Patrick Durez

Review Epidemiological Review of Injuries in Rugby Union

Rugby is a sport that is growing in popularity. A contact sport par excellence, it causes a signi... more Rugby is a sport that is growing in popularity. A contact sport par excellence, it causes a significant number of injuries. In Rugby Union, there are 30 to 91 injuries per 1000 match hours. This epidemiological review of injuries incurred by rugby players mentions the position and type of injuries, the causes, time during the match and season in which they occur and the players' positions as well as the length of players' absences following the injury.

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Should We Use bDMARDs as an Induction Therapy in Early and Severe Rheumatoid Arthritis? Results at 5 years from the ERA UCLouvain Brussels Cohort

Rheumatology and Therapy

Introduction: This study sought to analyze the benefit of an early induction therapy with a biolo... more Introduction: This study sought to analyze the benefit of an early induction therapy with a biological disease-modifying anti-rheumatic drugs (bDMARD) during the first year of treatment with a 5-year follow-up in early rheumatoid arthritis (ERA). Methods: We included ERA patients from the UCLouvain Brussels cohort who met the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 classification criteria and were naïve to DMARDs. ERA patients were divided into two groups according to whether they received an induction bDMARD therapy or a standard therapy with methotrexate (MTX). Clinical response after the induction treatment at 6 and 12 months followed by a MTX maintenance therapy at 36 and 60 months was evaluated. Results: Data from 470 ERA patients were collected, 189 received a bDMARD and 281 initiated MTX alone. In the bDMARD group, disease activity and HAQ were higher at baseline. A total of 391 patients were followed up to 5 years. We then divided each group into two subgroups according to the last treatment they received at 5 years: bDMARD [ MTX (n = 95), bDMARD [ bDMARD (n = 59); MTX [ MTX (n = 134), MTX [ bDMARD (n = 103). During the induction, we observed a clinical response with a large number of patients achieving DAS28-CRP remission. According to a treat-totarget (T2T) approach, remission rate was stable on MTX monotherapy or rescued by the addition or prolongation of a bDMARD. Interestingly, bDMARD followed by a MTX maintenance therapy experienced a stable and sustained DAS28-CRP remission rate in 53% of the ERA patients at year 5. Conclusions: Long-term remission is an achievable goal in ERA. Our results suggest that a bDMARD induction therapy followed by MTX maintenance therapy could be an interesting option.

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THU0149 The 54-Week Results of Interferon-γ Release Assay in A Phase III Study Comparing SB2, An Infliximab Biosimilar, To Infliximab Reference Product in Patients with Rheumatoid Arthritis: Table 1

Annals of the Rheumatic Diseases, 2016

Background Patients who are being treated with anti-TNF therapy are at increased risk of developi... more Background Patients who are being treated with anti-TNF therapy are at increased risk of developing active tuberculosis (TB) by reactivation of latent TB infection (LTBI) or de novo infection. SB2 is developed as a biosimilar of the infliximab reference product (INF). The primary results (30-week) and 54-week results of Phase III study have been reported1,2. Objectives To evaluate the prevalence of positive interferon-γ release assay (IGRA) at Screening, the incidence of positive seroconversion in IGRA, and the incidence of active TB in the patients receiving SB2 or INF for 54 weeks. Methods This study is a randomised, double-blind phase III study. IGRA (QuantiFERON® Gold in-tube test) was performed at Screening, Week 22 and Week 54. Patients who have been diagnosed as active TB were excluded from the study. Patients with a positive IGRA test without any evidence of active TB could be enrolled after receiving TB prophylaxis treatment. Patients who newly seroconverted during the study also were recommended to receive TB prophylaxis. Results Of 804 patients with IGRA results at Screening, 143 patients (17.8% of 804) had positive results. Among them, 46 patients (19 patients in SB2 and 27 patients in INF) were randomised after the 30-days of TB prophylaxis treatment and the others were excluded from the study. At Week 22 and 54 or early termination visit, respectively, 19 (6.6%) and 7 (2.4%) patients in SB2 and 20 (6.8%) and 7 (2.4%) patients in INF had newly positive IGRA results. Among the patients with positive IGRA results at Week 22, 73.7% (14/19) in SB2 and 50.0% (10/20) in INF were treated with anti-TB treatment. During the study period, there was 1 active TB case in each treatment group (tuberculous pleurisy in SB2 [Korea] and pulmonary tuberculosis in INF [Lithuania]) and there was no case of active TB reported in patients with positive IGRA results at Screening or Week 22.Table 1. Positive interferon-γ release assaya rate during the study IGRA test time SB2 (N=290) INF (N=293) Positive IGRA Seroconversionb Positive IGRA Seroconversionb n (%) n (%) n (%) n (%) Screeningc 19 (6.6%) 27 (9.2%) Week 22 28 (9.7%) 19 (6.6%) 36 (12.3%) 20 (6.8%) Week 54 or early termination 26 (9.0%) 7 (2.4%) 24 (8.2%) 7 (2.4%) aPatients, whose first and second interferon-γ release assay results were indeterminate, were considered to have the positive IGRA (at Screening 1 patient in each SB2 and INF; at Week 22, 4 patients in SB2 and 5 patients in INF for both positive IGRA and seronconversion; at Week 54, no patient in each SB2 and INF). bSeroconversion defined as negative to positive test change at each test time. cRandomised patients only. Conclusions The incidence of positive seroconversion in IGRA was comparable between the two treatment groups. Among patients with positive IGRA results at Screening or Week 22, there were no cases of active TB and only 2 cases of active TB were reported in this study. IGRA is therefore an useful method to prevent active TB in anti-TNF treated RA patients. References Choe JY et al. Ann Rheum Dis. 2015–207764 [Epub ahead of print] Choe JY et al. Arthritis Rheumatol. 2015; 67 (suppl 10), 2056 Disclosure of Interest P. Durez Consultant for: Samsung Bioepis, Speakers bureau: BMS, MSD, Lilly, UCB, Pfizer, E. Mysler: None declared, J. S. Smolen Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glazo, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB, J.-Y. Choe Grant/research support from: Samsung Bioepis, Consultant for: Samsung Bioepis, J. Choi Employee of: Samsung Bioepis, Y. H. Rho Employee of: Samsung Bioepis

A Cross-Sectional and Longitudinal Study to Define Alarmins and A-SAA Variants as Companion Markers in Early Rheumatoid Arthritis

Frontiers in Immunology, 2021

Nowadays, in the study of rheumatoid arthritis (RA), more and more interest is directed towards a... more Nowadays, in the study of rheumatoid arthritis (RA), more and more interest is directed towards an earlier effective therapeutic intervention and the determination of companion markers for predicting response to therapy with the goal to prevent progressive joint damage, deformities, and functional disability. With the present work, we aimed at quantifying in a cohort of early RA (ERA) patients naïve to DMARD therapy, proteins whose increase was previously found associated with RA: serum amyloid A (A-SAA) and alarmins. Five A-SAA variants (SAA1α, SAA1β, SAA1γ, SAA2α, and SAA2β) but also S100A8 and S100A9 proteins were simultaneously quantified in plasma applying a method based on single targeted bottom-up proteomics LC-MS/MS. First, we compared their expression between ERA (n = 100) and healthy subjects (n = 100), then we focused on their trend by monitoring ERA patients naïve to DMARD treatment, 1 year after starting therapy. Only SAA1α and SAA2α levels were increased in ERA patient...

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Subcutaneous injection of CNTO 148 compared with placebo in patients with active rheumatoid arthritis despite treatment with methotrexate: A randomized, double-blind, dose-ranging trial

Arthritis & Rheumatism, 2005

Final 5-Year Safety and Efficacy Results Of a Phase 3, Randomized, Placebo-Controlled Trial Of Golimumab In Methotrexate-naive Patients With Rheumatoid Arthritis

Arthritis & Rheumatism, 2013

Common Transcriptomic Effects of Abatacept and Other DMARDs on Rheumatoid Arthritis Synovial Tissue

Frontiers in Immunology, 2021

ObjectivesOur goal was to assess for the histological and transcriptomic effects of abatacept on ... more ObjectivesOur goal was to assess for the histological and transcriptomic effects of abatacept on RA synovia, and to compare them with previously published data from four other DMARDs: tocilizumab, rituximab, methotrexate, and adalimumab.MethodsSynovial tissue was obtained using ultrasound-guided biopsy from affected joints of 14 patients, before and 16 weeks after treatment with subcutaneous abatacept 125 mg weekly. Paraffin-sections were stained and scored for CD3+, CD20+, and CD68+ cell infiltration. Transcriptional profiling was performed using GeneChip Human Genome U133 Plus 2.0 arrays (Affymetrix) and analyzed on Genespring GX (Agilent). Pathway analyses were performed on Genespring GX, Metascape, and EnrichR.ResultsGene expression analysis identified 304 transcripts modulated by abatacept in synovial tissue. Downregulated genes were significantly enriched for immune processes, strongly overlapping with our findings on other therapies. Data were pooled across these studies, rev...

format_quoteAbatacept primarily modulates lymphocyte-related transcripts, enhancing knowledge of T-cell interactions in RA synovia post-treatment.format_quote

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Preliminary Results of first Belgian Cohort of Juvenile Idiopathic Arthritis: Where Do we Stand in Terms of Quality of Care and Remission?

BackgroundJuvenile idiopathic arthritis (JIA) represents a very heterogeneous disease, and our ob... more BackgroundJuvenile idiopathic arthritis (JIA) represents a very heterogeneous disease, and our objectives were to describe the first Belgian cohort of children with JIA, assess their disease characteristics and outcome and identify potential markers of prognosis.MethodsThe CAP48 cohort is a multicentric observational study of children with a recent or well-established diagnosis of JIA (naïve or not to treatment at baseline), evaluated every 6 months during a follow-up of 5 to 10 years.ResultsThere were 125 children included in the cohort, composed of 25 naïve and 100 established patients. The patients had a median age of 6.2 and 4.2 years at onset in the naïve and established cohort respectively, with a predominance of female. All subtypes of JIA were represented in both cohorts. The mean DAS28-CRP and JADAS10-CRP at baseline in naïve patients was 2.52 and 6.0 respectively. Uveitis occurred in 19% of patients and was strongly associated with presence of antinuclear antibodies (odds ...

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Réponse clinique précoce et progression radiographique à long terme dans la polyarthrite rhumatoïde débutante : la rémission clinique à 6 mois reste l’objectif à atteindre

Revue du Rhumatisme, 2019

Objectifs.-Évaluer la corrélation entre progression structurale en radiographie à 5 ans et rémiss... more Objectifs.-Évaluer la corrélation entre progression structurale en radiographie à 5 ans et rémission clinique précoce dans la PR débutante. Secondairement, évaluer la corrélation entre l'apparition d'érosion sur une articulation initialement saine et la rémission clinique précoce. Méthodes.-Étude rétrospective monocentrique de 133 patients présentant une PR débutante selon les critères ACR. Deux radiologues ont quantifié indépendamment l'atteinte radiologique structurale des mains et des avant-pieds par le score de Sharp Van der Heijde (SVdH) au diagnostic et à 5 ans. Deux groupes de patients ont été constitués : « RX-STAB » avec une évolution du SVdH ≤ 10 et « RX-PROG » avec une évolution du SVdH > 10. La réponse clinique a été évaluée à 3, 6 et 12 mois avec une rémission clinique définie par les scores DAS28-CRP, SDAI, CDAI et selon l'analyse booléenne des critères EULAR ACR. Résultats.-Un total de 90 patients appartenaient au groupe RX-STAB (évolution moyenne du score SVdH de 2,4 ± 2,9) et 43 au groupe RX-PROG (22,9 ± 13,4). Les scores d'activité clinique à 6 mois étaient plus élevés dans le groupe RX-PROG (p < 0,05). La sensibilité de l'obtention de la rémission clinique à 6 mois selon les scores DAS28-CRP, SDAI, CDAI et le critère booléen pour la prédiction d'une bonne évolution radiographique à 5 ans étaient respectivement de 58,6 %, 39,1 %, 40,0 % et 32,2 % ; leur spécificité était de 73,8 %, 85,7 %, 83,7 % et 90,5 %. Conclusion.-Obtenir une rémission clinique à 6 mois est essentiel pour prévenir la progression structurale dans la PR débutante.

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Efficacy and safety of subcutaneous infliximab versus adalimumab, etanercept and intravenous infliximab in patients with rheumatoid arthritis: a systematic literature review and meta-analysis

Expert Review of Clinical Immunology, 2020

Objectives: There are few comparative data for tumor necrosis factor inhibitors in patients with ... more Objectives: There are few comparative data for tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA). Methods: Historical data for reference product/biosimilar intravenous infliximab, or adalimumab and etanercept, were pooled and compared with phase 3 study results for a subcutaneous (SC) formulation of the infliximab biosimilar CT-P13, in a systematic review and meta-analysis (PROSPERO: CRD42019149621). Results: The authors identified 13 eligible controlled trials that randomized over 5400 participants to prespecified treatments of interest. Comparison with pooled historical data suggested a numerical advantage for CT-P13 SC over intravenous infliximab for almost every prespecified efficacy outcome evaluated, including Disease Activity Score in 28 joints (C-reactive protein/erythrocyte sedimentation rate), Clinical/ Simplified Disease Activity Index scores, American College of Rheumatology responses, and multiple measures of disease remission and low disease activity; for the majority of outcomes, there was no overlap in 95% confidence intervals between groups. A numerical advantage for CT-P13 SC was also observed for safety outcomes (adverse events, infections, and discontinuations). Similar, but less marked, trends were observed for comparison with historical efficacy and safety data for adalimumab/etanercept. Conclusion: CT-P13 SC offers an improved or similar benefit-to-harm ratio compared with infliximab (intravenous) and adalimumab/etanercept, for the treatment of moderate-to-severe RA.

format_quoteMeta-analysis revealed a numerical advantage for CT-P13 SC over infliximab IV for achieving DAS28-ESR remission at 30 weeks.format_quote

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Anti-TNF Induced Sarcoidosis-Like Disease in Rheumatoid Arthritis Patients: Review Cases from the RA UCLouvain Brussels Cohort

Rheumatology and Therapy

Introduction: Drug-induced sarcoidosis-like disease is a rare side effect of anti-tumor necrosis ... more Introduction: Drug-induced sarcoidosis-like disease is a rare side effect of anti-tumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA) patients. The most commonly involved organs in such condition are the lungs, skin, and lymph nodes. The aim of this study is to report the number of cases and the clinical manifestations of sarcoidosis induced by anti-TNF in our RA UCLouvain Brussels cohort. Methods: All case records of RA patients ever treated with a TNF inhibitor and presenting anti-TNF induced sarcoidosis in our rheumatology centers from 2000 to 2021 were retrospectively reviewed. Results: Our RA UCLouvain Brussels cohort includes 2492 patients. Among them, 697 patients have been or are exposed to a TNF inhibitor. Only four patients with sarcoidosis induced by anti-TNF were identified and reviewed. Patient 1 was classified as incomplete Heerfordt syndrome. Patient 2 was a case of sarcoid-like granulomatosis manifesting as lifethreatening hypercalcemia, acute kidney injury and atypical parenchymal pneumopathy. Patients 3 and 4 developed pulmonary sarcoidosis with hilar adenopathies. The TNF inhibitor was etanercept for the first three patients and infliximab for the last one. The time occurrence of sarcoidosis was highly variable after anti-TNF exposure. All patients recovered after glucocorticoid treatment and the discontinuation of the anti-TNF agent. Conclusions: This case highlights this rare paradoxical side effect and the variability of the clinical presentation. Further studies should analyze the immunopathology of such conditions.

format_quoteAll patients recovered after glucocorticoid treatment and stopping anti-TNF agents, underscoring treatment effectiveness.format_quote

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Identification of poor prognostic joint locations in an early rheumatoid arthritis cohort at risk of rapidly progressing disease: a post-hoc analysis of the Phase III AGREE study

BMC Rheumatology

Background Rheumatoid arthritis (RA) is a heterogeneous disease with established poor prognostic ... more Background Rheumatoid arthritis (RA) is a heterogeneous disease with established poor prognostic factors such as seropositivity, joint damage, and high disease activity at an early, treatment-naïve stage of disease. However, few studies have examined if specific joint locations are correlated with these factors in such a population. This analysis explored the potential correlation of individual swollen and erosive joints with other disease characteristics at baseline and with remission rates in a post-hoc analysis of the Phase III randomized AGREE study. Methods Methotrexate (MTX)-naïve, erosive, RF- and/or ACPA-positive early RA patients (N = 509) were retrospectively evaluated. Baseline joint swelling was analyzed for large and small joints. Baseline erosions were analyzed for wrist, MCP1–5, IP1, PIP2–5 and MTP1–5. Remission rates were assessed after 6 months of treatment with abatacept (ABA) + MTX (N = 256) or MTX (N = 253). The following statistical tests were used: Chi-Square o...

format_quotePatients receiving ABA + MTX showed higher remission rates compared to MTX alone (13.7% vs 5.5%; p < 0.01), especially with baseline swollen wrist (14.0% vs 4.4%; p < 0.001).format_quote

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41:7; Personal non-commercial use only

ABSTRACT. Objective. Our study describes the 10-year followup data of the Belgian Expanded Access... more ABSTRACT. Objective. Our study describes the 10-year followup data of the Belgian Expanded Access Program (EAP) for infliximab (IFX), which included patients with active rheumatoid arthritis who were refractory to methotrexate. The objectives of the study were to evaluate the continuation rate, reasons for discontinuation, and longterm disease control under IFX treatment, and to study baseline characteristics associated with longterm successful IFX therapy. Methods. Between February 2000 and September 2001 , 511 patients were enrolled in the Belgian IFX EAP, and 507 effectively started IFX therapy. Previously reported data showed that 160 patients were still treated with IFX after 7 years of followup. We describe the therapy status, reasons for IFX discontinuation, and the level of disease activity of this subgroup after 10 years of followup. Baseline characteristics of the total EAP cohort were used to describe variables associated with longterm successful IFX treatment. Results. A...

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Voevodsky Letter to

Response to the commentary ‘Pooled indices to measure rheumatoid arthritis activity: a good refle... more

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Three-year follow-up of rituximab in rheumatoid arthritis: results from the Belgian MIRA (MabThera in Rheumatoid Arthritis) registry

Arthritis & Rheumatism, 2012

Anti-TNF Induced Sarcoidosis-Like Disease in Rheumatoid Arthritis Patients: Review Cases from the RA UCLouvain Brussels Cohort

Rheumatology and Therapy

Introduction: Drug-induced sarcoidosis-like disease is a rare side effect of anti-tumor necrosis ... more Introduction: Drug-induced sarcoidosis-like disease is a rare side effect of anti-tumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA) patients. The most commonly involved organs in such condition are the lungs, skin, and lymph nodes. The aim of this study is to report the number of cases and the clinical manifestations of sarcoidosis induced by anti-TNF in our RA UCLouvain Brussels cohort. Methods: All case records of RA patients ever treated with a TNF inhibitor and presenting anti-TNF induced sarcoidosis in our rheumatology centers from 2000 to 2021 were retrospectively reviewed. Results: Our RA UCLouvain Brussels cohort includes 2492 patients. Among them, 697 patients have been or are exposed to a TNF inhibitor. Only four patients with sarcoidosis induced by anti-TNF were identified and reviewed. Patient 1 was classified as incomplete Heerfordt syndrome. Patient 2 was a case of sarcoid-like granulomatosis manifesting as lifethreatening hypercalcemia, acute kidney injury and atypical parenchymal pneumopathy. Patients 3 and 4 developed pulmonary sarcoidosis with hilar adenopathies. The TNF inhibitor was etanercept for the first three patients and infliximab for the last one. The time occurrence of sarcoidosis was highly variable after anti-TNF exposure. All patients recovered after glucocorticoid treatment and the discontinuation of the anti-TNF agent. Conclusions: This case highlights this rare paradoxical side effect and the variability of the clinical presentation. Further studies should analyze the immunopathology of such conditions.

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Distinct effects of infliximab and intravenous pulse methylprednisolone on CRP, interleukin-6 and matrix metalloproteinase-3 serum titers in rheumatoid arthritis patients with active disease despite methotrexate. A prospective randomised comparative study

Oral glucocorticoids have no impact on the efficacy or safety profile of rituximab in rheumatoid arthritis patients with inadequate response to TNF inhibitors (REFLEX study)

Annals of the Rheumatic Diseases, 2006

Identification of poor prognostic joint locations in an early rheumatoid arthritis cohort at risk of rapidly progressing disease: a post-hoc analysis of the Phase III AGREE study

BMC Rheumatology

Background Rheumatoid arthritis (RA) is a heterogeneous disease with established poor prognostic ... more Background Rheumatoid arthritis (RA) is a heterogeneous disease with established poor prognostic factors such as seropositivity, joint damage, and high disease activity at an early, treatment-naïve stage of disease. However, few studies have examined if specific joint locations are correlated with these factors in such a population. This analysis explored the potential correlation of individual swollen and erosive joints with other disease characteristics at baseline and with remission rates in a post-hoc analysis of the Phase III randomized AGREE study. Methods Methotrexate (MTX)-naïve, erosive, RF- and/or ACPA-positive early RA patients (N = 509) were retrospectively evaluated. Baseline joint swelling was analyzed for large and small joints. Baseline erosions were analyzed for wrist, MCP1–5, IP1, PIP2–5 and MTP1–5. Remission rates were assessed after 6 months of treatment with abatacept (ABA) + MTX (N = 256) or MTX (N = 253). The following statistical tests were used: Chi-Square o...

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41:7; Personal non-commercial use only

ABSTRACT. Objective. Our study describes the 10-year followup data of the Belgian Expanded Access... more ABSTRACT. Objective. Our study describes the 10-year followup data of the Belgian Expanded Access Program (EAP) for infliximab (IFX), which included patients with active rheumatoid arthritis who were refractory to methotrexate. The objectives of the study were to evaluate the continuation rate, reasons for discontinuation, and longterm disease control under IFX treatment, and to study baseline characteristics associated with longterm successful IFX therapy. Methods. Between February 2000 and September 2001 , 511 patients were enrolled in the Belgian IFX EAP, and 507 effectively started IFX therapy. Previously reported data showed that 160 patients were still treated with IFX after 7 years of followup. We describe the therapy status, reasons for IFX discontinuation, and the level of disease activity of this subgroup after 10 years of followup. Baseline characteristics of the total EAP cohort were used to describe variables associated with longterm successful IFX treatment. Results. A...

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