS were younger, more frequently female and had less frequent kidney, ocular and gastrointestinal involvement and mononeuritis multiplex. Endoscopic procedures included 137 tracheal and 50 bronchial interventions, mainly endoscopic dilatation, local steroid injection and conservative laser surgery, and less frequently stenting. After the first endoscopic procedure, the cumulative incidence of endoscopic treatment failure was 49% at 1 year, 70% at 2 years and 80% at 5 years. Factors significantly associated with a higher cumulative incidence of treatment failure were a shorter time from GPA diagnosis to endoscopic procedure [hazard ratio (HR) 1.08 (95% CI 1.01, 1.14); P = 0.01] and a bronchial stenosis [HR 1.96 (95% CI 1.28, 3.00); P = 0.002]. A prednisone dose ≥30 mg/day at the time of the procedure was associated with a lower cumulative incidence of treatment failure [HR 0.53 (95% CI 0.31, 0.89); P = 0.02]. TBS represents severe and refractory manifestations with a high rate of restenosis. High-dose systemic CSs at the time of the procedure and increased time from GPA diagnosis to bronchoscopic intervention are associated with a better event-free survival. In contrast, bronchial stenoses are associated with a higher rate of restenosis than subglottic stenosis. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Rheumatology (Oxford, England) 05/2015; 54(10). DOI:10.1093/rheumatology/kev129 · 4.48 Impact Factor
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    ABSTRACT: Systemic rheumatic diseases (SRD) patients may require ICU management for SRD exacerbation, treatment-related infectious or toxicities. Observational study in 10 university-affiliated ICUs in France. Consecutive patients with SRD were included. Determinants of ICU mortality were identified through multivariable logistic analysis. 363 patients (65.3 % women, median age 59y (IQR, 42-70)) accounted for 381 admissions. Connective tissue disease (primarily Systemic Lupus Erythematosus) accounted for 66.1% of SRD and systemic vasculitides for 26.2 % (chiefly ANCA-associated vasculitides). SRD was newly diagnosed in 43 (11.3%) cases. Direct admission to ICU occurred in 143 (37.9%) cases. Reasons for ICU admissions were infection (39.9%), SRD exacerbation (34.4%), toxicity (5.8 %) or miscellaneous (19.9%). Respiratory involvement was the leading cause of admission (56.8 %), followed by shock (41.5 %) and acute kidney injury (42.2%). Median SOFA on day-1 was 5 [3-8]. Mechanical ventilation was required in 57% cases, vasopressors in 33.9% and renal replacement therapy in 28.1%. ICU mortality rate was 21.0% (80 deaths). Factors associated with ICU mortality were shock (OR: 3.77 [95%CI, 1.93 -7.36]), SOFA score at day 1 (OR: 1.19 [95%CI, 1.10-1.30]) and direct admission (OR: 0.52, [CI 0.28-0.97]. Neither comorbidities nor SRD characteristics were associated with survival. In SRD patients, critical care management is mostly needed in patients with previously known SRD; still, diagnosis can be made in the ICU in 12% of the patients. Infection and SRD exacerbation account for more than two-third of the situations, both targeting chiefly the lungs. Direct admission to the ICU might improve outcomes.
    Chest 05/2015; DOI:10.1378/chest.14-3098 · 7.48 Impact Factor
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    ABSTRACT: The blood hydroxychloroquine concentration varies widely among patients with systemic lupus erythematosus (SLE): a pharmacokinetic/pharmacodynamic relation has been found in different situations, and very low blood HCQ concentration is a simple marker of non-adherence to treatment. Therefore, the interest in blood HCQ concentration measurement has increased, but little is known about factors influencing blood HCQ concentration variability. Retrospective analyses of data for patients, including from the Plaquenil LUpus Systemic (PLUS) study, to determine the association of epidemiological, clinical and biological factors and blood HCQ concentration. Data for non-adherent patients (blood HCQ concentration <200 ng/ml) were excluded. To examine homogeneous pharmacological data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking and blood HCQ concentration and no pharmacokinetic drug-drug interaction with antiacids or inhibitors and inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (p=0.008), no treatment with corticosteroids (p=0.04), increased delay between the last tablet intake and measurement of blood HCQ concentration (p=0.017), low platelet (p<0.001) and neutrophil (p<0.001) counts, and high estimated creatinine clearance (p<0.001) were associated with low blood HCQ concentration. For 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 [range: 23-58] ml/min) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than for the 509 patients from the PLUS study: 1338 [range: 504-2229] ng/ml versus 917 [208-3316] ng/ml (p<0.001). We provide a comprehensive analysis of determinants of blood HCQ concentration. Because this measurement is increasingly being used, these data might be useful for clinicians. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    Arthritis and Rheumatology 05/2015; 67(8). DOI:10.1002/art.39194
  • T. Papo
    03/2015; 17(1). DOI:10.1016/S1634-7358(15)69858-8
  • Clinical and experimental rheumatology 01/2015; 33(1). · 2.72 Impact Factor
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    ABSTRACT: Abstract Background: In published case reports, tocilizumab (TCZ) has shown good efficacy for AA amyloidosis in almost all patients. We investigated the efficacy and safety of TCZ in AA amyloidosis in a multicentre study of unselected cases. Methods: We e-mailed rheumatology and internal medicine departments in France, Switzerland and North Africa by using the Club Rhumatismes Inflammation (CRI) network and the French TCZ registry, Registry RoAcTEmra (REGATE), to gather data on consecutive patients with histologically proven AA amyloidosis who had received at least one TCZ infusion. Efficacy was defined as a sustained decrease in proteinuria level and/or stable or improved glomerular filtration rate (GFR) and by TCZ maintenance. Results: We collected 12 cases of AA amyloidosis treated with TCZ as monotherapy (mean age of patients 63 ± 16.2 years, amyloidosis duration 20.6 ± 31.3 months): eight patients had rheumatoid arthritis (RA), six with previous failure of anti-tumor necrosis factor α (anti-TNF-α) therapy. In total, 11 patients had renal involvement, with two already on hemodialysis (not included in the renal efficacy assessment). For the nine other patients, baseline GFR and proteinuria level were 53.6 ± 32.8 mL/min and 5 ± 3.3 g/24 h, respectively. The mean follow-up was 13.1 ± 11 months. TCZ was effective for six of the eight RA patients (87.5%) according to European League Against Rheumatism response criteria (four good and two moderate responders). As expected, C-reactive protein (CRP) level decreased with treatment for 11 patients. Renal amyloidosis (n = 9) progressed in three patients and was stabilized in three. Overall, three patients showed improvement, with sustained decrease in proteinuria level (42%, 82% and 96%). Baseline CRP level was higher in subsequent responders to TCZ than other patients (p = 0.02). Among the six RA patients with previous anti-TNF-α therapy, amyloidosis was ameliorated in one and stabilized in three. Three serious adverse events occurred (two diverticulitis and one major calciphylaxia due to renal failure). Finally, 7 of 12 (58%) patients continued TCZ. Conclusions: The efficacy of TCZ for AA amyloidosis varies depending on the inflammatory status at treatment onset. Discrepancies between our study of unselected consecutive patients and reported cases may be due to publication bias. These results support further prospective trials of TCZ for AA amyloidosis.
    Amyloid 01/2015; 22(2):1-9. DOI:10.3109/13506129.2014.1002031 · 2.01 Impact Factor
  • La Revue de Médecine Interne 12/2014; 35. DOI:10.1016/j.revmed.2014.10.026 · 1.07 Impact Factor
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    ABSTRACT: Background Giant cell arteritis (GCA) is the most frequent vasculitis in patients aged over 50 years old in Europe and North America. Stroke may occur in patients with GCA. In most cases, stroke is related to vasculitis of extracranial cerebral arteries causing vertebral or internal carotid arteries stenosis. However cerebrovascular accidents are rare in the setting of GCA and specific involvement of cranial arteries may be difficult to distinguish from non-specific atherosclerotic lesions in the elderly Objectives The aim of our study was to highlight the clinical spectrum and long-term follow-up of GCA-specific stroke. Methods Medical charts of all patients followed in a French department of internal medicine for GCA between January 2008 and January 2014 were retrospectively reviewed. Patients with cerebrovascular accidents at GCA diagnosis were included. Diagnosis of GCA was based on American College of Rheumatology criteria. Transient ischemic attacks and stroke resulting from an atherosclerotic or cardioembolic mechanism were excluded. Clinical features, GCA-diagnosis workup, brain imaging, cerebrospinal fluid (CSF) study, treatment, and follow-up data were analysed. Results From January 2008 to January 2014, 97 patients have been followed for GCA. Among them, 8 biopsy-proven GCA patients (mean age 70±7.8 years, M/F Sex ratio 3/1) had stroke at GCA diagnosis. Six patients reported headache and visual impairment. Brain MR angiography showed involvement of vertebral and/or basilar arteries in all cases with multiple or unique ischemic lesions in the infratentorial region of the brain in all but one case. Intracranial cerebral arteries involvement was observed in 4 cases including 2 cases with cerebral angiitis. Long lasting lesions on diffusion-weight brain MRI sequences were observed in 1 case. All patients received steroids for a mean of 28.1±12.8 months. Side effects associated with long-term steroid therapy occurred in six patients. Relapses occurred in 4 patients and required immunosuppressive drugs in 3 cases. After a mean follow-up duration of 36.4±16.4 months, all but one patient achieved complete remission without major sequelae. Conclusions The conjunction of headache with vertebral and basilar arteries involvement in elderly is highly suggestive of stroke associated with GCA. Intracranial cerebral arteries involvement with cerebral angiitis associated with long lasting brain lesions on diffusion-weight brain MRI sequences may occur in GCA. Both frequent relapses and steroid-induced side effects argue for the use of immunosuppressive agents combined with steroids as first-line therapy. Disclosure of Interest None declared
    Medicine 12/2014; 93(28):e265. DOI:10.1097/MD.0000000000000265 · 5.72 Impact Factor
  • T. Papo
    11/2014; 18(4). DOI:10.1016/S1636-5410(14)69215-1
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Publication Stats

3k Citations
1,265.13 Total Impact Points


  • 2008–2015
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 2003–2015
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      • Service de Médecine Interne
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Centre Hospitalier Universitaire d'Angers
      Angers, Pays de la Loire, France
  • 2008–2011
    • Assistance Publique – Hôpitaux de Paris
      • Département de Médecine Interne
      Lutetia Parisorum, Île-de-France, France
  • 2010
    • American Hospital of Paris
      Lutetia Parisorum, Île-de-France, France
  • 2009–2010
    • University of Paris-Est
      La Haye-Descartes, Centre, France
  • 1997–2007
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
  • 1990–2007
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • Service de Médecine Interne 1
      Lutetia Parisorum, Île-de-France, France
  • 1998
    • Hôpital de Poissy Saint Germain en Laye
      Saint-Germain, Île-de-France, France