Raphaèle Seror

Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre, Lutetia Parisorum, Île-de-France, France

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Publications (139)

  • Raphaèle Seror · Divi Cornec
    Book · Jun 2016
  • A. Mirouse · R. Seror · X. Mariette · [...] · D. Dumont-Fischer
    Article · Jun 2016
  • Gaetane Nocturne · Divi Cornec · Raphaèle Seror · Xavier Mariette
    Article · Jun 2016 · Rheumatic Disease Clinics of North America
  • Raphaèle Seror · Divi Cornec
    Chapter · Jun 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives: To identify the principal determinants of health-related quality-of-life [HR-QoL] impairment in patients with active primary Sjögren's syndrome [pSS] participating in a large therapeutic trial [TEARS]. Methods: At the inclusion visit for the TEARS trial, 120 patients with active pSS completed the Short Form survey 36 [SF36], a validated HR-QoL assessment tool. Univariate then multivariate linear regression analyses were used to assess associations linking SF36 physical and mental components to demographic data, patient-reported outcomes [symptom intensity assessments for dryness, pain and fatigue, including the EULAR SS Patient Reported Index (ESSPRI)], objective measures of dryness and autoimmunity, and physician evaluation of systemic activity [using the EULAR SS Disease Activity Index (ESSDAI)]. Results: SF36 scores indicated marked HR-QoL impairments in our population with active pSS. Approximately 1/3 of the patients had low, moderate and high systemic activity according to the ESSDAI. ESSPRI and ESSDAI scores were moderately but significantly correlated. The factors most strongly associated with HR-QoL impairment were patient-reported symptoms, best assessed using the ESSPRI, with pain and ocular dryness intensity showing independent associations with HR-QoL. Conversely, systemic activity level was not associated with HR-QoL impairment in multivariate analyses, even in the patient subset with ESSDAI values indicating moderate-to-high systemic activity. Conclusions: The cardinal symptoms of pSS (dryness, pain and fatigue, best assessed using the ESSPRI) are stronger predictors of HR-QoL impairment than systemic involvement (assessed by the ESSDAI), and should be used as endpoints in future therapeutic trials focusing on patients' well-being. New consensual and data-driven response criteria are needed for pSS studies. This article is protected by copyright. All rights reserved.
    Article · Jun 2016
  • F. Danion · N. Rosine · R. Belkhir · [...] · R. Seror
    [Show abstract] [Hide abstract] ABSTRACT: Objective: The objective of this study was to assess the safety and efficacy of abatacept in patients with SLE refractory to conventional treatment in routine clinical practice. Methods: This retrospective study included 11 SLE patients treated with abatacept for an active and refractory disease. The primary endpoint was the change in SLE Disease Activity Index (SLEDAI) score at six months. Response was defined as a decrease of SLEDAI ≥4 in a patient continuing abatacept. Results: Indications of abatacept treatment were articular (n=8), renal (n=1) and cutaneous (n=1) involvement and autoimmune thrombocytopenia (n=1). Abatacept was discontinued before six months in two patients, because of adverse event (n=1) and/or lupus flare (n=2). The median SLEDAI decreased from 6 (2-20) to 4 (0-20) (p=0.031). Decrease of SLEDAI ≥4 was observed in 6/11 patients (55%) and response to treatment according to the physician's judgement in 8/11 (73%) patients. Improvement of articular involvement was observed in 7/8 (87.5%) patients. Four adverse events were observed in three patients, but no severe infection occurred. Conclusion: This study suggests some efficacy of abatacept in patients with refractory disease in routine clinical practice, particularly in the case of articular manifestations, with an acceptable safety profile. These data support conducting new controlled trials of abatacept in SLE patients.
    Article · Mar 2016 · Lupus
  • Gaetane Nocturne · Divi Cornec · Raphaèle Seror · Xavier Mariette
    [Show abstract] [Hide abstract] ABSTRACT: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by dryness and systemic involvement in more than a third of the patients. Patient management has suffered from the lack of effective treatments. However, progresses made in the understanding of pSS pathogenesis have allowed a move to a more targeted approach to therapeutic intervention. Given the key role of chronic B cell activation, B cell-targeted therapies were the first candidate. New pathways are currently investigated including costimulation and ectopic germinal centre formation. In this review, we have summarized the new tools available in clinical research in the field of pSS, the current evidence regarding B cell-targeted therapies and an overview of the promising drugs in the pipeline.
    Article · Mar 2016 · Best practice & research. Clinical rheumatology
  • [Show abstract] [Hide abstract] ABSTRACT: There is convincing evidence for the known and unambiguously accepted beneficial effects of glucocorticoids at low dosages. However, the implementation of existing recommendations and guidelines on the management of glucocorticoid therapy in rheumatic diseases is lagging behind. As a first step to improve implementation, we aimed at defining conditions under which long-term glucocorticoid therapy may have an acceptably low level of harm. A multidisciplinary European League Against Rheumatism task force group of experts including patients with rheumatic diseases was assembled. After a systematic literature search, breakout groups critically reviewed the evidence on the four most worrisome adverse effects of glucocorticoid therapy (osteoporosis, hyperglycaemia/diabetes mellitus, cardiovascular diseases and infections) and presented their results to the other group members following a structured questionnaire for final discussion and consensus finding. Robust evidence on the risk of harm of long-term glucocorticoid therapy was often lacking since relevant study results were often either missing, contradictory or carried a high risk of bias. The group agreed that the risk of harm is low for the majority of patients at long-term dosages of ≤5 mg prednisone equivalent per day, whereas at dosages of >10 mg/day the risk of harm is elevated. At dosages between >5 and ≤10 mg/day, patient-specific characteristics (protective and risk factors) determine the risk of harm. The level of harm of glucocorticoids depends on both dose and patient-specific parameters. General and glucocorticoid-associated risk factors and protective factors such as a healthy lifestyle should be taken into account when evaluating the actual and future risk.
    Article · Mar 2016 · Annals of the Rheumatic Diseases
  • Raphaèle Seror · Petra Meiners · Gabriel Baron · [...] · Cristina Vollenweider
    [Show abstract] [Hide abstract] ABSTRACT: Objective To develop and validate ClinESSDAI (Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index), ie, ESSDAI without the biological domain. Patients and methods The 702 fictive vignettes derived from 96 real cases of primary Sjögren's syndrome of the ESSDAI development study were used. As for ESSDAI development, the physician assessment of disease activity (0–10 scale) was used as the ‘gold standard’ in a multivariate model for weighting domains, after removing the biological domain. The reliability, assessed by intraclass correlation coefficient (ICC) between ClinESSDAI and ESSDAI, explored if ClinESSDAI was equivalent to ESSDAI. Its psychometric (ie, measurement) properties were compared with that of ESSDAI in an independent cohort. Also, its use was evaluated on data of two clinical trials. Results In multivariate modelling, all 11 domains remained significantly associated with disease activity, with slight modifications of some domain weights. Reliability between clinESSDAI and ESSDAI was excellent (ICC=0.98 and 0.99). Psychometric properties of clinESSDAI, disease activity levels and minimal clinically important improvement thresholds and its ability to detect change over time in clinical trials were very close to that of ESSDAI. Conclusions ClinESSDAI appears valid and very close to the original ESSDAI. This score provides an accurate evaluation of disease activity independent of B-cell biomarkers. It could be used in various circumstances: (i) in biological/clinical studies to avoid data collinearity, (ii) in clinical trials, as secondary endpoint, to detect change independent of biological effect of the drug, (iii) in clinical practice to assess disease activity for visits where immunological tests have not been done.
    Article · Jan 2016 · Annals of the Rheumatic Diseases
  • Source
    Raphaèle Seror · Saida Boudaoud · Stephan Pavy · [...] · Corinne Miceli-Richard
    [Show abstract] [Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic condition over the world. RA is potentially disabling because chronic inflammation of the joints leads to joint destruction. To date, the best predictor of radiographic progression for patients with early RA is the presence of radiographic erosions at baseline, but a limited number of predictive biomarkers of structural progression are currently used in daily practice. Here, we investigated Dickkopf-1 (DKK-1) and sclerostin (SOST) serum levels in patients with recent inflammatory arthritis from the ESPOIR cohort. This cohort is a prospective, multicenter French cohort of 813 patients with early arthritis. We observed that mean baseline DKK-1 level was higher among RA patients with than without radiological progression within the first 2 years of evolution. DKK-1 level was still associated with radiographic progression in a model including other main predictors of severity (erosions at baseline, and anti-CCP antibody positivity). This study demonstrates that increased DKK-1 level at baseline predicted structural progression after 2-year follow-up and suggests that DKK-1 might be a new structural biomarker for early RA.
    Full-text Article · Jan 2016 · Scientific Reports
  • Gaetane Nocturne · Raphaèle Seror · Xavier Mariette
    Article · Jan 2016 · Arthritis and Rheumatology
  • Source
    Full-text Dataset · Jan 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Sjögren's syndrome (SjS) is a systemic autoimmune disease that mainly affects the exocrine glands, leading to generalized mucosal dryness. However, primary SjS may initially present with non-sicca (systemic) manifestations. When these features appear before the onset of an overt sicca syndrome, we may talk of an underlying 'occult' SjS. The European League Against Rheumatism (EULAR) has promoted and supported an international collaborative study group (EULAR-SS Task Force) aimed at developing consensual recommendations to provide a homogeneous approach to the patient with primary SjS presenting with systemic involvement. This review summarizes the key factors that should be taken into account in the diagnostic approach in a patient with suspected SjS according to the main clinical patterns of presentation, and is especially focused on organ-specific systemic disease presentations, including a consensus set of recommendations in order to reach an early diagnosis. Close collaboration with the different specialties involved through a comprehensive multidisciplinary approach is essential in SjS patients presenting with systemic involvements.
    Article · Dec 2015 · Expert Review of Clinical Immunology
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (pSS). Methods: A multicenter case-controls survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after pSS diagnosis. They were mainly recruited through the "Club Rhumatismes et Inflammation" network. For each case, 2 controls (matched on disease duration and age) were randomly selected among patients without lymphoma. Cases and controls were compared with univariate then multivariate analysis to identify independent predictors of lymphoma. Results: One hundred and one pSS patients with lymphoma were included; 87 were women (86.1%) with a mean age ± SD of 57.4 ±12.6 years. Histologic type was B cell non Hodgkin lymphoma (B-NHL) in 99/101 with 76 (76.8%) marginal zone including 58 (58.6%) developed from the Mucosa associated lymphoid tissue (MALT). The most frequent localization was salivary glands (43 cases). A specific treatment was initiated at diagnosis in 87/99 patients with B-NHL and remission was obtained in 61 patients (61.6%). In the multivariate analysis salivary gland enlargement, rheumatoid factor, low C4, cryoglobulinemia, lymphopenia and disease activity (excluding the lymphoma domain) were found predictors of lymphoma. We did not find any role of previous treatments of pSS for preventing or favoring lymphoma occurrence. Conclusion: In addition to previous known predictive factors of lymphoma occurrence, this case-control study of pSS-associated lymphoma demonstrated the independent role of rheumatoid factor and of disease activity. It highlights the role of chronic antigenic stimulation and disease activity in the development of this severe complication. This article is protected by copyright. All rights reserved.
    Article · Nov 2015 · Arthritis and Rheumatology
  • Anne-Laurence Tomi · Rakiba Belkhir · Gaétane Nocturne · [...] · Raphaèle SEROR
    [Show abstract] [Hide abstract] ABSTRACT: Objective To assess the link between monoclonal gammopathy (MG), disease activity, and incidence of malignant hematologic disorders (MHDs), including lymphoma and multiple myeloma (MM), in patients with primary Sjögren's syndrome (SS). Methods Screening for the presence of MG was performed in 352 primary SS patients. Each patient with MG was paired with 2 age- and sex-matched primary SS controls without MG. Their characteristics were compared for the presence of risk factors for MG and for the relationship between MG and MHD. Results Twenty-six of the 352 primary SS patients (7.4%) had MG; 88% were women, with a median age of 62.7 years (interquartile range [IQR] 50.3-69.1 years) and a median disease duration of 7.8 years (IQR 3.6-12.8 years). The parameters associated with MG on multivariate analysis were higher disease activity, as measured by either the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI; adjusted odds ratio [OR] 9.7, P = 0.0002) or the Clinical ESSDAI (adjusted OR 6.7, P = 0.001), and low C4 level (adjusted OR 3.4, P = 0.04). After a median follow-up of 6.3 years (IQR 3.1-9.5 years), 10 patients with MG had developed an MHD (38.5%; 4 had lymphomas and 6 had MM), as compared with 4 patients in the control group (7.7%; all had lymphomas) (OR 7.5, P = 0.002). The only factor associated with the risk of MHDs was the presence of MG (adjusted OR 5.5, P = 0.02), which was principally associated with an increased risk of MM (23% versus 0%; P = 0.0009), but not lymphoma (15% versus 8%; P = 0.3). Conclusion The presence of MG was associated with higher disease activity and an increased risk of MHD in primary SS. In the presence of MG, the risk of MM was even higher than the risk of lymphoma. These results suggest that regular monitoring of primary SS patients with MG for the emergence of both lymphoma and MM is necessary.
    Article · Nov 2015 · Arthritis and Rheumatology
  • Article · Oct 2015 · Rheumatology (Oxford, England)
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    [Show abstract] [Hide abstract] ABSTRACT: Objective: The goal of this study was to determine how the choice of the primary endpoint influenced sample size estimates in randomised controlled trials (RCTs) of treatments for primary Sjögren's syndrome (pSS). Methods: We reviewed all studies evaluating biotechnological therapies in pSS to identify their inclusion criteria and primary endpoints. Then, in a large cohort (ASSESS), we determined the proportion of patients who would be included in RCTs using various inclusion criteria sets. Finally, we used the population of a large randomised therapeutic trial in pSS (TEARS) to assess the impact of various primary objectives and endpoints on estimated sample sizes. These analyses were performed only for the endpoints indicating greater efficacy of rituximab compared to the placebo. Results: We identified 18 studies. The most common inclusion criteria were short disease duration; systemic involvement; high mean visual analogue scale (VAS) scores for dryness, pain, and fatigue; and biological evidence of activity. In the ASSESS cohort, 35 percent of patients had recent-onset disease (lower than 4 years), 68 percent systemic manifestations, 68 percent high scores on two of three VASs, and 52 percent biological evidence of activity. The primary endpoints associated with the smallest sample sizes (nlower than 200) were a VAS dryness score improvement higher to 20 mm by week 24 or variable improvements (10, 20, or 30 mm) in fatigue VAS by week 6 or 16. For patients with systemic manifestations, the ESSDAI change may be the most logical endpoint, as it reflects all domains of disease activity. However, the ESSDAI did not improve significantly with rituximab therapy in the TEARS study. Ultrasound score improvement produced the smallest sample size estimate in the TEARS study. Conclusion: This study provides valuable information for designing future RCTs on the basis of previously published studies. Previous RCTs used inclusion criteria that selected a small part of the entire pSS population. The endpoint was usually based on VASs assessing patient complaints. In contrast to VAS dryness cut-offs, VAS fatigue cut-offs did not affect estimated sample sizes. SGUS improvement produced the smallest estimated sample size. Further studies are required to validate standardised SGUS modalities and assessment criteria. Thus, researchers should strive to develop a composite primary endpoint and to determine its best cut-off and assessment time point.
    Full-text Article · Sep 2015 · PLoS ONE
  • Candice Estellat · Florence Tubach · Raphaèle Seror · [...] · Philippe Ravaud
    [Show abstract] [Hide abstract] ABSTRACT: Background: Control treatments in randomized controlled trials (RCTs) should not deliberately disadvantage patients. Objectives: To compare (a) willingness to include versus (b) willingness to prescribe control treatment among physicians randomized to assess, respectively, either (a) enrollment in a trial or (b) appropriateness of control treatment in a care context for the same fictional patient. Participants: Physicians were authors of articles about rheumatoid arthritis (RA), involved in RA patient care and used to enrolling patients in trials. Outcomes: Willingness to give control treatment: trial enrollment or control-treatment appropriateness in care context. Methods: We derived 3 case vignettes of fictional standard eligible patients for each of 30 RCTs assessing biologics in RA. Physicians were randomly allocated to the "trial" or "care" arm. For each of the 90 fictional patients, physicians assigned to the trial arm were asked if they would enroll the patient in the RCT the patient was derived from. For the same 90 fictional patients, physicians assigned to the care arm were asked if the control treatment of the RCT was appropriate in a context of usual care. Results: Of the 1,779 physicians invited to participate, 151 were randomized. Half of the fictional patients (41/90; 45% [95%CI 37-53%]) would be enrolled in the RCT even though the control-arm treatment of the RCT was not considered appropriate for them in the context of care. This rate differed by type of comparator (55% for non-head-to-head RCTs vs 6% for head-to-head RCTs; adjusted OR (aOR) 23.9 [95%CI 5.5-92.7]) and duration of trial control treatment (56% for ≤ 24 weeks and 15% for > 24 weeks; aOR 10.7 [95%CI 2.8-63.9]) but not patient RA activity (aOR 2.5 [95%CI 1.0-6.6]). Limitations: Fictional patients, RA only. Conclusions: Control treatments in RCTs of biologics in RA are often deemed not acceptable in the context of usual care, especially those for non-head-to-head RCTs. These findings raise ethical concerns and challenge the choice of the comparator in RCTs.
    Article · Sep 2015 · Journal of clinical epidemiology
  • [Show abstract] [Hide abstract] ABSTRACT: A germline and coding polymorphism (rs2230926) of TNFAIP3 (A20), a central gatekeeper of nuclear factor-kappa B (NF-kB) activation, was recently found associated with primary Sjögren's syndrome (pSS)-associated lymphoma in a French cohort. We aimed to replicate this association. The rs2230926 polymorphism was genotyped in cases and controls of European ancestry from two independent cohorts from UK and France. Case control association tests were performed (Fisher's test) in the two cohorts, followed by a meta-analysis of the two cohorts. The UK cohort included 308 controls and 590 patients with pSS including 31 with a history of lymphoma. The French cohort consisted of 448 controls and 589 patients with pSS including 47 with lymphoma. In both cohorts, the rs2230926 missense polymorphism was not associated with pSS. However, in the UK cohort, the rs2230926G variant was significantly associated with pSS-associated lymphoma (OR=2.74, 95% CI (1.07 to 7.03), p=0.0423, compared with patients with pSS without lymphoma, and OR=3.12, 95% CI (1.16 to 8.41), p=0.0314, compared with healthy controls) as observed in the French cohort. The meta-analysis of the two cohorts confirmed these results (OR=2.48, 95% CI (1.87 to 3.28) p=0.0037 and OR=2.60, 95% CI (1.91 to 3.53) p=0.0031, respectively). This study confirms the role of A20 impairment in pSS-associated lymphoma. Subtle germline abnormalities of genes leading to impaired control of NF-kB activation in B cells continuously stimulated by autoimmunity enhance the risk of lymphoma. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Article · Sep 2015 · Annals of the rheumatic diseases
  • Raphaele Seror · Xavier Mariette
    Article · Aug 2015 · Arthritis and Rheumatology

Publication Stats

2k Citations


  • 2015
    • Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 2014
    • Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud)
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      Lutetia Parisorum, Île-de-France, France