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Systemic Lupus Erythematosus: HELP
Articles by David Alan Isenberg
Based on 171 articles published since 2009
(Why 171 articles?)
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Between 2009 and 2019, D. Isenberg wrote the following 171 articles about Lupus Erythematosus, Systemic.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7
1 Guideline The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. 2018

Gordon, Caroline / Amissah-Arthur, Maame-Boatemaa / Gayed, Mary / Brown, Sue / Bruce, Ian N / D'Cruz, David / Empson, Benjamin / Griffiths, Bridget / Jayne, David / Khamashta, Munther / Lightstone, Liz / Norton, Peter / Norton, Yvonne / Schreiber, Karen / Isenberg, David / Anonymous541089. ·Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham. · Rheumatology Department, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust. · Rheumatology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham. · Royal National Hospital for Rheumatic Diseases, Bath. · Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, University of Manchester, Manchester Academic Health Sciences Centre. · The Kellgren Centre for Rheumatology, NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester. · Louise Coote Lupus Unit, Guy's Hospital, London. · Laurie Pike Health Centre, Modality Partnership, Birmingham. · Department of Rheumatology, Freeman Hospital, Newcastle upon Tyne. · Department of Medicine, University of Cambridge. · Lupus and Vasculitis Unit, Addenbrooke's Hospital, Cambridge. · Lupus Research Unit, The Rayne Institute, St Thomas' Hospital. · Division of Women's Health, King's College London. · Section of Renal Medicine and Vascular Inflammation, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London. · LUPUS UK, Romford, Essex. · Centre for Rheumatology, University College London, London, UK. ·Rheumatology (Oxford) · Pubmed #29029350.

ABSTRACT: -- No abstract --

2 Guideline The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults: Executive Summary. 2018

Gordon, Caroline / Amissah-Arthur, Maame-Boatemaa / Gayed, Mary / Brown, Sue / Bruce, Ian N / D'Cruz, David / Empson, Benjamin / Griffiths, Bridget / Jayne, David / Khamashta, Munther / Lightstone, Liz / Norton, Peter / Norton, Yvonne / Schreiber, Karen / Isenberg, David / Anonymous14430923. ·Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham. · Rheumatology Department, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust. · Rheumatology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham. · Royal National Hospital for Rheumatic Diseases, Bath. · Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, University of Manchester, Manchester Academic Health Sciences Centre. · The Kellgren Centre for Rheumatology, NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester. · Louise Coote Lupus Unit, Guy's Hospital, London. · Laurie Pike Health Centre, Modality Partnership, Birmingham. · Department of Rheumatology, Freeman Hospital, Newcastle upon Tyne. · Department of Medicine, University of Cambridge. · Lupus and Vasculitis Unit, Addenbrooke's Hospital, Cambridge. · Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London. · Division of Women's Health, King's College London. · Section of Renal Medicine and Vascular Inflammation, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London. · LUPUS UK, Romford, Essex. · Centre for Rheumatology, University College London, London, UK. ·Rheumatology (Oxford) · Pubmed #29029296.

ABSTRACT: -- No abstract --

3 Guideline Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. 2014

van Vollenhoven, Ronald F / Mosca, Marta / Bertsias, George / Isenberg, David / Kuhn, Annegret / Lerstrøm, Kirsten / Aringer, Martin / Bootsma, Hendrika / Boumpas, Dimitrios / Bruce, Ian N / Cervera, Ricard / Clarke, Ann / Costedoat-Chalumeau, Nathalie / Czirják, László / Derksen, Ronald / Dörner, Thomas / Gordon, Caroline / Graninger, Winfried / Houssiau, Frédéric / Inanc, Murat / Jacobsen, Søren / Jayne, David / Jedryka-Goral, Anna / Levitsky, Adrian / Levy, Roger / Mariette, Xavier / Morand, Eric / Navarra, Sandra / Neumann, Irmgard / Rahman, Anisur / Rovensky, Jozef / Smolen, Josef / Vasconcelos, Carlos / Voskuyl, Alexandre / Voss, Anne / Zakharova, Helena / Zoma, Asad / Schneider, Matthias. ·Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases, Stockholm, Sweden, Karolinska Institutet, , Stockholm, Sweden. ·Ann Rheum Dis · Pubmed #24739325.

ABSTRACT: The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE.

4 Guideline Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. 2012

Bertsias, George K / Tektonidou, Maria / Amoura, Zahir / Aringer, Martin / Bajema, Ingeborg / Berden, Jo H M / Boletis, John / Cervera, Ricard / Dörner, Thomas / Doria, Andrea / Ferrario, Franco / Floege, Jürgen / Houssiau, Frederic A / Ioannidis, John P A / Isenberg, David A / Kallenberg, Cees G M / Lightstone, Liz / Marks, Stephen D / Martini, Alberto / Moroni, Gabriela / Neumann, Irmgard / Praga, Manuel / Schneider, Matthias / Starra, Argyre / Tesar, Vladimir / Vasconcelos, Carlos / van Vollenhoven, Ronald F / Zakharova, Helena / Haubitz, Marion / Gordon, Caroline / Jayne, David / Boumpas, Dimitrios T / Anonymous430733. ·Department of Medicine, Rheumatology, Clinical Immunology and Allergy, University of Crete, Iraklion, Greece. ·Ann Rheum Dis · Pubmed #22851469.

ABSTRACT: OBJECTIVES: To develop recommendations for the management of adult and paediatric lupus nephritis (LN). METHODS: The available evidence was systematically reviewed using the PubMed database. A modified Delphi method was used to compile questions, elicit expert opinions and reach consensus. RESULTS: Immunosuppressive treatment should be guided by renal biopsy, and aiming for complete renal response (proteinuria <0.5 g/24 h with normal or near-normal renal function). Hydroxychloroquine is recommended for all patients with LN. Because of a more favourable efficacy/toxicity ratio, as initial treatment for patients with class III-IV(A) or (A/C) (±V) LN according to the International Society of Nephrology/Renal Pathology Society 2003 classification, mycophenolic acid (MPA) or low-dose intravenous cyclophosphamide (CY) in combination with glucocorticoids is recommended. In patients with adverse clinical or histological features, CY can be prescribed at higher doses, while azathioprine is an alternative for milder cases. For pure class V LN with nephrotic-range proteinuria, MPA in combination with oral glucocorticoids is recommended as initial treatment. In patients improving after initial treatment, subsequent immunosuppression with MPA or azathioprine is recommended for at least 3 years; in such cases, initial treatment with MPA should be followed by MPA. For MPA or CY failures, switching to the other agent, or to rituximab, is the suggested course of action. In anticipation of pregnancy, patients should be switched to appropriate medications without reducing the intensity of treatment. There is no evidence to suggest that management of LN should differ in children versus adults. CONCLUSIONS: Recommendations for the management of LN were developed using an evidence-based approach followed by expert consensus.

5 Editorial Why, why, why de-lupus (does so badly in clinical trials). 2016

Isenberg, David A / Merrill, Joan T. ·a Centre for Rheumatology, Department of Medicine , University College London , London , UK. · b Clinical Pharmacology Research Program , Oklahoma Medical Research Foundation , Oklahoma City , OK , USA. ·Expert Rev Clin Immunol · Pubmed #26786849.

ABSTRACT: -- No abstract --

6 Editorial Towards treating lupus nephritis without oral steroids: a dream-come-true? 2013

Houssiau, Frédéric A / Isenberg, David. · ·Ann Rheum Dis · Pubmed #23828303.

ABSTRACT: -- No abstract --

7 Editorial Rhubarb and reliability -- a Jane Austen view of systemic lupus erythematosus. 2013

Isenberg, David A. · ·J Rheumatol · Pubmed #23280162.

ABSTRACT: -- No abstract --

8 Editorial Meryl Streep and the problems of clinical trials. 2012

Isenberg, David A. · ·Arthritis Res Ther · Pubmed #22494430.

ABSTRACT: -- No abstract --

9 Editorial Clinical trials in lupus: what have we learned so far? 2010

Bruce, Ian N / Gordon, Caroline / Merrill, Joan T / Isenberg, David. · ·Rheumatology (Oxford) · Pubmed #20123955.

ABSTRACT: -- No abstract --

10 Review An evaluation of voclosporin for the treatment of lupus nephritis. 2018

Sin, Fang En / Isenberg, David. ·a Rheumatology Department , University College Hospital London , London , UK. · b Centre for Rheumatology, Division of Medicine , University College London , London , UK. ·Expert Opin Pharmacother · Pubmed #30207816.

ABSTRACT: INTRODUCTION: Lupus nephritis (LN) is associated with significant morbidity and mortality. Current treatment outcomes remain suboptimal. No disease modifying medications are licensed for the treatment of LN. Voclosporin, a novel calcineurin inhibitor, has been investigated as induction therapy in LN in combination with myocophenolate mofetil (MMF) and a glucocorticoid (GC). Two phase II trials of voclosporin were the first trials of a potential treatment of active LN that met their primary endpoints. Areas covered: This article reviews the pharmacology of voclosporin and the efficacy and safety data from the two existing phase II trials. In the phase IIb randomized controlled trial AURA-LV, voclosporin was shown to be superior to placebo, when used in combination with MMF (1-2 g/day) and GC, in achieving remission in active LN. Expert opinion: While the positive outcome of existing trials is promising, further data confirming its efficacy and evaluating its safety are required. A phase III trial is currently recruiting. Importantly, the positive results were achieved despite a novel and rapid GC taper regime, suggesting that rapid taper of GC may be a viable treatment option in active LN which merits further investigation.

11 Review A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). 2017

van Vollenhoven, Ronald / Voskuyl, Alexandre / Bertsias, George / Aranow, Cynthia / Aringer, Martin / Arnaud, Laurent / Askanase, Anca / Balážová, Petra / Bonfa, Eloisa / Bootsma, Hendrika / Boumpas, Dimitrios / Bruce, Ian / Cervera, Ricard / Clarke, Ann / Coney, Cindy / Costedoat-Chalumeau, Nathalie / Czirják, László / Derksen, Ronald / Doria, Andrea / Dörner, Thomas / Fischer-Betz, Rebecca / Fritsch-Stork, Ruth / Gordon, Caroline / Graninger, Winfried / Györi, Noémi / Houssiau, Frédéric / Isenberg, David / Jacobsen, Soren / Jayne, David / Kuhn, Annegret / Le Guern, Veronique / Lerstrøm, Kirsten / Levy, Roger / Machado-Ribeiro, Francinne / Mariette, Xavier / Missaykeh, Jamil / Morand, Eric / Mosca, Marta / Inanc, Murat / Navarra, Sandra / Neumann, Irmgard / Olesinska, Marzena / Petri, Michelle / Rahman, Anisur / Rekvig, Ole Petter / Rovensky, Jozef / Shoenfeld, Yehuda / Smolen, Josef / Tincani, Angela / Urowitz, Murray / van Leeuw, Bernadette / Vasconcelos, Carlos / Voss, Anne / Werth, Victoria P / Zakharova, Helena / Zoma, Asad / Schneider, Matthias / Ward, Michael. ·Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), Karolinska Institutet, D1:00 Karolinska University Hospital, Solna, Stockholm, Sweden. · Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The Netherlands. · Department of Rheumatology, Clinical Immunology and Allergy, University of Crete School of Medicine, Iraklion, Greece. · Feinstein Institute for Medical Research, Manhasset, New York, USA. · Department of Medicine III, University Medical Center TU Dresden, Dresden, Germany. · New York University, New York, USA. · LPRe SR-Klub Motýlik, Bratislava, Slovakia. · Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. · Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Department of Medicine and Joint Academic Rheumatology Program Medical School, National and Kapodestrian University of Athens, Athens, Greece. · NIHR Manchester Biomedical Research Unit, The University of Manchester and Central Manchester Foundation Trust, Manchester, UK. · Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Catalonia, Spain. · Division of Rheumatology, The Arthritis Society Chair in Rheumatic Diseases Cumming School of Medicine University of Calgary, Calgary, Alberta, Canada. · Lupus Foundation of America, Washington DC, USA. · Université Paris-Decartes, Paris, France. · AP-HP, Hôpital Cochin, service de médecine interne, centre de reference maladies auto-immunes et systémiques rares, Paris, France. · Department of Rheumatology and Immunology, Institute of Bioanalysis, Institute of Family Medicine, University of Pécs, Pécs, Hungary. · Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary. · Department Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands. · Rheumatology Unit, Department of Medicine, University of Padova, Padova, Italy. · Department Medicine/Rheumatology and Clinical Immunology, Charite Universitätsmedizin Berlin, Berlin, Germany. · Polyclinic of Rheumatology, Hiller Research Unit, University Clinic Duesseldorf, Heinrich-Heine-University, Duesseldorf, Germany. · Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. · Division of Rheumatology, Medical University of Graz, Graz, Austria. · Service de Rhumatologie, Cliniques universitaires Saint-Luc, Pôle de pathologies rhumatismales inflammatoires et systémiques, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Bruxelles, Belgium. · Department of Medicine, The Centre for Rheumatology, University College London, UK. · Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Copenhagen, Denmark. · Department of Medicine, University of Cambridge, Cambridge, UK. · Interdisciplinary Center for Clinical Trials (IZKS), University Medical Center Mainz, Mainz, Germany. · LUPUS EUROPE, co-opted trustee for research, Essex UK. · Rheumatology Department, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. · Université Paris-Sud; Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-sud; INSERM U1184, Le Kremlin Bicêtre, France. · Bone Densitometry Unit, Monla Hospital, Tripoli, Lebanon. · Monash University, Faculty of Medicine, Nursing & Health Sciences, Monash Medical Centre, Clayton, Australia. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. · Department of Internal Medicine, Division of Rheumatology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey. · University of Santo Tomas, Manila, Philippines. · Vasculitis.at, Vienna, Austria. · Department of Connective Tissues Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland. · Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · RNA and Molecular Pathology Research Group, Institute of Medical Biology, Health Science Faculty, University of Tromsø, Tromsø, Norway. · National Institute for Rheumatic Diseases, Piešťany, Slovak Republic. · Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center (Affiliated to Tel-Aviv University), Tel-Aviv, Israel. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria. · Dipartimento di Scienze Cliniche e Sperimentali, Università degli Studi di Brescia, U.O. Reumatologia e Immunolgia Clinica, Spedali Civili di Brescia, Brescia, Italy. · Centre for Prognosis Studies in the Rheumatic Diseases, Senior Scientist Krembil Research Institute, Professor Medicine, University of Toronto, Toronto Western Hospital EW 1-409, Toronto, Canada. · Unidade de Imunologia Clínica, Hospital Santo António, Centro Hospitalar do Porto, UMIB, Instituto de Ciencias Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal. · Department of Rheumatology, Odense University Hospital, University of Southern Denmark, Denmark. · Corporal Michael J. Crescenz VA Medical Center (Philadelphia), Philadelphia, Philadelphia, USA. · Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA. · Nephrology Unit, City Clinical Hospital n.a. S.P. Botkin, Moscow, Russia. · Lanarkshire Centre for Rheumatology, Hairmyres Hospital, Scotland, UK. · National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. ·Ann Rheum Dis · Pubmed #27884822.

ABSTRACT: OBJECTIVES: Treat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE. METHODS: An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%. RESULTS: The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: CONCLUSIONS: The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.

12 Review Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis. 2017

Mota, Pedro / Reddy, Venkat / Isenberg, David. ·a Department of Internal Medicine , Hospital da Luz , Lisbon , Portugal. · b Centre for Rheumatology, Division of Medicine , University College London , London , UK. ·Expert Rev Clin Immunol · Pubmed #27841031.

ABSTRACT: INTRODUCTION: Rituximab-based B-cell depletion (BCD) therapy is effective in refractory rheumatoid arthritis (RA) and although used to treat patients with refractory systemic lupus erythematosus (SLE) in routine clinical practice, rituximab failed to meet the primary endpoints in two large randomised controlled trials (RCTs) of non-renal (EXPLORER) and renal (LUNAR) SLE. Areas covered: We review how BCD could be improved to achieve better clinical responses in RA and SLE. Insights into the variability in clinical response to BCD in RA and SLE may help develop new therapeutic strategies. To this end, a literature search was performed using the following terms: rheumatoid arthritis, systemic erythematosus lupus, rituximab and B-cell depletion. Expert commentary: Poor trial design may have, at least partly, contributed to the apparent lack of response to BCD in the two RCTs of patients with SLE. Enhanced B-cell depletion and/or sequential therapy with belimumab may improve clinical response at least in some patients with SLE.

13 Review The diagnosis and management of the haematologic manifestations of lupus. 2016

Velo-García, Alba / Castro, Sara Guerreiro / Isenberg, David A. ·Internal Medicine Department, University Hospital Complex of Pontevedra, Pontevedra, Spain. Electronic address: alba.velo@gmail.com. · Autoimmune Diseases Unit, Internal Medicine 7.2 Department, Hospital Curry Cabral, Centro Hospitalar Lisboa Central, Lisbon, Portugal. Electronic address: saragcastro@gmail.com. · Department of Rheumatology, University College London, UK. Electronic address: d.isenberg@ucl.ac.uk. ·J Autoimmun · Pubmed #27461045.

ABSTRACT: Haematological manifestations in systemic lupus erythematosus (SLE) are frequently observed. They are diverse and range from mild to severe. Therefore, different treatment approaches are needed from simply keeping vigilant to significant immunosuppression. Most treatment evidence is based on case-reports or small retrospective studies, as few randomized controlled trials have been performed. The development of biological therapy has opened new possible ways to treat the most severe cases but further clinical trials are necessary. In this review we consider the most common and characteristic haematological manifestations of SLE patients, focusing on their pathogenesis and management.

14 Review Autoimmune gastrointestinal complications in patients with systemic lupus erythematosus: case series and literature review. 2016

Alves, S Custódio / Fasano, S / Isenberg, D A. ·Internal Medicine Unit, Department of Medicine, Hospital de Cascais, Cascais, Portugal. · Rheumatology Unit, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy. · Centre for Rheumatology, Department of Medicine, University College London, London, UK d.isenberg@ucl.ac.uk. ·Lupus · Pubmed #27329649.

ABSTRACT: The association of systemic lupus erythematosus (SLE) with gastrointestinal autoimmune diseases is rare, but has been described in the literature, mostly as case reports. However, some of these diseases may be very severe, thus a correct and early diagnosis with appropriate management are fundamental. We have analysed our data from the SLE patient cohort at University College Hospital London, established in 1978, identifying those patients with an associated autoimmune gastrointestinal disease. We have also undertaken a review of the literature describing the major autoimmune gastrointestinal pathologies which may be coincident with SLE, focusing on the incidence, clinical and laboratory (particularly antibody) findings, common aetiopathogenesis and complications.

15 Review The safety of pharmacological treatment options for lupus nephritis. 2016

Velo-García, Alba / Ntatsaki, Eleana / Isenberg, David. ·a Internal Medicine Department , University Hospital Complex of Pontevedra , Pontevedra , Spain. · b Centre for Rheumatology, Division of Medicine , University College London , UK. ·Expert Opin Drug Saf · Pubmed #27159360.

ABSTRACT: INTRODUCTION: The management of lupus nephritis (LN) has changed significantly over the last 10 years due to emerging evidence from large randomised clinical trials that produced good quality data and guided the formulation of two key concepts: the induction of remission and the maintenance phase of immunosuppressive therapy. AREAS COVERED: Optimizing cyclophosphamide and glucocorticoid regimens and the introduction of mycophenolate mofetil for proliferative and membranous LN has been pivotal. Nevertheless, concerns remain about treatment toxicity especially long term glucocorticoid use and exposure to cumulative cyclophosphamide doses. Here we discuss the conventional and newer pharmacological options for managing LN focusing on drug safety and toxicity issues. EXPERT OPINION: The need for effective and less toxic treatments led to the development of the role of targeted biologic therapies in LN. However, evidence from the initial randomized controlled trials has been disappointing, although this reflects inadequate trial design rather than true lack of efficacy.

16 Review DNA-damaging autoantibodies and cancer: the lupus butterfly theory. 2016

Noble, Philip W / Bernatsky, Sasha / Clarke, Ann E / Isenberg, David A / Ramsey-Goldman, Rosalind / Hansen, James E. ·Department of Therapeutic Radiology, Yale School of Medicine, 15 York Street, New Haven, Connecticut 06520, USA. · Department of Medicine, Divisions of Rheumatology and Clinical Epidemiology, McGill University, 687 Avenue des Pins Quest, Montreal, Quebec H3A 1A1, Canada. · Division of Rheumatology, Department of Medicine, Cumming School of Medicine, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada. · Centre for Rheumatology, Department of Medicine, Rayne Building, 5 University Street, University College London, London WC1E 6JF, UK. · Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, 240 East Huron Street, Chicago, Illinois 60611, USA. · Yale Cancer Center, Yale School of Medicine, 15 York Street, New Haven, Connecticut 06520, USA. ·Nat Rev Rheumatol · Pubmed #27009542.

ABSTRACT: Autoantibodies reactive against host DNA are detectable in the circulation of most people with systemic lupus erythematosus (SLE). The long-held view that antibodies cannot penetrate live cells has been disproved. A subset of lupus autoantibodies penetrate cells, translocate to nuclei, and inhibit DNA repair or directly damages DNA. The result of these effects depends on the microenvironment and genetic traits of the cell. Some DNA-damaging antibodies alone have little impact on normal cells, but in the presence of other conditions, such as pre-existing DNA-repair defects, can become highly toxic. These findings raise new questions about autoimmunity and DNA damage, and reveal opportunities for new targeted therapies against malignancies particularly vulnerable to DNA damage. In this Perspectives article, we review the known associations between SLE, DNA damage and cancer, and propose a theory for the effects of DNA-damaging autoantibodies on SLE pathophysiology and cancer risk.

17 Review From BILAG to BILAG-based combined lupus assessment-30 years on. 2016

Murphy, Claire-Louise / Yee, Chee-Seng / Gordon, Caroline / Isenberg, David. ·Centre for Rheumatology, University College London, London, ClaireLouise.Murphy@uclh.nhs.uk. · Doncaster and Bassetlaw Hospitals NHS Foundation Trust, Department of Rheumatology, Doncaster Royal Infirmary, Doncaster and. · Rheumatology Research Group (East Wing), School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. · Centre for Rheumatology, University College London, London. ·Rheumatology (Oxford) · Pubmed #26589244.

ABSTRACT: Disease activity in SLE can be difficult to measure and there is no biomarker that uniformly reflects disease activity. There are various disease activity scores, but there is no gold standard assessment tool. This is a review of the development of the BILAG index from the classic BILAG disease activity index to the BILAG-2004 disease activity index and composite response criteria. The original classic BILAG index was revised and distinguished nine organs/systems. Features that indicated damage, such as avascular necrosis, were excluded. There was improvement in the glossary, scoring system and software. The BILAG-2004 index has been shown to be reliable, valid and sensitive to change. The BILAG-2004 index has been modified for pregnancy and has also been used in paediatrics. The SLE Responder Index (SRI) and the BILAG-based combined lupus assessment (BICLA) are composite responder indices incorporating the BILAG index. Since the initial development of the BILAG index in 1984, major improvements have been made in the measurement of disease activity in lupus. However, the BILAG-2004 index is the only transitional index that grades clinical features as being new, the same, worse or improving and incorporates severity in the scoring.

18 Review What can we learn from systemic lupus erythematosus pathophysiology to improve current therapy? 2015

Vilas-Boas, Andreia / Bakshi, Jyoti / Isenberg, David A. ·a 1 Internal Medicine Department, Hospital Pedro Hispano, Matosinhos, Portugal. · b 2 Centre for Rheumatology, University College London Hospitals, London, UK. ·Expert Rev Clin Immunol · Pubmed #26389850.

ABSTRACT: Systemic lupus erythematosus is an autoimmune disorder that can affect every organ system and cause a wide range of signs and symptoms. The precise pathogenic mechanism of disease remains uncertain, but it is clearly complex and involves the activation and deregulation of many components of the immune system. Certain well-characterized patterns of immune pathology are shared by a significant subset of patients and selective targeting of one or more of the key immune system molecules offers the prospect of more effective treatment. This review addresses the current and future treatment for patients with lupus, going from the lessons learnt with pathophysiologic studies to recent clinical trials with biological agents.

19 Review Risk factors for renal disease in systemic lupus erythematosus and their clinical implications. 2015

Ntatsaki, Eleana / Isenberg, David. ·University College London Medical School, Room GF/664, Royal Free Hospital, London NW3 2 PF, UK. ·Expert Rev Clin Immunol · Pubmed #25973642.

ABSTRACT: Lupus nephritis is one of the most common severe manifestations of systemic lupus erythematosus and is associated with significant morbidity and mortality. Genetic, ethnic and hormonal factors may influence the presence and severity of renal involvement and therefore affect the outcome and overall prognosis of patients. In this review, we will discuss the association of known lupus risk factors in developing renal disease and explore the recent literature to identify potential risk factors and their clinical implications in terms of diagnostic vigilance, management and prognosis.

20 Review Profile of atacicept and its potential in the treatment of systemic lupus erythematosus. 2015

Cogollo, Estefania / Silva, Marta Amaral / Isenberg, David. ·Department of Internal Medicine, Hospital Distrital da Figueira da Foz, Coimbra, Portugal. · Centre for Rheumatology, Department of Medicine, University College London, London, UK. ·Drug Des Devel Ther · Pubmed #25834391.

ABSTRACT: The importance of B cell activating factors in the generation of autoantibodies in patients with systemic lupus erythematosus (SLE) is now recognized. The two key factors, known as BAFF and APRIL, produced by a variety of cells including monocytes, dendritic cells and T cells, also help to regulate B cell maturation, function and survival. Biologic agents that block these factors have now been developed and tried out in large scale clinical trials in SLE patients. Benlysta which blocks BAFF has met some of its end points in clinical trials and is approved for use in patients with skin and joint disease who have failed conventional drugs. In contrast, clinical trials using atacicept which blocks both BAFF and APRIL have been more challenging to interpret. An early study in lupus nephritis was, mistakenly, abandoned due to serious infections thought to be linked to the biologic when in fact the dramatic fall in the immunoglobulin levels took place when the patients were given mycophenolate, prior to the introduction of the atacicept. Likewise the higher dose arm (150 mgm) of a flare prevention study was terminated prematurely when 2 deaths occurred. However, the mortality rate in this study was identical to that seen in the Benlysta studies and a post hoc analysis found a highly significant benefit for the 150mgm arm compared to the lower dose (75 mgm) and placebo arms. Other trials with both Benlysta and atacicept are on-going.

21 Review Systemic lupus erythematosus. 2014

Lisnevskaia, Larissa / Murphy, Grainne / Isenberg, David. ·Oshawa Clinic, Oshawa, ON, Canada. · Centre for Rheumatology, Department of Medicine, University College London Hospital, London, UK. · Centre for Rheumatology, Department of Medicine, University College London Hospital, London, UK. Electronic address: d.isenberg@ucl.ac.uk. ·Lancet · Pubmed #24881804.

ABSTRACT: Systemic lupus erythematosus is a remarkable and challenging disorder. Its diversity of clinical features is matched by the complexity of the factors (genetic, hormonal, and environmental) that cause it, and the array of autoantibodies with which it is associated. In this Seminar we reflect on changes in its classification criteria; consider aspects of its more serious clinical expression; and provide a brief review of its aetiopathogenesis, major complications, coping strategies, and conventional treatment. Increased understanding of the cells and molecules involved in the development of the diseases has encouraged the identification of new, better targeted biological approaches to its treatment. The precise role of these newer therapies remains to be established.

22 Review Why and how should we measure disease activity and damage in lupus? 2014

Feld, Joy / Isenberg, David. ·Carmel and Lin medical centres, Rheumatology Unit, Haifa, Israel. · Centre for Rheumatology, Department of Medicine, University Collage London, London, United Kingdom. Electronic address: d.isenberg@ucl.ac.uk. ·Presse Med · Pubmed #24791651.

ABSTRACT: The assessment of disease activity and flare and differentiating them from permanent damage in patients with SLE is challenging. The SLEDAI, SLEDAI-2K and SELENA-SLEDAI measure global disease activity. The BILAG measures organ-specific activity. The BILAG better captures the change in the different organs at the expense of complexity. The SRI is a composite index incorporating both BILAG and SLEDAI indices and a physician's global assessment. It has been used in the most recent clinical trials. Damage correlates with prognosis; it is assessed by the SLICC/SDI index. This index scores damage whatever the cause, disease or treatment related, or the consequence of concomitant disease. The disease activity and damage indices do not correlate well with the patient's health related quality of life (HRQoL), the degree of disability or the impact of disease. The impact of the patients' joint disease on their HRQoL is assessed via the HAQ questionnaire and the global health status via the SF-36 index, or one of the more recently described lupus specific quality of life indices [Lupus QoL]. The global assessment instruments and the BILAG index can also be used in children and adolescents with SLE. However, a modified paediatric version of the SLICC/SDI damage index is advised. Many advances have been achieved in disease activity and damage measurement in the past 20 years but the problem of how best to capture flare accurately remains.

23 Review Drug-induced lupus: Including anti-tumour necrosis factor and interferon induced. 2014

Araújo-Fernández, S / Ahijón-Lana, M / Isenberg, D A. ·1Department of Internal Medicine, Hospital Povisa, Vigo, Spain. ·Lupus · Pubmed #24557776.

ABSTRACT: Drug-induced lupus erythematosus is defined as a syndrome with clinical and serological features similar to systemic lupus erythematosus that is temporally related to continuous drug exposure and which resolves after discontinuation of this drug. More than 90 drugs, including biological modulators such as tumour necrosis factor-α inhibitors and interferons, have been identified as likely 'culprits'. While there are no standard diagnostic criteria for drug-induced lupus erythematosus, guidelines that can help to distinguish drug-induced lupus erythematosus from systemic lupus erythematosus have been proposed and several different patterns of drug-induced lupus erythematosus are emerging. Distinguishing drug-induced lupus erythematosus from systemic lupus erythematosus is important because the prognosis of drug-induced lupus erythematosus is usually good when the drug is withdrawn. This review discusses the differences between drug-induced lupus erythematosus and systemic lupus erythematosus, the mechanisms of action of drug-induced lupus erythematosus and drugs that are usually associated with drug-induced lupus erythematosus, with particular focus on the biological treatments.

24 Review Pathology of systemic lupus erythematosus: the challenges ahead. 2014

Azevedo, Pedro Correia / Murphy, Grainne / Isenberg, David A. ·Internal Medicine Department, Hospital Garcia de Orta, EPE, Almada, Portugal. ·Methods Mol Biol · Pubmed #24497350.

ABSTRACT: Many studies have explored the pathology of systemic lupus erythematosus (SLE), an autoimmune rheumatic disorder with a striking female predominance. Numerous autoimmune phenomena are present in this disease, which ultimately result in organ damage. However, the specific cellular and humoral mechanisms underlying the immune dysfunction are not yet fully understood. It is postulated that autoimmunity is based on the interaction of genetic predisposition, hormonal and environmental triggers that result in reduced tolerance to self-tissues. These phenomena could occur because of altered antigen presentation, abnormalities in B cell responses, increases in the function of T-helper cells, abnormal cytokine production, exaggerated effector responses, or loss of regulatory T cells or B cells. Abnormalities in all of these components of the immune response have been implicated to varying degrees in the pathogenesis of SLE. This chapter will attempt to provide a "state-of-the-art" review of the evidence about the mechanisms underlying the pathology of SLE.

25 Review Recent developments in the treatment of patients with systemic lupus erythematosus: focusing on biologic therapies. 2014

Fattah, Zozik / Isenberg, David A. ·University College Hospital, Department of Rheumatology , 3rd floor central, 250 Euston Road, London, NW1 2PG , UK. ·Expert Opin Biol Ther · Pubmed #24387632.

ABSTRACT: INTRODUCTION: Major trials hoping to obtain optimal disease control in systemic lupus erythematosus (SLE) are ongoing. Given its complex aetiology and pathogenesis, it is not surprising that multiple therapeutic targets have emerged and that none are uniformly successful. AREAS COVERED: In this review, we highlight the recent, more significant studies focusing on the use of biologic therapies. There has been great emphasis on the role of B cells in SLE and many uncontrolled studies have encouraged the use of rituximab (an anti-CD20 monoclonal). Disappointingly, two major trials, EXPLORER and LUNAR did not confirm its utility, although doubts have been expressed on their trial design, and other trials using this drug are commencing. In contrast, belimumab, which blocks a B-cell activating factor, did meet its end points in two major randomised controlled clinical trials and has been approved for use in SLE by both the FDA and the European Medicines Agency. Encouraging, albeit preliminary, results with epratuzumab (which blocks CD22) have also been reported. EXPERT OPINION: In addition to targeting B cells, other approaches including biologics, which modulate T-cell function and block interleukin-6 and interferon-α, have been explored. Finally, we review the recent developments in the use of conventional drugs, such as cyclophosphamide and mycophenolate.

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