41 results on '"Farah, Tamirou"'
Search Results
2. O40 Impact of glucocorticoid dose on complete response, serious infections, and mortality during the initial therapy of lupus nephritis: a systematic review and meta-analysis of the standard of care arms of randomized controlled trials
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Farah Tamirou, Frederic Houssiau, Ali Duarte-García, Maria Dall’Era, Brad H Rovin, Larry J Prokop, Gabriel Figueroa-Parra, Cynthia S Crowson, Michael S Putman, Fernando C Fervenza, Alain Sanchez-Rodriguez, María C Cuéllar-Gutiérrez, Mariana González-Treviño, Jaime Flores-Gouyonnet, José A Meade-Aguilar, and M Hassan Murad
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2024
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3. Long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases: The ERN-ReCONNET VACCINATE study
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Chiara Tani, Chiara Cardelli, Roberto Depascale, Anna Gamba, Luca Iaccarino, Andrea Doria, Matilde Bandeira, Sara Paiva Dinis, Vasco C. Romão, Emanuele Gotelli, Sabrina Paolino, Maurizio Cutolo, Niccolò Di Giosaffatte, Alessandro Ferraris, Paola Grammatico, Lorenzo Cavagna, Veronica Codullo, Carlomaurizio Montecucco, Valentina Longo, Lorenzo Beretta, Ilaria Cavazzana, Micaela Fredi, Silvia Peretti, Serena Guiducci, Marco Matucci-Cerinic, Stefano Bombardieri, Gerd R. Burmester, João E. Fonseca, Charissa Frank, Ilaria Galetti, Eric Hachulla, Ulf Müller-Ladner, Matthias Schneider, Vanessa Smith, Farah Tamirou, Jacob M. Van Laar, Ana Vieira, Rossella D'Urzo, Sara Cannizzo, Andrea Gaglioti, Diana Marinello, Rosaria Talarico, and Marta Mosca
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ystemic autoimmune disease ,SARS-CoV-2 ,COVID-19 ,Vaccination ,Flare ,Breakthrough infection ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: Vaccination is one of the most important measures to contain the COVID-19 pandemic, especially for frail patients. VACCINATE is a multicentre prospective observational study promoted by the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) aimed at assessing the long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases (rcCTDs) in terms of efficacy and safety. Methods: Adult rcCTDs patients were eligible for recruitment. Demographic, clinical and vaccination data were collected at enrolment. Follow-up visits were scheduled 4, 12, 24, 36 and 48 weeks after completion of the first vaccination cycle; data on adverse events, disease exacerbations and the occurrence of new SARS-CoV-2 infections were collected at these time-points. Findings: 365 rcCTDs patients (87 % female, mean age 51.8 ± 14.6 years) were recruited. Overall, 200 patients (54.8 %) experienced at least one adverse event, generally mild and in most cases occurring early after the vaccination. During follow-up, 55 disease exacerbations were recorded in 39 patients (10.7 %), distributed over the entire observation period, although most frequently within 4 weeks after completion of the vaccination cycle. The incidence of new SARS-CoV-2 infections was 8.9 per 1000 person-months, with no cases within 12 weeks from vaccine administration and an increasing trend of infections moving away from the primary vaccination cycle. Only one case of severe COVID-19 was reported during the study period. Interpretation: COVID-19 vaccination seems effective and safe in rcCTDs patients. The rate of new infections was rather low and serious infections were uncommon in our cohort. No increased risk of disease flares was observed compared to previous disease history; however, such exacerbations may be potentially severe, emphasising the need for close monitoring of our patients.
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- 2023
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4. Real-life prevalence of progressive fibrosing interstitial lung diseases
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Maureen Gagliardi, Damienne Vande Berg, Charles-Edouard Heylen, Sandra Koenig, Delphine Hoton, Farah Tamirou, Thierry Pieters, Benoit Ghaye, and Antoine Froidure
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Medicine ,Science - Abstract
Abstract The concept of progressive fibrosing interstitial lung disease (PF-ILD) has recently emerged. However, real-life proportion of PF-ILDs outside IPF is still hard to evaluate. Therefore, we sought to estimate the proportion of PF-ILD in our ILD cohort. We also determined the proportion of ILD subtypes within PF-ILD and investigated factors associated with PF-ILDs. Finally, we quantified interobserver agreement between radiologists for the assessment of fibrosis. We reviewed the files of ILD patients discussed in multidisciplinary discussion between January 1st 2017 and December 31st 2019. Clinical data, pulmonary function tests (PFTs) and high-resolution computed tomography (HRCTs) were centrally reviewed. Fibrosis was defined as the presence of traction bronchiectasis, reticulations with/out honeycombing. Progression was defined as a relative forced vital capacity (FVC) decline of ≥ 10% in ≤ 24 months or 5%
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- 2021
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5. 605 The Systemic Lupus Erythematosus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and Lupus Foundation of America (LFA) Damage Index Revision – Item Generation Phase
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Farah Tamirou, Nathalie Costedoat-Chalumeau, Ian N Bruce, Guillermo Ruiz-Irastorza, Hermine I Brunner, Ellen M Ginzler, John G Hanly, Murat Inanc, Évelyne Vinet, Sindhu R Johnson, Ann E Clarke, Clóvis A Silva, Anselm Mak, Megan RW Barber, Jiacai Cho, Burak Kundakci, Abida Hasan, Naureen Kabani, Kaitlin Lima, Livia Lindoso, Rosalind Ramsey- Goldman, and Vitor C Trindade
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2022
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6. Worse long-term renal outcome of lupus nephritis patients of African descent living in Europe
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Farah Tamirou, Frederic Houssiau, Nathalie Costedoat-Chalumeau, Antoine Enfrein, Adexandre Karras, Veronique Le Guern, and Valérie Pirson
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Medicine - Abstract
Introduction Prognosis of lupus nephritis (LN) among patients of African descent living in Europe has been understudied.Methods In a retrospective study performed in two European university hospitals, we compared the prognosis of LN in patients of African descent or Caucasians. Remission was defined as a urine protein to creatinine (uP/C) ratio1 g/g, leading to a repeat kidney biopsy and/or immunosuppressive treatment change. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate≤60 mL/min/1.73 m2. Adherence was retrospectively assessed through medical files and/or hydroxychloroquine level measurements.Results 52 patients of African descent and 85 Caucasian patients were included in this analysis. Class III and isolated class V LN were more common among patients of African descent. Time to first renal remission did not differ between ethnic subgroups. By contrast, patients of African descent suffered from earlier renal flares, CKD was more common and time to CKD was shorter after a flare. In a multivariate analysis, African ancestry was an independent risk factor for progression to CKD. We observed no significant difference in non-adherence to treatment between the two groups.Conclusion LN patients of African descent have worse renal outcomes, mainly explained by a higher rate of renal flare.
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- 2022
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7. High p16INK4a, a marker of cellular senescence, is associated with renal injury, impairment and outcome in lupus nephritis
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Farah Tamirou, Frederic Houssiau, Selda Aydin, Bernard Lauwerys, Gaëlle Tilman, Christine Galant, Caroline Bouzin, Pierre G Coulie, and Nisha Limaye
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Medicine - Published
- 2021
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8. Prediction of prognosis and renal outcome in lupus nephritis
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Farah Tamirou, Ioannis Parodis, and Frédéric A Houssiau
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Lupus nephritis (LN) is a severe manifestation of SLE, characterised by subendothelial and/or subepithelial immune complex depositions in the afflicted kidney, resulting in extensive injury and nephron loss during the acute phase and eventually chronic irreversible damage and renal function impairment if not treated effectively. The therapeutic management of LN has improved during the last decades, but the imperative need for consensual outcome measures remains. In order to design trials with success potentiality, it is important to define clinically important short-term and long-term targets of therapeutic and non-therapeutic intervention. While it is known that early response to treatment is coupled with favourable renal outcomes, early predictors of renal function impairment are lacking. The information gleaned from kidney biopsies may provide important insights in this direction. Alas, baseline clinical and histopathological information has not been shown to be informative. By contrast, accumulating evidence of pronounced discrepancies between clinical and histopathological outcomes after the initial phase of immunosuppression has prompted investigations of the potential usefulness of per-protocol repeat kidney biopsies as an integral part of treatment evaluation, including patients showing adequate clinical response. This approach appears to have merit. Hopefully, clinical, molecular or genetic markers that reliably reflect kidney histopathology and portend the long-term prognosis will be identified. Novel non-invasive imaging methods and employment of the evolving artificial intelligence in pattern recognition may also be helpful towards these goals. The molecular and cellular characterisation of SLE and LN will hopefully result in novel therapeutic modalities, maybe new taxonomy perspectives, and ultimately personalised management.
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- 2020
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9. Management of Lupus Nephritis
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Farah Tamirou and Frédéric A. Houssiau
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lupus nephritis ,treat-to-target approach ,repeat kidney biopsy ,combination therapy ,Medicine - Abstract
Lupus nephritis (LN) is a frequent and severe manifestation of systemic lupus erythematosus. The main goal of the management of LN is to avoid chronic kidney disease (CKD). Current treatment strategies remain unsatisfactory in terms of complete renal response, prevention of relapses, CKD, and progression to end-stage kidney disease. To improve the prognosis of LN, recent data suggest that we should (i) modify our treat-to-target approach by including, in addition to a clinical target, a pathological target and (ii) switch from conventional sequential therapy to combination therapy. Here, we also review the results of recent controlled randomized trials.
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- 2021
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10. 605 The Systemic Lupus Erythematosus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and Lupus Foundation of America (LFA) Damage Index Revision – Item Generation Phase
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Burak Kundakci, Ann E Clarke, Sindhu R Johnson, Hermine I Brunner, Jiacai Cho, Nathalie Costedoat-Chalumeau, Ellen M Ginzler, John G Hanly, Abida Hasan, Murat Inanç, Naureen Kabani, Kaitlin Lima, Livia Lindoso, Anselm Mak, Rosalind Ramsey- Goldman, Guillermo Ruiz-Irastorza, Clovis A Silva, Farah Tamirou, Vitor C Trindade, Évelyne Vinet, Ian N Bruce, and Megan RW Barber
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- 2022
11. Molecular Signatures of Kidney Antibody–Secreting Cells in Lupus Patients With Active Nephritis Upon Immunosuppressive Therapy
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Etienne Crickx, Selda Aydin, Alexandre Karras, Farah Tamirou, Jean-Claude Weill, Aurélie Hummel, Ailsa Robbins, Claude-Agnès Reynaud, Tatiana Fadeev, Frédéric Houssiau, Bernard Lauwerys, Tessa Huscenot, Nathalie Costedoat-Chalumeau, Matthieu Mahévas, Marion Rabant, Philippe Remy, Véronique Le Guern, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service d'anatomie pathologique, and UCL - (SLuc) Service de rhumatologie
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endocrine system ,Pathology ,medicine.medical_specialty ,animal diseases ,Plasma Cells ,Immunology ,Lupus nephritis ,Renal function ,Urine ,Kidney ,Rheumatology ,Biopsy ,medicine ,Humans ,Immunology and Allergy ,Prospective Studies ,Antibody-Producing Cells ,Systemic lupus erythematosus ,medicine.diagnostic_test ,business.industry ,Gene Expression Profiling ,hemic and immune systems ,Induction Chemotherapy ,medicine.disease ,Lupus Nephritis ,eye diseases ,Treatment Outcome ,medicine.anatomical_structure ,Bone marrow ,business ,Multiplex Polymerase Chain Reaction ,tissues ,Nephritis ,Immunosuppressive Agents ,Follow-Up Studies - Abstract
OBJECTIVE: This study was undertaken to characterize kidney and urine antibody-secreting cells (ASCs) from patients with active lupus nephritis, before and after induction therapy. METHODS: We included patients with biopsy-proven active lupus nephritis and performed anti-CD138 staining of kidney biopsy samples to visualize ASCs. We performed single-cell gene expression profiling on sorted ASCs from fresh biopsy samples using multiplex reverse transcriptase-polymerase chain reaction. We used a gene set that allowed for the study of ASC maturation from plasmablasts to long-lived plasma cells. We quantified urine ASCs from untreated patients with lupus nephritis at diagnosis and after 6 months of prospective follow-up during induction therapy. RESULTS: The number of kidney CD138+ ASCs in 46 untreated patients with lupus nephritis was correlated with a low estimated glomerular filtration rate and with tubulointerstitial damage. Most kidney ASCs from 3 untreated patients had a plasmablast molecular signature; in contrast, in 4 patients with refractory lupus nephritis, the kidney ASCs were mainly long-lived plasma cells, representing an ASC transcriptional profile similar to that in the bone marrow of 2 healthy donors. Some urine ASCs with a plasmablast signature were detected in patients with untreated active lupus nephritis. The presence of urine ASCs at 6 months was associated with treatment failure. CONCLUSION: Our results suggest potential for ASC-directed therapy in refractory lupus nephritis.
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- 2021
12. Worse long-term renal outcome of lupus nephritis patients of African descent living in Europe
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Antoine Enfrein, Valérie Pirson, Véronique Le Guern, Adexandre Karras, Farah Tamirou, Nathalie Costedoat-Chalumeau, and Frederic Houssiau
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Rheumatology ,Creatinine ,Immunology ,Immunology and Allergy ,Humans ,Renal Insufficiency, Chronic ,Kidney ,Lupus Nephritis ,Retrospective Studies ,Hydroxychloroquine - Abstract
IntroductionPrognosis of lupus nephritis (LN) among patients of African descent living in Europe has been understudied.MethodsIn a retrospective study performed in two European university hospitals, we compared the prognosis of LN in patients of African descent or Caucasians. Remission was defined as a urine protein to creatinine (uP/C) ratio1 g/g, leading to a repeat kidney biopsy and/or immunosuppressive treatment change. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate≤60 mL/min/1.73 m2. Adherence was retrospectively assessed through medical files and/or hydroxychloroquine level measurements.Results52 patients of African descent and 85 Caucasian patients were included in this analysis. Class III and isolated class V LN were more common among patients of African descent. Time to first renal remission did not differ between ethnic subgroups. By contrast, patients of African descent suffered from earlier renal flares, CKD was more common and time to CKD was shorter after a flare. In a multivariate analysis, African ancestry was an independent risk factor for progression to CKD. We observed no significant difference in non-adherence to treatment between the two groups.ConclusionLN patients of African descent have worse renal outcomes, mainly explained by a higher rate of renal flare.
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- 2022
13. Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis
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Ioannis Parodis, Farah Tamirou, Julia Weinmann-Menke, Alvaro Gomez, Selda Aydin, Christina Adamichou, Frédéric Houssiau, Nathalie Demoulin, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, UCL - (SLuc) Service d'anatomie pathologique, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, and UCL - SSS/IREC/SLUC - Pôle St.-Luc
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Male ,Biopsy ,030232 urology & nephrology ,Kidney ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,systemic lupus erythematosus ,Recurrence ,Interquartile range ,Pharmacology (medical) ,Proteinuria ,medicine.diagnostic_test ,Hazard ratio ,Prognosis ,Lupus Nephritis ,Kidney Tubules ,Creatinine ,Disease Progression ,histopathology ,Female ,Renal biopsy ,medicine.symptom ,Rituximab ,Immunosuppressive Agents ,Adult ,long-term outcome ,medicine.medical_specialty ,Renal function ,Methylprednisolone ,Young Adult ,03 medical and health sciences ,renal biopsy ,Rheumatology ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,Cyclophosphamide ,Glucocorticoids ,Proportional Hazards Models ,Retrospective Studies ,lupus nephritis ,repeat biopsy ,030203 arthritis & rheumatology ,business.industry ,renal function ,Mycophenolic Acid ,chemistry ,Pulse Therapy, Drug ,Histopathology ,business - Abstract
Objectives In patients with LN, clinical and histological responses to treatment have been shown to be discordant. We investigated whether per-protocol repeat kidney biopsies are predictive of LN relapses and long-term renal function impairment. Methods Forty-two patients with incident biopsy-proven active proliferative (class III/IV±V) LN from the database of the UCLouvain were included in this retrospective study. Per-protocol repeat biopsies were performed after a median [interquartile range (IQR)] time of 24.3 (21.3–26.2) months. The National Institutes of Health activity index (AI) and chronicity index (CI) scores were assessed in all biopsies. Results Despite a moderate correlation between urinary protein/creatinine ratios (UPCR) and AI scores at repeat biopsy (r = 0.48; P = 0.001), 10 patients (23.8%) with UPCR 3). High AI scores (continuous) in repeat biopsies were associated with an increased probability and/or shorter time to renal relapse (n = 11) following the repeat biopsy [hazard ratio (HR) = 1.2, 95% CI: 1.1, 1.3; P = 0.007], independently of proteinuria levels. High CI scores (continuous) in repeat biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR = 1.8, 95% CI: 1.1, 2.9; P = 0.016) through a median (IQR) follow-up time of 131.5 (73.8–178.2) months, being also the case for acute tubulointerstitial inflammation and interstitial fibrosis/tubular atrophy in repeat but not baseline biopsies. Conclusion Our results highlight the usefulness of per-protocol repeat biopsies, herein performed after a median time of 24 months from baseline, as an integral part of the treatment evaluation, also in patients showing adequate clinical response.
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- 2020
14. The added value of a European Reference Network on rare and complex connective tissue and musculoskeletal diseases: insights after the first 5 years of the ERN ReCONNET
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Rosaria Talarico, Silvia Aguilera, Tobias Alexander, Zahir Amoura, Janette Andersen, Laurent Arnaud, Tadej Avcin, Sara Marsal Barril, Lorenzo Beretta, Stefano Bombardieri, Alessandra Bortoluzzi, Coralie Bouillot, Inita Bulina, Gerd R. Burmester, Sara Cannizzo, Lorenzo Cavagna, Benjamin Chaigne, Alain Cornet, Paolo Corti, Nathalie Costedoat-Chalumeau, Zane Dāvidsone, Andrea Doria, Carol Fenech, Alessandro Ferraris, Rebecca Fischer-Betz, João Eurico Fonseca, Charissa Frank, Andrea Gaglioti, Ilaria Galetti, Vera Guimarães, Eric Hachulla, Monica Holmner, Frederic Houssiau, Luca Iaccarino, Søren Jacobsen, Maarten Limper, Fransiska Malfait, Xavier Mariette, Diana Marinello, Thierry Martin, Lisa Matthews, Marco Matucci-Cerinic, Alain Meyer, Jasminka Milas-Ahić, Pia Moinzadeh, Carlomaurizio Montecucco, Luc Mouthon, Ulf Müller-Ladner, György Nagy, Eunice Patarata, Margarita Pileckyte, Chris Pruunsild, Simona Rednic, Vasco C. Romão, Matthias Schneider, Carlo Alberto Scirè, Vanessa Smith, Alberto Sulli, Farah Tamirou, Chiara Tani, Domenica Taruscio, Anna V. Taulaigo, Angela Tincani, Simone Ticciati, Giuseppe Turchetti, P. Martin van Hagen, Jacob M. van Laar, Ana Viera, Jeska K. de Vries-Bouwstra, Johannes Zschocke, Maurizio Cutolo, Marta Mosca, Talarico, R, Aguilera, S, Alexander, T, Amoura, Z, Andersen, J, Arnaud, L, Avcin, T, Marsal Barril, S, Beretta, L, Bombardieri, S, Bortoluzzi, A, Bouillot, C, Bulina, I, Burmester, G, Cannizzo, S, Cavagna, L, Chaigne, B, Cornet, A, Corti, P, Costedoat-Chalumeau, N, Davidsone, Z, Doria, A, Fenech, C, Ferraris, A, Fischer-Betz, R, Fonseca, J, Frank, C, Gaglioti, A, Galetti, I, Guimaraes, V, Hachulla, E, Holmner, M, Houssiau, F, Iaccarino, L, Jacobsen, S, Limper, M, Malfait, F, Mariette, X, Marinello, D, Martin, T, Matthews, L, Matucci-Cerinic, M, Meyer, A, Milas-Ahic, J, Moinzadeh, P, Montecucco, C, Mouthon, L, Muller-Ladner, U, Nagy, G, Patarata, E, Pileckyte, M, Pruunsild, C, Rednic, S, Romao, V, Schneider, M, Scire, C, Smith, V, Sulli, A, Tamirou, F, Tani, C, Taruscio, D, Taulaigo, A, Tincani, A, Ticciati, S, Turchetti, G, van Hagen, P, van Laar, J, Vieira, A, de Vries-Bouwstra, J, Zschocke, J, Cutolo, M, Mosca, M, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
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rare and complex diseases ,Health Personnel ,rare and complex disease ,Immunology ,patient care ,European Reference Network ,rheumatic and musculoskeletal diseases ,rheumatic and musculoskeletal disease ,Europe ,European Reference Networks ,Rare Diseases ,Rheumatology ,Connective Tissue ,connective tissue disease ,Immunology and Allergy ,Humans ,Musculoskeletal Diseases ,connective tissue diseases ,European Commission - Abstract
In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.
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- 2022
15. High p16INK4a, a marker of cellular senescence, is associated with renal injury, impairment and outcome in lupus nephritis
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Frédéric Houssiau, Caroline Bouzin, Bernard Lauwerys, Pierre Coulie, Gaëlle Tilman, Christine Galant, Farah Tamirou, Nisha Limaye, Selda Aydin, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/GECE - Génétique cellulaire, UCL - SSS/DDUV/GEPI - Epigénétique, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service d'anatomie pathologique, and UCL - (SLuc) Service de rhumatologie
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Pathology ,medicine.medical_specialty ,Kidney ,Systemic disease ,Lupus erythematosus ,business.industry ,Autoimmune diseases ,Systemic ,Immunology ,Lupus nephritis ,Renal function ,medicine.disease ,medicine.anatomical_structure ,Rheumatology ,Fibrosis ,medicine ,Renal fibrosis ,Immunology and Allergy ,Medicine ,business ,CD8 - Abstract
ObjectivesBecause a significant fraction of patients with lupus nephritis (LN) develops renal impairment, there is a need to better understand the mechanisms underlying disease progression. Here, we assessed for cellular senescence in the LN kidney, and its association with disease severity and outcome.MethodsWe enumerated the number of cells positive for p16INK4a protein, a marker of cellular senescence, by immunohistochemistry followed by digital quantification, on renal biopsies from 40 patients with active LN. We tested for an association of p16INK4a with renal fibrosis, CD8+ T cell infiltration, systemic disease and renal function at baseline and at 5 years.ResultsThe presence of p16INK4a-positive cells was significantly associated with lower estimated glomerular filtration rate at baseline and 5 years post-treatment, independently of patient demographics and systemic disease parameters. It was also associated with higher baseline renal fibrosis and CD8+ T cell infiltration. Interestingly, we observed marked spatial co-distribution of glomerular p16INK4a-positive cells with CD8+ T cells.ConclusionWe demonstrate, for the first time, that LN biopsies characterised by renal impairment display increased p16INK4a-positive cells, associated with higher fibrosis and CD8+ T cell infiltration. Cellular senescence may represent a kidney-intrinsic disease mechanism and potentially, a novel therapeutic target in LN.
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- 2021
16. Treat-to-Target in Lupus Nephritis. What is the Role of the Repeat Kidney Biopsy?
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Ioannis Parodis, Farah Tamirou, Frédéric A. Houssiau, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
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Biopsy ,Immunology ,Kidney biopsy ,Kidney disorders ,Autoimmunity ,General Medicine ,Kidney ,Lupus Nephritis ,Systemic lupus erythematosus ,Lupus nephritis ,Immunology and Allergy ,Humans ,Kidney Failure, Chronic ,Lupus Erythematosus, Systemic ,Treat-to-target ,Retrospective Studies - Abstract
Kidney involvement, termed lupus nephritis (LN), develops in 35–60% of patients with systemic lupus erythematosus, often early during the disease course. When not treated promptly and efficiently, LN may lead to rapid and severe loss of kidney function, being the reason why it is considered one of the most severe lupus manifestations. Despite improved pharmacotherapy, 5–20% of LN patients develop end-stage kidney disease within ten years from the LN diagnosis. While the principal ground of LN therapy is prevention of renal function worsening, resembling a race against nephron loss, consensual agreement upon outcome measures and clinically meaningful short- and long-term targets of LN therapy have yet to be determined. Literature points to the importance of inclusion of tissue-based approaches in the determination of those targets, and evidence accumulates regarding the importance of per-protocol repeat kidney biopsies in the evaluation of the initial phase of therapy and prediction of long-term renal prognosis. The latter leads to the hypothesis that the information gleaned from repeat biopsies may contribute to optimised therapeutic decision making, and, therefore, increased probability to attain complete renal response in the short term, and a more favourable renal prognosis within a longer prospect. The multinational project ReBioLup was recently designed to serve as a key contributor to form evidence about the role of per-protocol repeat biopsies in a randomised fashion and aspires to unify the global LN community towards improved kidney and patient survival.
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- 2021
17. Publisher Correction: The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET
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Rosaria Talarico, Silvia Aguilera, Tobias Alexander, Zahir Amoura, Ana M. Antunes, Laurent Arnaud, Tadej Avcin, Lorenzo Beretta, Stefano Bombardieri, Gerd R. Burmester, Sara Cannizzo, Lorenzo Cavagna, Benjamin Chaigne, Alain Cornet, Nathalie Costedoat-Chalumeau, Andrea Doria, Alessandro Ferraris, Rebecca Fischer-Betz, João E. Fonseca, Charissa Frank, Andrea Gaglioti, Ilaria Galetti, Jürgen Grunert, Vera Guimarães, Eric Hachulla, Frederic Houssiau, Luca Iaccarino, Thomas Krieg, Marteen Limper, Fransiska Malfait, Xavier Mariette, Diana Marinello, Thierry Martin, Lisa Matthews, Marco Matucci-Cerinic, Alain Meyer, Carlomaurizio Montecucco, Luc Mouthon, Ulf Müller-Ladner, Simona Rednic, Vasco C. Romão, Matthias Schneider, Vanessa Smith, Alberto Sulli, Farah Tamirou, Domenica Taruscio, Anna V. Taulaigo, Enrique Terol, Angela Tincani, Simone Ticciati, Giuseppe Turchetti, P. Martin van Hagen, Jacob M. van Laar, Ana Vieira, Jeska K. de Vries-Bouwstra, Maurizio Cutolo, and Marta Mosca
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Rheumatology - Published
- 2022
18. Comparison of hydroxychloroquine titers measured in frozen/thawed serum and whole blood obtained from lupus patients
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Charlotte Anne Baert, Séverine Nieuwland, Tatiana Sokolova, Farah Tamirou, and Frédéric Houssiau
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Rheumatology ,Humans ,Lupus Erythematosus, Systemic ,Hydroxychloroquine - Published
- 2022
19. High p16
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Gaëlle, Tilman, Caroline, Bouzin, Selda, Aydin, Farah, Tamirou, Christine, Galant, Pierre G, Coulie, Frédéric, Houssiau, Bernard, Lauwerys, and Nisha, Limaye
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lupus nephritis ,Humans ,Lupus ,autoimmune diseases ,CD8-Positive T-Lymphocytes ,systemic ,Kidney ,Cellular Senescence ,Cyclin-Dependent Kinase Inhibitor p16 ,lupus erythematosus - Abstract
Objectives Because a significant fraction of patients with lupus nephritis (LN) develops renal impairment, there is a need to better understand the mechanisms underlying disease progression. Here, we assessed for cellular senescence in the LN kidney, and its association with disease severity and outcome. Methods We enumerated the number of cells positive for p16INK4a protein, a marker of cellular senescence, by immunohistochemistry followed by digital quantification, on renal biopsies from 40 patients with active LN. We tested for an association of p16INK4a with renal fibrosis, CD8+ T cell infiltration, systemic disease and renal function at baseline and at 5 years. Results The presence of p16INK4a-positive cells was significantly associated with lower estimated glomerular filtration rate at baseline and 5 years post-treatment, independently of patient demographics and systemic disease parameters. It was also associated with higher baseline renal fibrosis and CD8+ T cell infiltration. Interestingly, we observed marked spatial co-distribution of glomerular p16INK4a-positive cells with CD8+ T cells. Conclusion We demonstrate, for the first time, that LN biopsies characterised by renal impairment display increased p16INK4a-positive cells, associated with higher fibrosis and CD8+ T cell infiltration. Cellular senescence may represent a kidney-intrinsic disease mechanism and potentially, a novel therapeutic target in LN.
- Published
- 2021
20. Management of Lupus Nephritis
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Frédéric Houssiau, Farah Tamirou, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
- Subjects
Oncology ,medicine.medical_specialty ,Combination therapy ,Lupus nephritis ,lcsh:Medicine ,Review ,law.invention ,repeat kidney biopsy ,combination therapy ,treat-to-target approach ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,030212 general & internal medicine ,Renal response ,Pathological ,030203 arthritis & rheumatology ,lupus nephritis ,business.industry ,lcsh:R ,General Medicine ,medicine.disease ,Treatment strategy ,business ,Kidney disease - Abstract
Lupus nephritis (LN) is a frequent and severe manifestation of systemic lupus erythematosus. The main goal of the management of LN is to avoid chronic kidney disease (CKD). Current treatment strategies remain unsatisfactory in terms of complete renal response, prevention of relapses, CKD, and progression to end-stage kidney disease. To improve the prognosis of LN, recent data suggest that we should (i) modify our treat-to-target approach by including, in addition to a clinical target, a pathological target and (ii) switch from conventional sequential therapy to combination therapy. Here, we also review the results of recent controlled randomized trials.
- Published
- 2021
21. Absence of renal remission portends poor long-term kidney outcome in lupus nephritis
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Antoine Enfrein, Valérie Pirson, Frédéric Houssiau, Farah Tamirou, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
- Subjects
medicine.medical_specialty ,Immunology ,Lupus nephritis ,Renal function ,Brief Communication ,urologic and male genital diseases ,Kidney ,Gastroenterology ,chemistry.chemical_compound ,Internal medicine ,Biopsy ,Medicine ,Humans ,outcome assessment ,Retrospective Studies ,lupus nephritis ,Creatinine ,Lupus erythematosus ,medicine.diagnostic_test ,business.industry ,Systemic ,Health care ,General Medicine ,systemic ,RC581-607 ,medicine.disease ,health care ,Outcome assessment ,medicine.anatomical_structure ,chemistry ,Cohort ,Immunologic diseases. Allergy ,business ,lupus erythematosus ,Kidney disease ,Glomerular Filtration Rate - Abstract
BackgroundThe very long-term consequences of absence of remission in lupus nephritis (LN) remain understudied.MethodsIn this retrospective analysis, we studied a selected cohort of 128 patients with biopsy-proven class III, IV or V incident LN followed for a median period of 134 months (minimum 25). Remission was defined as a urine protein to creatinine (uP:C) ratio 1 g/g, leading to a repeat kidney biopsy and treatment change. Poor long-term renal outcome was defined as the presence of chronic kidney disease (CKD).ResultsTwenty per cent of patients never achieved renal remission. Their baseline characteristics did not differ from those who did. Absence of renal remission was associated with a threefold higher risk of CKD (48% vs 16%) and a 10-fold higher risk of end-stage renal disease (20% vs 2%). Patients achieving early remission had significantly higher estimated glomerular filtration rate (eGFR) at last follow-up compared with late remitters. Accordingly, patients with CKD at last follow-up had statistically longer time to remission. Among patients who achieved remission, 32% relapsed, with a negative impact on renal outcome, that is, lower eGFR values and higher proportion of CKD (33% vs 8%).ConclusionEarly remission should be achieved to better preserve long-term renal function.
- Published
- 2021
22. The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET
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Marteen Limper, Matthias Schneider, Alberto Sulli, Luc Mouthon, Fransiska Malfait, Ulf Müller-Ladner, Jürgen Grunert, Lorenzo Cavagna, Ilaria Galetti, Vanessa Smith, Ana Rita Vieira, Stefano Bombardieri, Marco Matucci-Cerinic, Ana Margarida Antunes, Alessandro Ferraris, Tobias Alexander, Giuseppe Turchetti, Marta Mosca, Laurent Arnaud, Tadej Avcin, Jeska K de Vries-Bouwstra, Thomas Krieg, P. Martin van Hagen, Alain Meyer, Eric Hachulla, Angela Tincani, Silvia Aguilera, Simona Rednic, Sara Cannizzo, Benjamin Chaigne, Thierry Martin, Alain Cornet, Rebecca Fischer-Betz, Xavier Mariette, Luca Iaccarino, Lorenzo Beretta, Diana Marinello, Rosaria Talarico, Vera Guimarães, Nathalie Costedoat-Chalumeau, João Eurico Fonseca, Lisa Matthews, Farah Tamirou, Carlomaurizio Montecucco, Andrea Doria, Vasco C. Romão, Frédéric Houssiau, Jacob M van Laar, Simone Ticciati, Maurizio Cutolo, Anna Viola Taulaigo, Gerd R Burmester, Enrique Terol, Zahir Amoura, Andrea Gaglioti, Charissa Frank, Domenica Taruscio, Repositório da Universidade de Lisboa, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Immunology, and Internal Medicine
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0301 basic medicine ,Telemedicine ,Vulnerability ,Telehealth ,Comorbidity ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,Systemic lupus erythematosus ,Rheumatology ,Antiphospholipid syndrome ,Medicine ,Humans ,Connective Tissue Diseases ,Pandemics ,030203 arthritis & rheumatology ,Health economics ,business.industry ,SARS-CoV-2 ,COVID-19 ,medicine.disease ,Connective tissue disease ,030104 developmental biology ,Sjögren's disease ,Perspective ,Systemic sclerosis ,Medical emergency ,business ,Health impact assessment ,Delivery of Health Care ,Rare disease - Abstract
During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies., In this Perspective article, members of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases discuss clinical and organizational challenges in this community caused by the COVID-19 pandemic and what lessons might be learned for the future.
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- 2020
23. Prediction of prognosis and renal outcome in lupus nephritis
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Ioannis Parodis, Farah Tamirou, and Frédéric Houssiau
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0301 basic medicine ,Male ,lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,medicine.medical_treatment ,Biopsy ,Immunology ,Lupus nephritis ,Renal function ,Review ,Nephron ,Kidney ,outcomes research ,03 medical and health sciences ,0302 clinical medicine ,systemic lupus erythematosus ,Artificial Intelligence ,Outcome Assessment, Health Care ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Renal Insufficiency ,Intensive care medicine ,030203 arthritis & rheumatology ,Immunosuppression Therapy ,business.industry ,Immunosuppression ,General Medicine ,medicine.disease ,Prognosis ,Lupus Nephritis ,Immune complex ,Patient Outcome Assessment ,030104 developmental biology ,medicine.anatomical_structure ,Histopathology ,Female ,Outcomes research ,business ,lcsh:RC581-607 ,Biomarkers - Abstract
Lupus nephritis (LN) is a severe manifestation of SLE, characterised by subendothelial and/or subepithelial immune complex depositions in the afflicted kidney, resulting in extensive injury and nephron loss during the acute phase and eventually chronic irreversible damage and renal function impairment if not treated effectively. The therapeutic management of LN has improved during the last decades, but the imperative need for consensual outcome measures remains. In order to design trials with success potentiality, it is important to define clinically important short-term and long-term targets of therapeutic and non-therapeutic intervention. While it is known that early response to treatment is coupled with favourable renal outcomes, early predictors of renal function impairment are lacking. The information gleaned from kidney biopsies may provide important insights in this direction. Alas, baseline clinical and histopathological information has not been shown to be informative. By contrast, accumulating evidence of pronounced discrepancies between clinical and histopathological outcomes after the initial phase of immunosuppression has prompted investigations of the potential usefulness of per-protocol repeat kidney biopsies as an integral part of treatment evaluation, including patients showing adequate clinical response. This approach appears to have merit. Hopefully, clinical, molecular or genetic markers that reliably reflect kidney histopathology and portend the long-term prognosis will be identified. Novel non-invasive imaging methods and employment of the evolving artificial intelligence in pattern recognition may also be helpful towards these goals. The molecular and cellular characterisation of SLE and LN will hopefully result in novel therapeutic modalities, maybe new taxonomy perspectives, and ultimately personalised management.
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- 2020
24. P102 Senescence of renal resident cells is associated with impaired renal function in lupus nephritis
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Frédéric Houssiau, Gaëlle Tilman, Selda Aydin, Christine Galant, Farah Tamirou, and Bernard Lauwerys
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Senescence ,Pathology ,medicine.medical_specialty ,Kidney ,medicine.diagnostic_test ,business.industry ,Lupus nephritis ,Renal function ,medicine.disease ,Immune system ,medicine.anatomical_structure ,Fibrosis ,medicine ,Renal fibrosis ,Renal biopsy ,business - Abstract
Background Renal fibrosis is a feared complication of Lupus Nephritis (LN), and is associated with irreversible loss of kidney function. In our previous experiments, we found that intrarenal infiltration by immune effectors in LN correlates with the development of renal fibrosis. Here, we wondered whether cellular senescence, through its typical secretome (known as senescence-associated secretory phenotype or SASP) or through the accumulation of functionally incompetent cells, are part of the renal functional impairment and fibrotic process in LN. Methods Microarray data (Illumina HumanHT-2 v4 Expression BeadChip), obtained by our group from 32 human LN kidney biopsies and 8 controls were mined using GeneSpring software in order to study the expression of SASP-associated transcripts. Senescent cells were identified in human LN kidney biopsies using an anti-p16 antibody (Roche Diagnostics). Evaluation of glomerular activity and chronicity indices, glomerular and interstitial fibrosis was performed using conventional or quantitative scores on HE- PAS- and Red Sirius-stained sections. Clinical and biological data were retrieved from the medical files of the patients. Results Mining of microarray data obtained from 32 LN kidney biopsies indicated that SASP-associated transcripts (e.g. IGFB4, VCAM1, TGFb2, COL1A2, MMP7) were significantly overexpressed in kidney biopsies characterized by the presence of adaptive immune cell infiltrates in the interstitium and lower renal function. Expression of SASP-associated transcripts correlated significantly with the expression of b galactosidase (GLB1), a key regulator of the senescence process. In a pilot experiment, we stained LN renal biopsy sections using anti-p16 antibodies, in order to detect the presence of senescent cells. We found a positive stain in podocytes and renal tubular cells from 8 LN patients. The number of positive cells correlated positively with the number of intrarenal CD8-positive cells and the amount of fibrosis in these samples, while it correlated negatively with renal function (eGFR). Conclusion Our data show that the presence of senescent podocytes and renal tubular cells in LN kidney biopsies correlates with fibrotic changes and impaired renal function. Characterization of senescent cells in a larger cohort of LN biopsies is ongoing. Our observations are in line with the hypothesis that inflammation-accelerated senescence links the presence of activated adaptive immune effectors in the lupus kidney and the development of fibrosis.
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- 2020
25. O19 Evolution of kidney antibody secreting cells molecular signature in lupus patients with active nephritis upon immunosuppressive therapy
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Véronique Le Guern, Frédéric Houssiau, Jean-Claude Weill, Marion Rabant, Aurélie Hummel, Farah Tamirou, Philippe Remy, Alexandre Karras, N. Costedoat, Bernard Lauwerys, Matthieu Mahévas, Claude-Agnès Reynaud, Tatiana Fadeev, Tessa Huscenot, and Etienne Crickx
- Subjects
endocrine system ,Kidney ,Pathology ,medicine.medical_specialty ,Systemic lupus erythematosus ,business.industry ,animal diseases ,Cell ,Lupus nephritis ,hemic and immune systems ,Urine ,medicine.disease ,eye diseases ,Gene expression profiling ,medicine.anatomical_structure ,Medicine ,Bone marrow ,business ,tissues ,Nephritis - Abstract
Background/Purpose Pathogenic antibody-secreting cells (ASC) are poorly characterized in human lupus nephritis (LN). Our objective was to compare the single cell molecular signature of ASC in kidney and urine from patients with active LN, either untreated or after immunosuppressive therapy failure. Methods ASC were identified by anti-CD138 staining on fixed renal biopsies from patients with active LN. We sorted single-ASC from fresh renal biopsies to perform gene expression profiling. ASC transcriptional program from urine of untreated LN patients was assessed at diagnosis and after a prospective follow up during induction therapy. Results Interstitial infiltrates of CD138+ ASC were found in untreated (N=15) and refractory patients (N=6). Single cell molecular signature of kidney ASC from untreated patients revealed that these cells were mostly plasmablasts and contrasted with ASC signature from patients with mycophenolate mofetil failure that expressed long-lived plasma cells genes and clustered with long-lived bone marrow ASC from healthy donors. A plasmablast signature was observed in urine ASC at diagnosis, similar to their kidney counterpart. The concentration of urine ASC from 22 untreated patients correlated with ISN/RPS classification, with higher concentration in class IV patients (p Conclusion These results suggest that plasmablasts infiltrate kidney of untreated LN patients, while kidney long-lived ASC may contribute to the failure of immunosuppressive therapy. Acknowledgement This work was funded by FOREUM.
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- 2020
26. O33 Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis
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Ioannis Parodis, Frédéric Houssiau, Selda Aydin, Nathalie Demoulin, Farah Tamirou, Christina Adamichou, Julia Weinmann-Menke, and Alvaro Gomez
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medicine.medical_specialty ,Kidney ,Creatinine ,Proteinuria ,medicine.diagnostic_test ,business.industry ,Lupus nephritis ,Renal function ,Retrospective cohort study ,medicine.disease ,Response to treatment ,Gastroenterology ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Internal medicine ,Biopsy ,medicine ,medicine.symptom ,business - Abstract
Background In patients with Lupus Nephritis (LN), clinical response to treatment and renal histopathology have been shown to be discordant. We investigated whether per-protocol repeat renal biopsies are predictive of LN relapses and long-term impairment of renal function. Methods Forty-two patients with an incident biopsy-proven active proliferative (class III/IV ± V) LN from the LN database of the Universite catholique de Louvain were included in the present retrospective study. Per-protocol repeat kidney biopsies were performed in all patients after a median time of 24.3 (IQR: 21.3–26.2) months. The NIH activity index (AI) and chronicity index (CI) scores were assessed in both baseline and repeat biopsies. Results Despite a moderate correlation between urinary protein/creatinine (U-P/C) ratios and AI scores at repeat biopsy (r=0.48; P=0.001), ten patients (23.8%) with U-P/C ratios 3; figure 1). High AI scores in repeat biopsies were associated with an increased probability and/or shorter time to renal relapse (N=11) following the repeat biopsy (HR: 1.2; 95% CI: 1.1–1.3; P=0.007), independently of proteinuria levels. High NIH CI scores in repeat biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR: 1.8; 95% CI: 1.1–2.9; P=0.016) through a median follow-up time of 131.5 (IQR: 73.8–178.2) months. Baseline AI/CI scores were not predictive of these outcomes. Conclusions Our results highlight the usefulness of per-protocol repeat biopsies as an integral part of the treatment evaluation, also in patients who have shown adequate clinical response.
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- 2020
27. Disease severity of proliferative lupus nephritis in Maghrebians
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N. Costedoat-Chalumeau, Alexandre Karras, Farah Tamirou, Noémie Jourde-Chiche, Michel Jadoul, Eric Hachulla, Eric Daugas, Viviane Gnemmi, Frédéric Houssiau, V. Le Guern, and G. Medkouri
- Subjects
Adult ,Male ,medicine.medical_specialty ,030232 urology & nephrology ,Lupus nephritis ,Kaplan-Meier Estimate ,Kidney ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Africa, Northern ,Rheumatology ,Disease severity ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,030203 arthritis & rheumatology ,Systemic lupus erythematosus ,business.industry ,Outcome measures ,Middle Aged ,medicine.disease ,Lupus Nephritis ,Europe ,Proteinuria ,Treatment Outcome ,ROC Curve ,Creatinine ,Cohort ,Kidney Failure, Chronic ,Female ,business ,Immunosuppressive Agents ,Renal flare ,Glomerular Filtration Rate - Abstract
Objective To study the influence of Maghrebian ethnicity on lupus nephritis. Methods We retrospectively reviewed the files of a cohort of 194 patients with proliferative lupus nephritis followed in seven lupus centres belonging to three groups: Europeans living in Belgium/France (E; n = 111); Maghrebians living in Europe, in casu Belgium/France (ME; n = 43); and Maghrebians living in Morocco (MM; n = 40). Baseline presentation was compared between these three groups but complete long-term outcome data were available only for E and ME patients. Results At presentation, the clinical and pathological characteristics of lupus nephritis did not differ between E, ME and MM patients. Renal relapses were more common in ME patients (54%) than in E patients (29%) ( P Conclusion Despite a similar disease profile at onset, the prognosis of lupus nephritis is more severe in Maghrebians living in Europe compared to native Europeans, with a higher relapse rate.
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- 2018
28. Brief Report: The Euro‐Lupus Low‐Dose Intravenous Cyclophosphamide Regimen Does Not Impact the Ovarian Reserve, as Measured by Serum Levels of Anti–Müllerian Hormone
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Farah Tamirou, Frédéric Debiève, Frédéric Houssiau, Bernard Lauwerys, Damien Gruson, and Séverine Nieuwland Husson
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Adult ,Anti-Mullerian Hormone ,medicine.medical_specialty ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Clinical Protocols ,Rheumatology ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,030212 general & internal medicine ,Ovarian Reserve ,skin and connective tissue diseases ,Ovarian reserve ,Cyclophosphamide ,030203 arthritis & rheumatology ,Systemic lupus erythematosus ,Lupus erythematosus ,biology ,Cumulative dose ,business.industry ,Anti-Müllerian hormone ,medicine.disease ,Regimen ,Titer ,Endocrinology ,biology.protein ,Administration, Intravenous ,Female ,business ,Immunosuppressive Agents ,Hormone - Abstract
Objective The Euro-Lupus regimen of low-dose intravenous cyclophosphamide (IV CYC) (cumulative dose of 3 gm) was developed to reduce gonadal toxicity. To address the possibility of a marginal effect on the ovarian reserve, we measured serum titers of anti-Mullerian hormone (AMH) in patients with systemic lupus erythematosus (SLE) treated with the Euro-Lupus regimen and compared them with those measured in patients who were treated with higher doses of IV CYC or were never treated with IV CYC. Methods Serum AMH levels were measured by enzyme-linked immunosorbent assay in a cohort of 155 premenopausal SLE patients; 30 of these patients had been treated with the Euro-Lupus regimen, and 24 had received higher doses of IV CYC. None had received oral CYC. AMH levels were age-adjusted using a slope computed from levels measured across the group of SLE patients who had not been treated with IV CYC. Demographic and clinical data were collected. Results Serum titers of AMH measured in SLE patients treated with the Euro-Lupus IV CYC regimen (median dose 1.46 ng/ml) did not differ from those measured in patients never treated with the cytotoxic drug (median 1.85 ng/ml). As expected, patients given >6 gm of IV CYC had significantly lower serum titers of AMH (median 0.83 ng/ml) compared with those never treated with IV CYC (P = 0.047). Median serum AMH titers did not change before (1.24 ng/ml) and after (2.50 ng/ml) treatment with the Euro-Lupus IV CYC regimen in the subset of patients for whom paired samples could be tested (P = 0.43). Conclusion The Euro-Lupus regimen of low-dose IV CYC does not impact the ovarian reserve of SLE patients and can therefore be proposed as treatment in patients seeking to become pregnant.
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- 2017
29. Ce que le rhumatologue doit savoir du lupus
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Bernard Lauwerys, Séverine Nieuwland-Husson, Farah Tamirou, and Frédéric Houssiau
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030203 arthritis & rheumatology ,0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Rheumatology - Abstract
RESUME Dans cette mise au point, les auteurs resument une lecture donnee en seance pleniere a l’occasion du 29e Congres de la Societe Francaise de Rhumatologie. Plutot qu’une revue exhaustive des manifestations cliniques du lupus et de son traitement, les auteurs insistent sur les elements essentiels de la prise en charge de cette pathologie complexe et sur quelques points d’actualites. Le but est de rappeler ce que tout rhumatologue doit savoir du lupus en 2016.
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- 2016
30. Correction
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Alain, Meyer, Scire', Carlo Alberto, Rosaria, Talarico, Tobias, Alexander, Zahir, Amoura, Tadej, Avcin, Simone, Barsotti, Lorenzo, Beretta, Jelena, Blagojevic, Gerd, Burmester, Ilaria, Cavazzana, Patrick, Cherrin, Laura, Damian, Andrea, Doria, João Eurico, Fonseca, Furini, Federica, Ilaria, Galetti, Frederic, Houssiau, Thomas, Krieg, Maddalena, Larosa, David, Launay, Raquel, Campanilho-Marques, Thierry, Martin, Marco, Matucci-Cerinic, Pia, Moinzadeh, Carlomaurizio, Montecucco, Maria Francisca, Moraes-Fontes, Luc, Mouthon, Rossella, Neri, Sabrina, Paolino, Yves, Piette, Simona, Rednic, Farah, Tamirou, Angela, Tincani, Natasa, Toplak, Stefano, Bombardieri, Eric, Hachulla, Ulf, Mueller-Ladner, Matthias, Schneider, Vanessa, Smith, Ana, Vieira, Maurizio, Cutolo, Marta, Mosca, and Lorenzo, Cavagna
- Subjects
medicine.medical_specialty ,business.industry ,Immunology ,Correction ,Unmet needs ,NO ,Clinical Practice ,Idiopathic inflammatory myopathies ,Rheumatology ,Immunology and Allergy ,Medicine ,Narrative review ,business ,Intensive care medicine ,Connective Tissue Diseases - Abstract
Idiopathic inflammatory myopathies (IIMs) encompass a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and inflammation, but in antisynthetase syndrome arthritis and interstitial lung disease are more frequent and often inaugurate the disease. Clinical practice guidelines (CPGs) have been proposed for IIMs, but they are sparse and heterogeneous. This work aimed at identifying: i) current available CPGs for IIMs, ii) patients ’ and clinicians’ unmet needs not covered by CPGs. It has been performed in the framework of the European Reference Network on rare and complex connective tissue and musculoskeletal diseases (ReCONNET), a network of centre of expertise and patients funded by the European Union’s Health Programme. Fourteen original CPGs were identified, notably recommending that: i) extra-muscular involvements should be assessed; ii) corticosteroids and methotrexate or azathioprine are first-line therapies of IIMs. ii) IVIG is a treatment of resistant-DM that may be also used in other resistant-IIMs; iii) physical therapy and sun protection (in DM patients) are part of the treatment; v) tumour screening for patients with DM include imaging of chest, abdomen, pelvis and breast (in woman) along with colonoscopy (in patients over 50 years); vi) disease activity and damages should be monitor using standardised and validated tools. Yet, only half of these CPGs were evidence-based. Crucial unmet needs were identified both by patients and clinicians. In particular, there was a lack of large multidisciplinary working group and of patients ’ preferences. The following fields were not or inappropriately targeted: diagnosis; management of extra-muscular involvements other than skin; co-morbidities and severe manifestations.
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- 2019
31. FRI0607 IDENTIFICATION OF UNMET NEEDS RELATED TO RARE AND COMPLEX CONNECTIVE TISSUE AND MUSCULOSKELETAL DISEASES (RCTDS) ACROSS EU: THE EXPERIENCE OF THE ERN RECONNET
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Juergen Grunert, Nathalie Costedoat-Chalumeau, Simona Rednic, Laurent Arnaud, Maarten Limper, Luca Iaccarino, Lisa Matthews, Vera Guimaraes, Rebecca Fischer-Betz, Marta Mosca, Fransiska Malfait, Marco Matucci-Cerinic, Rosaria Talarico, Vanessa Smith, Alain Cornet, Maurizio Cutolo, Ana Rita Vieira, Carlo Alberto Scirè, Xavier Mariette, Farah Tamirou, Simone Ticciati, Charissa Frank, Angela Tincani, Anna Viola Taulaigo, Benjamin Chaigne, Diana Marinello, Ilaria Galetti, Lorenzo Beretta, Tobias Alexander, Alberto Sulli, Vasco C. Romão, Lorenzo Cavagna, and Alain Meyer
- Subjects
030203 arthritis & rheumatology ,0301 basic medicine ,Treatment response ,medicine.medical_specialty ,business.industry ,Network on ,Minor (academic) ,Unmet needs ,Disease activity ,Clinical Practice ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Family medicine ,Medicine ,Psychological aspects ,business ,Healthcare providers - Abstract
Background The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) is a virtual Network that aims to improve and standardize the quality of care offered to rCTDs patients in Europe, empower patients, share knowledge and expertise, enhance research, support efficient use of resources. ERN ReCONNET covers 10 rCTDs: APS, UCTD, Idiopathic Inflammatory myopathies, IgG4, MCTD, Systemic sclerosis, Relapsing Polychondritis, SLE, Sjogren and EDS. Objectives Identification of unmet needs in diagnosis, monitoring and management of rCTDs after literature review of existing clinical practice guidelines (CPGs). Methods After the review of existing CPGs, the most relevant unmet needs, both for clinicians and patients, were identified by discussion among the members of the network. Results A considerable number of unmet needs were identified. In particular, the lack of shared classification criteria, of evidence-based CPGs, validated tools for the assessment of treatment response and disease activity/damage are the major unmet needs especially for the rarest rCTDs. Transversal topics for all rCTDs that need to be addressed are the scarcity of EU/international randomised controlled trials, the identification of patient-reported outcomes and non-adherence to treatment, quality of life indicators, the need to develop composite disease activity scores for all rCTDs and specific (inter)national web-based registries. Patients highlighted the need of a more holistic approach to rCTDs, demanding more attention to pain, fatigue and psychological aspects related to the diseases and the promotion of an early diagnosis. Conclusion The identification of rCTDs unmet needs provided a very useful picture on future actions to be undertaken in order to provide a better care to patients. Many activities are ongoing towards these goals in ERN ReCONNET. These will be possible as a result of a EU collaboration among rCTDs stakeholders, the main added value of ERN ReCONNET. Acknowledgement Thanks to all ERN ReCONNET Steering Committe, Healthcare Providers, ePAGs and Team for huge support. Disclosure of Interests Diana Marinello: None declared, Simone Ticciati: None declared, Rosaria Talarico: None declared, Tobias Alexander: None declared, Laurent Arnaud Consultant for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Paid instructor for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Speakers bureau: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Lorenzo Cavagna: None declared, Lorenzo Beretta: None declared, Benjamin Chaigne: None declared, Alain Cornet Grant/research support from: No direct financial grants from Pharmaceutical companies, but some grants accrued LUPUS EUROPE does, in the form of Grants or payment for attending advisory boards or providing patient views, Speakers bureau: I have been involved in GSK panels to provide patient perspective. However, the minor service fee obtained accrued to LUPUS EUROPE ratyher than the company, Nathalie Costedoat-Chalumeau: None declared, Rebecca Fischer-Betz Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Charissa Hermine Frank: None declared, Ilaria Galetti: None declared, Jurgen Grunert: None declared, vera guimaraes: None declared, Luca Iaccarino: None declared, Maarten Limper Consultant for: GSK, Roche and Thermofisher, Speakers bureau: GSK and Roche, Fransiska Malfait: None declared, Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma, lisa matthews: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen, alain meyer: None declared, Simona Rednic: None declared, Vasco Romao: None declared, Carlo Alberto Scire: None declared, Vanessa Smith: None declared, Alberto Sulli: None declared, Farah Tamirou: None declared, Anna Viola Taulaigo: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Ana Vieira: None declared, Maurizio Cutolo: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB
- Published
- 2019
32. THU0211 EVOLUTION OF KIDNEY ANTIBODY SECRETING CELLS MOLECULAR SIGNATURE IN LUPUS PATIENTS WITH ACTIVE NEPHRITIS UPON IMMUNOSUPPRESSIVE THERAPY
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Frédéric Houssiau, Tessa Huscenot, Jean-Claude Weill, Bertrand Godeau, Ailsa Robbins, Alexandre Karras, Farah Tamirou, Etienne Crickx, Nathalie Costedoat-Chalumeau, Tatiana Fadeev, Bernard Lauwerys, Véronique Le Guern, Aurélie Hummel, Claude-Agnès Reynaud, Matthieu Mahevas, Marion Rabant, and Philippe Remy
- Subjects
030203 arthritis & rheumatology ,0301 basic medicine ,Nephrology ,Pathology ,medicine.medical_specialty ,Kidney ,Systemic lupus erythematosus ,medicine.diagnostic_test ,business.industry ,Lupus nephritis ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Renal pathology ,Internal medicine ,Biopsy ,medicine ,Bone marrow ,business ,Nephritis - Abstract
Background: Pathogenic antibody secreting cells (ASC) have been identified in the kidney of SLE-prone mice, but are poorly characterized in human lupus nephritis (LN). We hypothesized that long-lived plasma cells may contribute to the failure of immunosuppressive therapy in refractory patients. Objectives: To characterize and compare the single cell molecular signature of ASC in kidney and urine from patients with active LN, either untreated or after immunosuppressive therapy failure. Methods: We included patients with biopsy proven active LN from 4 centers and meeting the ACR revised classification criteria for SLE diagnosis. Renal biopsies were scored according to 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, and stained with anti-CD138 to visualize ASC. ASC were single cell sorted as CD3-/CD14-/CD16-/CD27high/CD38high cells. Single-cell gene expression profiling was performed by multiplex RT-PCR using Fluidigm Dynamic Arrays. We used a set of genes derived from a previous transcriptomic analysis of human splenic and bone marrow ASC to distinguish the process of ASC maturation from plasmablast (PB) to long-lived PC. We also studied ASC transcriptional program from urine of untreated LN patients at diagnosis and after 3 and 6 months of a prospective follow up during induction therapy (Plasmo-Lup study). Results: Immunohistochemistry stainings on kidney biopsies from both untreated (N=15) and refractory patients (N=6) showed infiltrates of CD138+ ASC mainly located in the interstitium, particularly in untreated patients. Single cell molecular signature of kidney ASC from 3 untreated patients with class IV LN revealed that these cells were mostly PB expressing multiple genes linked with cell division, and PC without long-lived genes expression. This contrasted with ASC signature from 3 patients with active LN and mycophenolate mofetil (MMF) failure that expressed long-lived PC genes and no proliferative genes. Primary component analysis of 170 single-cells showed clustering of ASC from MMF treated patients with long-lived bone marrow PC from healthy donors that were distinct from PB/PC from untreated patients (Figure 1). A PB signature was observed in urine ASC at diagnosis, similar to their kidney counterpart. The concentration of ASC in urine in 22 untreated patients correlated with ISN/RPS classification, with higher concentration in class IV patients (p Conclusion: These results suggest that PB infiltrate kidney of untreated LN patients, and that kidney long-lived PC may contribute to the failure of immunosuppressive therapy. Acknowledgement: This work was supported by Foreum Disclosure of Interests: None declared
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- 2019
33. Multidisciplinary management of interstitial lung diseases: A real-life study
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Caroline, Biglia, Benoît, Ghaye, Gregory, Reychler, Sandra, Koenig, Halil, Yildiz, Valérie, Lacroix, Farah, Tamirou, Delphine, Hoton, Thierry, Pieters, and Antoine, Froidure
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Male ,Patient Care Team ,Patient Selection ,Clinical Decision-Making ,Middle Aged ,Treatment Outcome ,Predictive Value of Tests ,Risk Factors ,Humans ,Female ,Interdisciplinary Communication ,Cooperative Behavior ,Lung Diseases, Interstitial ,Aged ,Retrospective Studies - Abstract
The guidelines on idiopathic pulmonary fibrosis (IPF) diagnosis established the crucial role of multidisciplinary discussion (MDD) in the diagnosis of interstitial lung diseases (ILD). However, real-life evaluation of MDD remains scarce. Our aim was to study the impact of a well-structured MDD on etiological assessment, diagnosis, and management of ILD.We collected and analysed all relevant data on patients concerning diagnosis and treatment before and after MDD during the year 2017.One hundred fifty patients were included in the analysis. MDD had a significant impact on management: 42% of diagnoses were revised and the number of unclassifiable ILD was significantly reduced. Lung biopsy was performed in 26 patients (12 cryobiopsies and 14 surgical biopsies). The most prevalent diagnoses were connective-tissue disease associated ILD (32%), idiopathic pulmonary fibrosis (23%), hypersensitivity pneumonitis (13%) and granulomatous ILD (7%). MDD led to a change or initiation of treatment in 55% of cases. Nine patients were evaluated for transplantation, 23 patients were screened for academic or sponsored clinical trials and an 8-fold increase in rehabilitation inclusion was observed.Our results confirm the benefits of MDD on ILD management and diagnosis. MDD also facilitates access to non-pharmacological therapies and clinical trials.
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- 2019
34. Idiopathic inflammatory myopathies: state of the art on clinical practice guidelines
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Carlo Alberto Scirè, Thomas Krieg, Nataša Toplak, Pia Moinzadeh, Maurizio Cutolo, Carlomaurizio Montecucco, Ilaria Galetti, David Launay, Marta Mosca, Stefano Bombardieri, Lorenzo Beretta, Matthias F. Schneider, Maddalena Larosa, Thierry Martin, Patrick Cherrin, João Eurico Fonseca, Tobias Alexander, Federica Furini, Maria Francisca Moraes-Fontes, Marco Matucci-Cerinic, Ilaria Cavazzana, Lorenzo Cavagna, Rosaria Talarico, Farah Tamirou, Andrea Doria, Sabrina Paolino, Angela Tincani, Ana Rita Vieira, Ulf Mueller-Ladner, Eric Hachulla, Simone Barsotti, Gerd R Burmester, Zahir Amoura, Laura Damian, Tadej Avcin, Alain Meyer, Simona Rednic, Luc Mouthon, Yves Piette, Raquel Campanilho-Marques, Vanessa Smith, Jelena Blagojevic, Frédéric Houssiau, Rossella Neri, and Repositório da Universidade de Lisboa
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medicine.medical_specialty ,Evidence-based practice ,Immunology ,Azathioprine ,Antisynthetase syndrome ,Disease ,NO ,polymyositis ,03 medical and health sciences ,0302 clinical medicine ,ADULT ,Rheumatology ,intravenous immunoglobulin ,Medicine and Health Sciences ,MYOSITIS ,MANAGEMENT ,medicine ,INTRAVENOUS IMMUNOGLOBULIN ,Immunology and Allergy ,media_common.cataloged_instance ,European union ,Intensive care medicine ,Juvenile dermatomyositis ,media_common ,030203 arthritis & rheumatology ,juvenile dermatomyositis ,business.industry ,adult ,MORTALITY ,Interstitial lung disease ,JUVENILE DERMATOMYOSITIS ,hikers feet ,medicine.disease ,mortality ,Comorbidity ,intravenous immunoglobulin, juvenile dermatomyositis, hikers feet, consensus, myositis, polymyositis, management, adult, mortality, arthritis ,arthritis ,POLYMYOSITIS ,consensus ,HIKERS FEET ,ARTHRITIS ,CONSENSUS ,business ,myositis ,management ,030217 neurology & neurosurgery ,medicine.drug - Abstract
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ, This article has been corrected since it first published. The authors would like to notify that title of the article has been changed to:Idiopathic inflammatory myopathies: state of the art on clinical practice guidelines. RMD Open 2019;5:e000784corr1. doi:10.1136/rmdopen-2018-000784cor, Idiopathic inflammatory myopathies (IIMs) encompass a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and inflammation, but in antisynthetase syndrome arthritis and interstitial lung disease are more frequent and often inaugurate the disease. Clinical practice guidelines (CPGs) have been proposed for IIMs, but they are sparse and heterogeneous. This work aimed at identifying: i) current available CPGs for IIMs, ii) patients’ and clinicians’ unmet needs not covered by CPGs. It has been performed in the framework of the European Reference Network on rare and complex connective tissue and musculoskeletal diseases (ReCONNET), a network of centre of expertise and patients funded by the European Union’s Health Programme. Fourteen original CPGs were identified, notably recommending that: i) extra-muscular involvements should be assessed; ii) corticosteroids and methotrexate or azathioprine are first-line therapies of IIMs. iii) IVIG is a treatment of resistantDM that may be also used in other resistant-IIMs; iv) physical therapy and sun protection (in DM patients) are part of the treatment; v) tumour screening for patients with DM include imaging of chest, abdomen, pelvis and breast (in woman) along with colonoscopy (in patients over 50 years); vi) disease activity and damages should be monitor using standardised and validated tools. Yet, only half of these CPGs were evidence-based. Crucial unmet needs were identified both by patients and clinicians. In particular, there was a lack of large multidisciplinary working group and of patients’ preferences. The following fields were not or inappropriately targeted: diagnosis; management of extra-muscular involvements other than skin; co-morbidities and severe manifestations., This publication was funded by the European Union’s Health Programme (2014-2020), Framework Partnership Agreement number: 739531 – ERN ReCONNET. The content of this publication represents the views of the authors only and it is their sole responsibility; it cannot be considered to reflect the views of the European Commission and/or the Consumers, Health, Agriculture and Food Executive Agency (CHAFEA) or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.
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- 2019
35. Treatment adherence in systemic lupus erythematosus and rheumatoid arthritis: time to focus on this important issue
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Nathalie Costedoat-Chalumeau, Farah Tamirou, Jean-Charles Piette, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
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030203 arthritis & rheumatology ,Focus (computing) ,medicine.medical_specialty ,business.industry ,Treatment adherence ,Disease Management ,medicine.disease ,Arthritis, Rheumatoid ,Treatment Adherence and Compliance ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Rheumatoid arthritis ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Pharmacology (medical) ,030212 general & internal medicine ,business ,Intensive care medicine - Abstract
Treatment adherence in SLE and RA. RA and SLE are both chronic diseases, and non-adherence to treatment impairs their management. Generally, non-adherence rates in chronic diseases are surprisingly high. A Canadian study assessed primary non-adherence in various conditions and found that as many as 31% of the 37 506 first prescriptions were not filled in at all in the 9 months that followed [1]. Figures for the long-term take-up persistence are even worse; the non-adherence at 1 year ranged from 46 to 82% among 167 907 patients treated with drugs including statins and oral antidiabetics [2]. These numbers may be even higher in some countries without health insurance, too few specialists or other access issues. This non-adherence is referred to as unintentional and is strongly associated with social determinants of health (low literacy, inadequate or no health insurance, language discordance between provider and patient). In this editorial, we focus primarily on intentional, including forgetful, non-adherence by RA and SLE patients receiving care. [...]
- Published
- 2017
36. THU0248 GLOMERULAR AND TUBULOINTERSTITIAL LESIONS IN PER-PROTOCOL REPEAT BUT NOT BASELINE KIDNEY BIOPSY PORTEND RELAPSE AND LONG-TERM RENAL FUNCTION IMPAIRMENT, RESPECTIVELY, IN INCIDENT CASES OF PROLIFERATIVE LUPUS NEPHRITIS
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Nathalie Demoulin, Farah Tamirou, Julia Weinmann-Menke, Selda Aydin, C. Adamichou, Ioannis Parodis, Alvaro Gomez, and Frédéric Houssiau
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medicine.medical_specialty ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Disease duration ,Immunology ,Population ,Lupus nephritis ,Renal function ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Internal medicine ,Cohort ,Biopsy ,medicine ,Immunology and Allergy ,Organ involvement ,Statistical analysis ,education ,business - Abstract
Background:In patients with lupus nephritis (LN), clinical response to treatment and renal histopathology have been shown to be discordant. No clinical or laboratory markers have to date been shown to reliably portend renal prognosis, in particular renal function impairment.Objectives:To investigate whether per-protocol repeat renal biopsies are predictive of LN relapses and long-term impairment of renal function.Methods:Forty-two patients with an incident biopsy-proven active proliferative (class III/IV ± V) LN from the LN database of the Université catholique de Louvain were included in the present retrospective study. Per-protocol repeat kidney biopsies were performed in all patients after a median time of 24.3 (IQR: 21.3–26.2) months. The NIH activity index (AI) and chronicity index (CI) scores were assessed in both baseline and repeat biopsies. We defined acute glomerular lesions as cellular proliferation, fibrinoid necrosis or karyorrhexis, cellular crescents, hyaline thrombi or wire loops, and leucocyte infiltration, and chronic glomerular lesions as glomerular sclerosis and fibrous crescents, in alignment with the NIH activity and chronicity indices. Similarly, we defined acute tubulointerstitial lesions as mononuclear cell infiltration and chronic tubulointerstitial lesions as interstitial fibrosis and tubular atrophy.Results:Despite a moderate correlation between urinary protein/creatinine (U-P/C) ratios and AI scores at repeat biopsy (r=0.48; P=0.001), ten patients (23.8%) with U-P/C ratios 3). High AI scores in repeat (but not baseline) kidney biopsies were associated with an increased probability and/or shorter time to renal relapse (N=11) following the repeat biopsy (HR: 1.2; 95% CI: 1.1–1.3; P=0.007), independently of proteinuria levels. This association remained significant for the NIH activity index items within the glomerular but not the tubulointerstitial compartment of the kidney biopsies. High NIH CI scores in repeat (but not baseline) kidney biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR: 1.8; 95% CI: 1.1–2.9; P=0.016) through a median follow-up time of 131.5 (IQR: 73.8–178.2) months, being the case also for acute and chronic tubulointerstitial lesions in repeat but not baseline kidney biopsies.Conclusion:Our results highlight the usefulness of per-protocol repeat biopsies as an integral part of the treatment evaluation, also in patients who have shown adequate clinical response. Glomerular lesions consistent with active renal disease portend LN relapses, while tubulointerstitial lesions consistent with active disease and chronic damage portent long-term renal function impairment.Disclosure of Interests:Ioannis Parodis: None declared, Christina Adamichou: None declared, Selda Aydin: None declared, Alvaro Gomez: None declared, Nathalie Demoulin: None declared, Julia Weinmann-Menke: None declared, Frederic Houssiau Grant/research support from: UCB, Consultant of: GSK, Farah Tamirou: None declared
- Published
- 2020
37. Multidisciplinary management of interstitial lung diseases in a tertiary centre: A prospective study
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Antoine Froidure, Gregory Reychler, Benoît Ghaye, Thierry Pieters, Farah Tamirou, Valérie Lacroix, Delphine Hoton, and Caroline Biglia
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medicine.medical_specialty ,Lung ,medicine.anatomical_structure ,Multidisciplinary approach ,business.industry ,medicine ,Intensive care medicine ,business ,Prospective cohort study - Published
- 2018
38. Systemic lupus erythematosus: state of the art on clinical practice guidelines
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Ricard Cervera, Sabrina Paolino, Angela Tincani, Ulf Mueller-Ladner, Hervé Devilliers, Gerd R Burmester, Zahir Amoura, Fabrizio Conti, Thierry Martin, Marcello Govoni, Laurent Arnaud, Carlo Alberto Scirè, Tadej Avcin, Matthias Schneider, Marta Mosca, Micaela Fredi, Ana Lladó, Carla Macieira, Maria G Tektonidou, Ilaria Galetti, Alain Cornet, Cristina Pamfil, Maurizio Cutolo, Vanessa Smith, Farah Tamirou, Stefano Bombardieri, Laura Massaro, Eric Hachulla, Frédéric Houssiau, Andrea Doria, Micol Frassi, Fonseca João Eurico, Ronald F van Vollenhoven, Rosaria Talarico, Tobias Alexander, Maria Francisca Moraes-Fontes, Sander W. Tas, Chiara Tani, Alessandra Bortoluzzi, N. Costedoat-Chalumeau, Université Catholique de Louvain = Catholic University of Louvain (UCL), Les Hôpitaux Universitaires de Strasbourg (HUS), Azienda Ospedaliero-Universitaria Pisana [Pisa, Italy], Università degli Studi di Ferrara (UniFE), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Clinic Barcelona Hospital Universitari, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Spedali Civili Hospital [Brescia], Centro Hospitalar de Lisboa Central [Portugal], Centro Hospitalar Universitário Lisboa Norte [Lisbon, Portugal] (CHULN), University of Genoa (UNIGE), University of Amsterdam [Amsterdam] (UvA), Amsterdam Rheumatology & Immunology Center - ARC [Amsterdam, the Netherlands] (Amsterdam UMC), National and Kapodistrian University of Athens (NKUA), University of Pisa - Università di Pisa, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Kerckhoff clinic, Partenaires INRAE, Universitätsklinikum Düsseldorf, Universiteit Gent = Ghent University [Belgium] (UGENT), Hôpital Cochin [AP-HP], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli Studi di Ferrara = University of Ferrara (UniFE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli studi di Genova = University of Genoa (UniGe), Universiteit Gent = Ghent University (UGENT), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Tamirou, F, Arnaud, L, Talarico, R, Scire, C, Alexander, T, Amoura, Z, Avcin, T, Bortoluzzi, A, Cervera, R, Conti, F, Cornet, A, Devilliers, H, Doria, A, Frassi, M, Fredi, M, Govoni, M, Houssiau, F, Llado, A, Macieira, C, Martin, T, Massaro, L, Moraes-Fontes, M, Pamfil, C, Paolino, S, Tani, C, Tas, S, Tektonidou, M, Tincani, A, Van Vollenhoven, R, Bombardieri, S, Burmester, G, Eurico, F, Galetti, I, Hachulla, E, Mueller-Ladner, U, Schneider, M, Smith, V, Cutolo, M, Mosca, M, and Costedoat-Chalumeau, N
- Subjects
medicine.medical_specialty ,HCC DAUTOIM ,Immunology ,MEDLINE ,Lupus nephritis ,Lupus ,Guidelines ,AMERICAN-COLLEGE ,DIAGNOSIS ,Systemic Lupus Erythematosus ,Unmet needs ,NO ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,lupu ,Rheumatology ,immune system diseases ,EUROPEAN LEAGUE ,Immunology and Allergy ,Internal medicine ,medicine ,Medicine and Health Sciences ,MANAGEMENT ,030212 general & internal medicine ,EVIDENCE-BASED RECOMMENDATIONS ,Disease management (health) ,Intensive care medicine ,RHEUMATIC-DISEASES ,030203 arthritis & rheumatology ,RISK ,business.industry ,ASSOCIATION ,medicine.disease ,State of the Art ,3. Good health ,Clinical Practice ,EULAR RECOMMENDATIONS ,PREGNANCY ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,business - Abstract
Systemic lupus erythematosus (SLE) is the paradigm of systemic autoimmune diseases characterised by a wide spectrum of clinical manifestations with an unpredictable relapsing-remitting course. The aim of the present work was to identify current available clinical practice guidelines (CPGs) for SLE, to provide their review and to identify physicians' and patients' unmet needs. Twenty-three original guidelines published between 2004 and 2017 were identified. Many aspects of disease management are covered, including global disease management, lupus nephritis and neuropsychiatric involvement, management of pregnancies, vaccinations and comorbidities monitoring. Unmet needs relate with disease management of some clinical manifestations and adherence to treatment. Many patient's unmet needs have been identified starting with faster diagnosis, need for more therapeutic options, guidelines on lifestyle issues, attention to quality of life and adequate education. info:eu-repo/semantics/publishedVersion
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- 2018
39. Idiopathic inflammatory myopathies: state of the art on clinical practice guidelines [corrected]
- Author
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Alain, Meyer, Carlo Alberto, Scirè, Rosaria, Talarico, Tobias, Alexander, Zahir, Amoura, Tadej, Avcin, Simone, Barsotti, Lorenzo, Beretta, Jelena, Blagojevic, Gerd, Burmester, Ilaria, Cavazzana, Patrick, Cherrin, Laura, Damian, Andrea, Doria, João Eurico, Fonseca, Federica, Furini, Ilaria, Galetti, Frederic, Houssiau, Thomas, Krieg, Larosa, Maddalena, David, Launay, Raquel, Campanilho-Marques, Thierry, Martin, Marco, Matucci-Cerinic, Pia, Moinzadeh, Carlomaurizio, Montecucco, Maria Francisca, Moraes-Fontes, Luc, Mouthon, Rossella, Neri, Sabrina, Paolino, Yves, Piette, Simona, Rednic, Farah, Tamirou, Angela, Tincani, Natasa, Toplak, Stefano, Bombardieri, Eric, Hachulla, Ulf, Mueller-Ladner, Matthias, Schneider, Vanessa, Smith, Ana, Vieira, Maurizio, Cutolo, Marta, Mosca, Lorenzo, Cavagna, UCL - (SLuc) Service de rhumatologie, and UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales
- Subjects
HCC DAUTOIM ,Idiopathic inflammatory myopathies ,Clinical practice guidelines ,State of the art - Abstract
Idiopathic inflammatory myopathies (IIMs) encompass a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and inflammation, but in antisynthetase syndrome arthritis and interstitial lung disease are more frequent and often inaugurate the disease. Clinical practice guidelines (CPGs) have been proposed for IIMs, but they are sparse and heterogeneous. This work aimed at identifying: i) current available CPGs for IIMs, ii) patients ' and clinicians' unmet needs not covered by CPGs. It has been performed in the framework of the European Reference Network on rare and complex connective tissue and musculoskeletal diseases (ReCONNET), a network of centre of expertise and patients funded by the European Union's Health Programme. Fourteen original CPGs were identified, notably recommending that: i) extra-muscular involvements should be assessed; ii) corticosteroids and methotrexate or azathioprine are first-line therapies of IIMs. ii) IVIG is a treatment of resistant-DM that may be also used in other resistant-IIMs; iii) physical therapy and sun protection (in DM patients) are part of the treatment; v) tumour screening for patients with DM include imaging of chest, abdomen, pelvis and breast (in woman) along with colonoscopy (in patients over 50 years); vi) disease activity and damages should be monitor using standardised and validated tools. Yet, only half of these CPGs were evidence-based. Crucial unmet needs were identified both by patients and clinicians. In particular, there was a lack of large multidisciplinary working group and of patients ' preferences. The following fields were not or inappropriately targeted: diagnosis; management of extra-muscular involvements other than skin; co-morbidities and severe manifestations. info:eu-repo/semantics/publishedVersion
- Published
- 2018
40. SAT0238 Glucocorticoid withdrawal in an inception cohort of lupus nephritis patients
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Frédéric Houssiau, S Wautier, Farah Tamirou, and S. Nieuwland-Husson
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medicine.medical_specialty ,Creatinine ,Proteinuria ,Cyclophosphamide ,business.industry ,Lupus nephritis ,medicine.disease ,Gastroenterology ,chemistry.chemical_compound ,T-group ,Methylprednisolone ,chemistry ,Internal medicine ,medicine ,Analysis of variance ,medicine.symptom ,business ,Glucocorticoid ,medicine.drug - Abstract
Background Few studies have addressed glucocorticoid (GC) withdrawal in lupus nephritis (LN). Yet, this remains a pivotal issue due to GC-induced side effects on the one hand, and to the risk of relapse on the other hand. Objectives We reviewed the data of the Louvain Lupus Nephritis Inception Cohort (LOULUNIC) i): to determine the percentage of patients able to permanently or transiently stop GC; ii): to compare their baseline and follow-up characteristics to patients who never stopped; and iii): to assess the consequences of GC withdrawal. Methods Ninety patients with new-onset biopsy-proven LN were included. All were under the care of the same senior physician (FAH) during follow-up. Clinical, pathological and biological data were extracted from our data base. The SLICC/ACR-DI was assessed at last visit. Unpaired t-tests, Mann-Whitney tests and ANOVA were used, as appropriate. Results Out of 90 patients with incident LN, 43 (48%) ever stopped GC (group E), of which 32 permanently (group P). Median time to stop GC was 37 months. 47 patients (52%) never stopped GC (group N). At baseline, serum creatinine, uP/C ratio, ISN/RPS classes, activity and chronicity indices did not differ between groups, nor did the mean initial dose of methylprednisolone (MP) (N: 28 mg/d; E: 32 mg/d; P: 31 mg/d), the use of IV MP pulses (82 and 77% in N and E groups, respectively) and of IV cyclophosphamide (81 and 77%, respectively). During the first year, mean (SD) uP/C decreased statistically more in group E compared to group N (p=0.028 by ANOVA), with striking differences at month 3 (N: 1.73±1.87; E: 0.96±1.34; p=0.038 by unpaired t-test). This difference at month 3 was also noticed for group P patients (0.85±0.76; p=0.02 by unpaired t-test). Interestingly, the mean MP dose at month 3 was statistically higher in group E (19±8) and P (20±9) compared to group N (15±6) (p=0.005 by unpaired t-test). At last follow-up, serum creatinine was statistically lower in E and P patients compared to N patients. Eight of the 11 patients from the T group suffered form a renal relapse, justifying restart of GC, after a median time of 30 months. Importantly, SLICC/ACR-DI was significantly lower in E and P patients, compared to N patients (p=0.0068 and 0.0027, respectively). Conclusions In half of LN patients, complete GC withdrawal is achievable and in one third it can be maintained long term. As expected, patients able to stop GC display less damage at last followup. Patients who were able to stop GC decreased their proteinuria much more promptly during the first year of treatment. Interestingly, they received more GC within the first 3 months of therapy, thereby suggesting that a higher dose of GC during the first 3 months of treatment might be associated with a higher probability of later GC withdrawal. Disclosure of Interest None declared
- Published
- 2017
41. OP0265 A 24-Hour Proteinuria Cutoff Level of 0.7 Gram After 12 Months of Treatment Best Predicts Long-Term Renal Outcome in Lupus Nephritis: Data from the Maintain Nephritis Trial
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Bernard Lauwerys, Maria Dall'Era, Brad H. Rovin, Farah Tamirou, Frédéric Houssiau, Ricard Cervera, and Meggan Mackay
- Subjects
medicine.medical_specialty ,Creatinine ,Proteinuria ,Receiver operating characteristic ,business.industry ,Immunology ,Lupus nephritis ,Urology ,Area under the curve ,Renal function ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Confidence interval ,Surgery ,chemistry.chemical_compound ,Rheumatology ,chemistry ,medicine ,Immunology and Allergy ,medicine.symptom ,business ,Nephritis - Abstract
Background Data from the Euro-Lupus Nephritis Trial (ELNT) indicated that a proteinuria Objectives The current analysis is aimed at testing the validity of this proteinuria cutoff level in another lupus nephritis (LN) patient population, taking advantage of the long-term MAINTAIN Nephritis Trial data set (2). Methods The MAINTAIN Nephritis Trial is an European-based randomized trial performed in 105 LN patients comparing azathioprine and mycophenolate mofetil as maintenance therapy, after induction with low-dose Euro-Lupus intravenous cyclophosphamide. Renal relapse rate was similar in the two groups and early proteinuria decrease within the first year predicted long-term renal function (2). For this analysis, aimed at defining the best cutoff proteinuria level, we selected patients with at least 7 years of follow-up for whom proteinuria measurement was available at month 3 (n=81), 6 (n=80) or 12 (n=80). Good and poor long-term renal outcome was defined as serum creatinine ≤1mg/dl and >1mg/dl at last follow-up, respectively. Sensitivity and specificity were calculated for each proteinuria level, as predictor of good long-term renal outcome. Receiver Operating Characteristic (ROC) curves (area under the curve; AUC) were drawn and the best proteinuria cutoff value at each time point was determined based on Youden index. 95% confidence intervals (CI) were calculated. Results The best proteinuria cutoff value ( i. e. the point on the ROC curve furthest to the equality line, defined by Youden index) at month 3, 6 and 12 is indicated in the Table below, as well as their sensitivity and specificity (±95%CI) as predictor of good renal outcome. The AUCs (between 0.73 and 0.78) confirmed accuracy of the test. A proteinuria cutoff of 0.7g/day optimized sensitivity and specificity at month 12. Quite interestingly, this value is very close to the 0.8g/day at month 12 computed from the ELNT data (1). Conclusions A 24-hour proteinuria cutoff level of 0.7 gram after 12 months of treatment best predicts long-term renal outcome in LN, confirming the ELNT data. We suggest that this target value be used as primary outcome in LN induction trials. References Dell9Ara M et al. Predictors of Long-Term Renal Outcome in Lupus Nephritis Trials: Lessons Learned from the Euro-Lupus Nephritis Cohort. Arthritis Rheumatol 2015; in press. Tamirou F et al. Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis. Ann Rheum Dis 2015; in press. Disclosure of Interest None declared
- Published
- 2015
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