Papers by thierry schaeverbeke
Acta dermato-venereologica, 2017
The aim of this study was to identify the association between the severity or pattern of psoriasi... more The aim of this study was to identify the association between the severity or pattern of psoriasiform reactions and the underlying disease. A retrospective study was conducted between January 2012 and May 2015. Adult patients who developed psoriasiform eruptions whilst being treated with TNFα inhibitors were included. For each patient, 3 independent blinded dermatologists graded twice the severity of the lesions according to 6 clinical psoriasiform eruption types. Inter-and intra-individual kappa tests were performed to evaluate the robustness of the scoring system. The association between severity score levels or the pattern of reactions and the underlying disease was assessed. The severity scoring system showed good inter-and intra-observer reproducibility. Women patients treated with TNFα inhibitors for inflammatory bowel diseases showed a higher risk of developing severe reactions with scalp and skin-fold involvement.
Annals of the Rheumatic Diseases, May 19, 2021
7 (21.2) High disease activity 22 (47.8) Very high disease activity 5 (10.9) V1: EULAR response, ... more 7 (21.2) High disease activity 22 (47.8) Very high disease activity 5 (10.9) V1: EULAR response, n (%) n=23 V1: MDA, n (%) n=75 Good 7 (30.4) Yes 21 (28.0) BASDAI, mean (SD) n=50 Moderate 8 (34.8) V0 / V1 5.99 (2.1) / 4.92 (2.3)* No response 8 (34.8) V1: BASDAI50, n (%) 7 (14.0) ASAS-HI, mean (SD) n=48 V0 / V1 10.67 (3.8) / 9.68 (4.
Annals of the Rheumatic Diseases, Jun 5, 2015
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
RMD Open
ObjectiveThere is limited experience regarding the use of biological disease-modifying antirheuma... more ObjectiveThere is limited experience regarding the use of biological disease-modifying antirheumatic drug (bDMARD) and JAK inhibitor (JAKi) for the management of immune checkpoint inhibitors (ICI)-induced inflammatory arthritis. We aimed to assess their efficacy and safety in this setting.MethodsUsing the Club Rhumatismes and Inflammation French network, we conducted a multicentre, retrospective, observational study of patients with cancer diagnosed with inflammatory arthritis under ICI(s) and treated with bDMARD or JAKi. Clinical data were collected using a standardised case report form.ResultsTwenty patients (60% men, median age 69.5 years) were included, with rheumatoid arthritis (RA)-like (n=16), polymyalgia rheumatica-like (n=2) or psoriatic arthritis-like (n=2) clinical presentation. Two patients had pre-existing RA. 90% were treated with glucocorticoids as first-line therapy and 60% received methotrexate prior to bDMARD or JAKi. Anti-interleukin-6 receptor (IL-6R) therapy was...
Science Translational Medicine, 2021
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of to... more Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance toward self-nucleic acids, autoantibody production, interferon expression and signaling, and a defect in the regulatory T (Treg) cell compartment. In this work, we identified that platelets from patients with active SLE preferentially interacted with Treg cells via the P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1) axis. Selectin interaction with PSGL-1 blocked the regulatory and suppressive properties of Treg cells and particularly follicular Treg cells by triggering Syk phosphorylation and an increase in intracytosolic calcium. Mechanistically, P-selectin engagement on Treg cells induced a down-regulation of the transforming growth factor–β axis, altering the phenotype of Treg cells and limiting their immunosuppressive responses. In patients with SLE, we found an up-regulation of P- and E-selectin both on microparticles and in their soluble forms that correlated with dise...
European Respiratory Journal, 2020
Question addressed by the studyMethotrexate (MTX) is a key anchor drug for rheumatoid arthritis (... more Question addressed by the studyMethotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD.MethodsThrough a case–control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques.ResultsAnalysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24–0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19–0.79; p=0.009). The combined estimate using both the derivation and validat...
The Journal of Rheumatology, 2019
Objective.Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in r... more Objective.Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T.Methods.Patients with RA from 10 countries who were starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model).Results.A t...
The Journal of Rheumatology, 2019
Objective.The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an inter... more Objective.The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings.Methods.Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score.Results.A total of 571 patients were recruited and 439 (76.9%) completed 2-yea...
Revue du Rhumatisme, 2019
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Arthritis Research & Therapy, 2019
Objectives: Adult-onset Still's disease (AOSD) phenotype appears to be dichotomized in systemic o... more Objectives: Adult-onset Still's disease (AOSD) phenotype appears to be dichotomized in systemic or chronic articular forms. As biologicals and particularly interleukin (IL)-1 and IL-6 blockers play a more and more prominent role in the treatment, their place requires clarification. This study aimed to identify factors predictive of treatment response to anakinra or tocilizumab and investigate whether the choice of biotherapy and delays in the initiation of biotherapy influenced the likelihood of steroid discontinuation. Methods: A multicenter exploratory retrospective study included all patients diagnosed with AOSD and receiving biological treatments in three regional hospitals until 2018. Clinical and biological characteristics at diagnosis and treatment-related data were collected. The nonparametric Mann-Whitney test was used to perform univariate analysis for quantitative variables, and Fisher's exact test was used for qualitative variables. Results: Twenty-seven patients were included. All but one patient achieved remission with either anakinra or tocilizumab. Treatment responses depended on disease phenotype: the presence of arthritis and a chronic articular phenotype were associated with a substantial response to tocilizumab with p = 0.0009 (OR 36 [2.6-1703]) and p = 0. 017 ), respectively, whereas the systemic form and the absence of arthritis were associated with a substantial response to anakinra with p = 0.0009 (OR 36 [2.6-1703]) and p = 0.017 ]), respectively. Tocilizumab increased the likelihood of corticosteroid withdrawal (p = 0.029) regardless of delays in initiation or when it was initiated relative to other treatment in the overall therapeutic strategy. Conclusion: This study highlights the therapeutic implications of the phenotypic dichotomy of AOSD and should help us better codify AOSD treatment.
BMJ, 2019
Objective To compare the effectiveness and safety of three non-tumour necrosis factor (TNF) α inh... more Objective To compare the effectiveness and safety of three non-tumour necrosis factor (TNF) α inhibitors (rituximab, abatacept, and tocilizumab) in the treatment of rheumatoid arthritis. Design Population based prospective study. Setting 53 university and 54 non-university clinical centres in France. Participants 3162 adults (>18 years) with rheumatoid arthritis according to 1987 American College of Rheumatology criteria, enrolled in one of the three French Society of Rheumatology registries; who had no severe cardiovascular disease, active or severe infections, or severe immunodeficiency, with follow-up of at least 24 months. Intervention Initiation of intravenous rituximab, abatacept, or tocilizumab for rheumatoid arthritis. Main outcome measure The primary outcome was drug retention without failure at 24 months. Failure was defined as all cause death; discontinuation of rituximab, abatacept, or tocilizumab; initiation of a new biologic or a combination of conventional disease ...
Rheumatology and Therapy, 2018
The objective of the study was to compare compliance and acceptability of a new auto-injector (AI... more The objective of the study was to compare compliance and acceptability of a new auto-injector (AI) versus syringe for administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA). Methods: We conducted a randomized, openlabel, parallel group study comparing AI to prefilled syringe (PFS). Adult patients with RA (ACR/EULAR 2010) receiving MTX (orally or by injection) for at least 3 months were allocated to AI or PFS for 6 months and then were allocated to AI for 6 further months. Two co-primary endpoints were defined at M6: percentage of patients with compliance at least 80%; change in functional capacity assessed by Health Assessment Questionnaire (HAQ). Secondary endpoints included quality of life (RaQoL), RA activity (DAS28), and acceptability. Local safety at injection site was assessed at each visit. Results: Two-hundred and sixty-five patients were randomized. The main analysis was conducted on per protocol set (99 AI and 98 PFS). Compliance was 96.2% in AI and 98.9% in PFS. Good complier rates were 89.9% and 94.9%, thus a difference of -5.0% (-18.9%; 8.9%). HAQ remained stable in both groups. No difference was found on RaQoL, change in RA activity, and safety profile. Autonomy, acceptability, and patient satisfaction were better with AI, and patients having had the experience of both AI and PFS preferred AI (p \ 0.001). Conclusions: Although this study did not demonstrate non-inferiority of AI versus PFS, compliance was excellent in the two groups, and AI, which was preferred by patients, is a valuable alternative to PFS for administration of MTX. Trial Registration: ClinicalTrials.gov identifier, NCT02553018. Funding: Nordic Pharma SAS.
Scientific reports, Jan 3, 2018
Spondyloarthritis (SpA) pathophysiology remains largely unknown. While the association with genet... more Spondyloarthritis (SpA) pathophysiology remains largely unknown. While the association with genetic factors has been established for decades, the influence of gut microbiota is only an emerging direction of research. Despite the remarkable efficacy of anti-TNF-α treatments, non-responders are frequent and no predictive factors of patient outcome have been identified. Our objective was to investigate the modifications of intestinal microbiota composition in patients suffering from SpA three months after an anti-TNF-α treatment. We performed 16S rDNA sequencing of 38 stool samples from 19 spondyloarthritis patients before and three months after anti-TNF-α treatment onset. SpA activity was assessed at each time using ASDAS and BASDAI scores. Some modifications of the microbiota composition were observed after three months of anti-TNF-α treatment, but no specific taxon was modified, whatever the clinical response. We identified a particular taxonomic node before anti-TNF-α treatment tha...
Rheumatology, 2017
Objectives. Observational studies have already reported the risk of serious infections in RA trea... more Objectives. Observational studies have already reported the risk of serious infections in RA treated with tocilizumab, but in limited samples. The aim of this study was to investigate the predictive risk factors for serious infections in the largest European registry of patients treated with tocilizumab for RA. Methods. A total of 1491 RA patients included in the French REGistryRoAcTEmra were analysed to calculate the incidence rate of first serious infections rate after initiation of tocilizumab. To identify independent factors associated with serious infections, a Cox model was performed. Results. Among the 1491 patients, average age 56.6 (13.6) years, 125 serious infections occurred in 122 patients (incidence rate of serious infection: 4.7/100 patient-years). Univariate analysis identified initial ACPA positivity as the only factor associated with a lower risk of serious infection [hazard ratio (HR) = 0.56, 95% CI: 0.36, 0.88]. Other factors significantly associated with a higher risk of serious infections were DAS28, concomitant Leflunomide (LEF) treatment, and absolute neutrophil count (ANC) at baseline. Initial ANC above 5.0 Â 10 9 /l (HR = 1.94, 95% CI: 1.32, 2.85; P < 0.001), negative ACPA (HR = 1.79, 95% CI: 1.15, 2.78; P = 0.012) at baseline and concomitant LEF treatment (LEF alone vs no treatment, HR = 2.18, 95% CI: 1.22, 3.88; P = 0.009) remained significantly associated with first serious infections in multivariate analysis after imputation for missing data. The rate of first serious infections in current practice is similar to that reported in clinical trials. High ANC (above 5.0 Â 10 9 at baseline), negative ACPA and concomitant therapy with LEF are predictive factors of serious infection, requiring in this case a tighter surveillance.
Rheumatology (Oxford, England), Apr 3, 2017
To investigate the frequency and risk factors of postoperative complications in RA patients treat... more To investigate the frequency and risk factors of postoperative complications in RA patients treated with abatacept (ABA). The Orencia RA registry recruited 1012 patients receiving ABA for RA in routine care. Data from patients treated with ABA who underwent surgery were reviewed to describe the frequency of postoperative complications. Characteristics of patients and surgeries with and without complications were compared to identify factors associated with complications. We identified 205 (20.3%) patients who underwent 263 surgeries, including 176 (66.9%) orthopaedic surgeries. Nineteen (7.2%) surgeries, in 19 patients (9.3%), entailed complications, including 7 delayed wound healing (2.7% of surgeries) and 6 surgical site infections (2.3% of surgeries). The median time between the last infusion of ABA and surgery was 5.9 weeks (range: 0.3-12.0 weeks), with no significant difference between patients with and without complications. The median corticosteroids daily dosage was higher i...
Scientific reports, Jan 20, 2016
Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic condition over the wo... more 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 ...
Joint Bone Spine, 2014
Objectives: To compare retention rates of adalimumab, etanercept and infliximab as first-line bio... more Objectives: To compare retention rates of adalimumab, etanercept and infliximab as first-line biotherapy in rheumatoid arthritis (RA), to determine causes of discontinuation, retention-associated factors, and retention rates of possible second-line TNF-␣ inhibitors (TNFi). Methods: In this retrolective, multicentric study, medical charts of RA patients starting TNFi between March 2005 and April 2009 were reviewed, with follow-up between two and six years. The retention rate was estimated using the Kaplan-Meier method. Comparison between TNFi was done after adjustment using a Cox model. Factors associated with better retention were identified by multivariate analysis. Results: Of the 706 patients included, the percentage continuing treatment after two years was 54.9, 61.9 and 48.7%, and the median retention was 31, 45 and 23 months for adalimumab, etanercept and infliximab, respectively. The hazard ratios (HRs) for discontinuation were greater with adalimumab and infliximab than etanercept (1.315, 95% CI [1.050-1.648] and 1.380, 95% CI [1.041-1.828], respectively). The HR for discontinuation due to inefficacy was significantly higher with adalimumab than etanercept. Adverse events were significantly higher with infliximab than etanercept. Past use of more DMARDs and higher baseline ESR were associated with better retention. The median retention of the secondline TNFi was 11, 43 and 19.1 months for adalimumab, etanercept, and infliximab, respectively. HRs for adalimumab discontinuation due to all causes were significantly greater than for etanercept. Conclusions: Etanercept had a better retention rate than adalimumab and infliximab as first-line biotherapy in RA, and than adalimumab as second-line biotherapy.
Revue du Rhumatisme, 2006
Objectifs. -Établir au nom de la Société française de rhumatologie des recommandations pour l'uti... more Objectifs. -Établir au nom de la Société française de rhumatologie des recommandations pour l'utilisation en pratique quotidienne des anti-TNFα au cours de la polyarthrite rhumatoïde (PR). Méthode. -La méthodologie recommandée par l'Anaes, la Collaboration AGREE et l'EULAR a été utilisée pour établir ces recommandations, structurées en trois thèmes : indication des anti-TNFα, initiation en pratique, surveillance et adaptation thérapeutique. Résultats. -Pour retenir l'indication d'un traitement anti-TNFα chez une personne souffrant de PR : 1) le diagnostic de PR doit être certain ; 2) la PR doit être active depuis plus d'un moisavec des éléments objectifs d'inflammationou évolutive sur le plan structural ; 3) un échec préalable au méthotrexate à dose optimale toléréeou à un autre traitement de fond en cas de contre-indicationest nécessaire ; 4) les contreindications doivent avoir été recherchées. Lors de l'initiation d'un anti-TNFα : 1) un bilan préthérapeutique et complet doit être réalisé ; 2) les trois anti-TNFα peuvent être employés, leur efficacité étant superposable ; 3) l'association au méthotrexate est recommandée quel que soit l'anti-TNFα ; 4) le suivi des patients doit être régulier et standardisé. L'adaptation se fonde sur les règles suivantes : 1) l'objectif thérapeutique est la réponse EULAR ; 2) en cas de non réponse, il est possible de modifier la posologie ou la fréquence des injections, ou de remplacer un anti-TNFα par un autre ; 3) en cas d'intolérance à l'un des anti-TNFα, l'utilisation d'un autre anti-TNFα est possible selon la nature de l'effet indésirable Revue du Rhumatisme 73 (2006) 726-735
Rheumatology, 2009
Objectives. In early and active RA despite MTX, continuous treatment with TNF blockers in combina... more Objectives. In early and active RA despite MTX, continuous treatment with TNF blockers in combination with MTX is recommended. To compare this strategy with an initial combination of MTX and adalimumab (ADA) given for 3 months and then adjusted based on the disease activity status. Methods. Prospective unblinded randomized multicentre controlled 1-year trial in which 65 patients with early (<6 months) and active [disease activity score (DAS28 ESR ) >5.1] RA were assigned to Group 1 (32 patients): MTX (0.3 mg/kg/week, maximum of 20 mg/week, without escalating dose regimen) or to Group 2 (33 patients): initial combination therapy with MTX (as in Group 1) and ADA (40 mg eow). In both groups, treatment was adjusted every 3 months. The aim was to achieve a low DAS (DAS28 ESR <3.2). Results. From Week 12 until Week 52, seven patients in Group 1 and 11 patients in Group 2 remained in low disease activity state while receiving MTX monotherapy (P ¼ 0.28). The 1-year area under the curve (AUC) of DAS28 was lower in Group 2 owing to an initial better response. The total intake of anti-TNF-and the mean increase in total modified Sharp score was similar in the two groups. Conclusions. Initial combination of MTX and ADA and then an adjusted based on the disease activity status achieved a faster control of disease activity but did not increase the number of patients for whom anti-TNF-treatment was not needed after 12 weeks nor a better subsequent clinical or radiological outcome than a 3-month delayed initiation of anti-TNF in patients with still active disease despite MTX.
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Papers by thierry schaeverbeke