Xavier Montalban Barcelona, Spain

Transcription

1 Abstract book 2012 CME Annual meeting in multiple sclerosis MS: from disease management to patient management Valencia, Spain May 2012

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3 Dear Colleague On behalf of the Serono Symposia International Foundation we are delighted to welcome you to the 2012 annual continuing medical education (CME) accredited meeting: MS: from disease management to patient management. At this meeting, leading international experts will come together to discuss current and future approaches to the treatment of multiple sclerosis (MS). You will also have the opportunity to earn CME credits. This interactive meeting is divided into four sessions. Session 1 will cover the pharmacological targets of current and possible future therapies, and the requirement for close safety monitoring of newer therapies. In session 2 we will detail how the neurologist can best use the tools available for optimal diagnosis of MS and prediction of disease course. Session 3 will focus on current and future techniques to predict and monitor response to treatment, and in session 4 we will discuss the clinical management of MS, the relationship with the patient and how this can affect treatment adherence. Case studies will be presented, offering you the opportunity to discuss various aspects of clinical practice with the panel of experts. The aims of the 2012 annual conference are to provide an update on the latest understanding of MS pathophysiology and the mechanisms of action of current drugs, to discuss how best to diagnose patients and then predict and monitor treatment response, and to provide guidance on how best to ensure patients get optimal benefit from treatment. We anticipate that this programme will provide valuable updates for the clinician, and will stimulate engaging and enlightened debate on many of the complex issues surrounding the management of patients with MS. We look forward to your active participation. Yours sincerely, David Bates Newcastle upon Tyne, UK Xavier Montalban Barcelona, Spain All Serono Symposia International Foundation programmes are organized solely to promote the exchange and dissemination of scientific and medical information. No forms of promotional activities are permitted. All Serono Symposia International Foundation programmes are made possible thanks to educational grants received from: Celgene, Centre d Esclerosi Multiple de Catalunya, ComtecMed, Congrex Sweden, Congrex Switzerland, Cryo-Save, Datanalysis, Esaote, European Society of Endocrinology, Fondazione Humanitas, Fundación IVI, ISFP International Society for Fertility Preservation, ISMH International Society of Men s Health, K.I.T.E., Merck Serono, Sanofi-Aventis, University of Catania, Vall d'hebron University Hospital. 1

4 AIM OF THE CONFERENCE LEARNING OBJECTIVES TARGET AUDIENCE ACCREDITATION Research into the pathophysiology of multiple sclerosis (MS) and the mechanism of action of new drugs has, in recent years, produced a virtuous circle offering ever-new insights, enhancing our understanding of the disease and allowing optimization of treatment. The 2012 Serono Symposia International Foundation (SSIF) annual meeting will provide a review of these insights and offer the opportunity to discuss how to translate this increasing knowledge of management improvements for individual patients. By attending the conference, participants will: be able to cite the latest research on MS pathophysiology and modes of action of individual drugs be able to consistently apply standardized diagnostic criteria in daily practice improve their patients treatment adherence via improved skills in sharing information be able to list present and future biomarkers of response to treatment. Clinicians involved in MS management. Serono Symposia International Foundation ( is accredited by the European Accreditation Council for Continuing Medical Education (EACCME ) to provide the following CME activity for medical specialists. The EACCME is an institution of the European Union of Medical Specialists (UEMS), The 2012 CME annual meeting in multiple sclerosis: MS: from disease management to patient management to be held in Valencia, Spain on May 2012, is designated for a maximum of 9 (nine) hours of European CME credits (ECMEC). Each medical specialist should claim only those credits that he/she actually spent in the educational activity. EACCME credits are recognized by the American Medical Association towards the Physician's Recognition Award (PRA). To convert EACCME credit to AMA PRA category 1 credit, please contact the AMA. 2

5 LEARNING EFFECTIVENESS PROJECT The world of CME is changing with many different live and online formats, and Serono Symposia International Foundation (SSIF) is continually trying to improve its CME activities. With your participation in a structured series of evaluations, SSIF can provide cutting-edge learning activities designed to give you the greatest value from the time you invest. SSIF is running the learning effectiveness project for this meeting. During the conference you will be asked to answer some questions to evaluate your knowledge and opinions on the specific topics that will be covered in these two days. We also kindly ask you to assess the program in various domains such as whether you were satisfied with the meeting, whether it met the stated learning objectives, whether the contents were neutral and will be applicable to your daily practice. After the event, you will be involved in two additional steps: Post-event: three weeks after the event we will you a short questionnaire which will give you the opportunity to tell us how much of what you learned has had an affect on your know-how and daily practice. Follow-up: three-months after the event, we will contact you with the final questionnaire. We will collate and analyse your responses and use the results to improve and develop our ongoing programs. Of course, we commit to maintaining the confidentiality of the information you provide and we will inform you about the results of the process regarding the activity that you attended. Thank you very much for participating in this project! follow us on SSIF_Neurology 3

6 VENUE Meliá Valencia Palacio de Congresos Avenida Cortes Valencianas 52 Valencia, Spain LANGUAGE CHAIRS The official language of the conference will be English. David Bates Department of Neurology Royal Victoria Infirmary Newcastle upon Tyne, UK Xavier Montalban Multiple Sclerosis Centre of Catalonia Unit of Clinical Neuroimmunology Vall d Hebron University Hospital Barcelona, Spain SCIENTIFIC SECRETARIAT Serono Symposia International Foundation Salita San Nicola da Tolentino, 1/B Rome, Italy Neurology Team Leader: Serena Dell Ariccia Associate Project Manager: Alessia Addessi Phone: +39 (0) /591 Fax: +39 (0) info@seronosymposia.org ORGANIZING SECRETARIAT Meridiano Congress International Via Mentana, 2/B Rome, Italy Congress Coordinator: Debora Urbinelli Phone: +39 (0) d.urbinelli@meridiano.it 4

7 Scientific programme

8 Day 1 Friday 18 May 2012 SESSION I SSIF Opening G. Comi (Italy) Local welcome B. Casanova (Spain) Welcome and introduction D. Bates (UK) and X. Montalban (Spain) Pharmacological targets and evolving pathophysiological concepts D. Bates (UK) L1 Improving understanding of mechanism of action of immunomodulatory drugs B. Kieseier (Germany) L2 Neuroprotection and steps towards neuroregeneration: promising therapeutic targets R. Gold (Germany) L3 Resetting the immune system: stem cell transplantation A. Uccelli (Italy) L4 Efficacy profiles of MS drugs G. Comi (Italy) L5 Monitoring drug safety in clinical practice P. Vermersch (France) L5 Coffee break 6

9 SESSION II MS Diagnosis and prognosis X. Montalban (Spain) L6 McDonald criteria 2010: making the diagnosis easier A.J. Thompson (UK) L7 The diagnosis of MS before MS M. Tintorè (Spain) L8 What can magnetic resonance imaging tell us about disease evolution in the individual patient? D. Arnold (Canada) L5 Lunch C1 Case study: Differential diagnosis - neuromyelitis optica vs MS Presenter: P. Rieckmann (Germany) Discussant: L. Moiola (Italy) SESSION III Treatment monitoring G. Comi (Italy) L90 Biomarkers G. Giovannoni (UK) L10 MRI as a potential marker of treatment response in current clinical practice A. Rovira (Spain) L11 Present and future roles of pharmacogenomics J. Oksenberg (USA) L11 Coffee break L12 Assessment of treatment response M.S. Freedman (Canada) C2.. Case study: Treatment and treatment algorithms Presenter: G. Comi (Italy) Discussants: X. Montalban and O. Fernández (Spain) L11 End of the day 7

10 Day 2 Saturday 19 May 2012 SESSION IV From disease management to patient management B. Casanova (Spain) L13 The patient s willingness to take risk P. Rieckmann (Germany) L14 How to implement the patient caregiver partnership in clinical practice D. Langdon (UK) L15 Treatment adherence: how to measure it and how to improve it J. Sastre-Garriga (Spain) L11 Coffee break C3.. Case study: Treatment failure due to lack of adherence Presenter: D. Langdon (UK) Discussants: P. Rieckmann (Germany) and J. Sastre-Garriga (Spain) C4.. Case study: Improved outcomes through tailored treatment Presenter: D. Bates (UK) Discussants: G. Giovannoni (UK) and P. Rieckmann (Germany) L11 Concluding remarks L11 End of the conference and closing lunch 8

11 Douglas Arnold David Bates Bonaventura Casanova Giancarlo Comi Oscar Fernández Mark S. Freedman Gavin Giovannoni Ralf Gold Bernd C. Kieseier Dawn Langdon Lucia Moiola Xavier Montalban Jorge Oksenberg Peter Rieckmann Alex Rovira Jaume Sastre-Garriga Alan J. Thompson Mar Tintorè Antonio Uccelli Patrick Vermersch Faculty members

12 Biographies David Bates Chair / Chairman: Session I / Presenter: Session IV Department of Neurology Royal Victoria Infirmary Newcastle upon Tyne, UK David Bates trained in Medicine at Downing College, Cambridge and the Middlesex Hospital, London and in Neurology at the University of Newcastle upon Tyne and the Mayo Clinic, Rochester, Minnesota, USA. He is Emeritus Professor of Clinical Neurology at the University of Newcastle upon Tyne, Former Editor of the International MS Journal and past Chairman of both the MS Forum and the Medical Research Advisory Committee of the MS Society of Great Britain and Northern Ireland. He is Chairman of the Joint Colleges Working Party on the Vegetative State and Criteria for Brain Stem Death and Chairman of the Consensus Conference on the Epilepsies for the Royal College of Physicians, Edinburgh. His research interests are in vascular disease, coma and the unconscious patient, and in MS. Professor Bates has published more than 150 peer-reviewed papers, edited three textbooks and contributed chapters to more than 20. His current research involvement is predominantly in clinical trials of novel therapy in MS and in the role of mitochondria in protecting and repairing axons in the more chronic phases of that disease. Xavier Montalban Chair / Chairman: Session II / Discussant: Session III Multiple Sclerosis Center of Catalonia Unit of Clinical Neuroimmunology Vall d Hebron University Hospital, Barcelona, Spain Xavier Montalban is Chair of the Department of Neurology-Neuroimmunology and Director of the Multiple Sclerosis Center of Catalonia, Vall d Hebron University Hospital, Barcelona, Spain and Professor of Neurology of the University Autònoma de Barcelona. Dr Montalban gained his MD in 1983 and was awarded a PhD in 1988, after formal training in neurology. In 1989 he undertook a postdoctoral research fellowship at Lupus Research Unit at St Thomas Hospital, London, UK, returning to Barcelona in 1990 to create the Unit of Clinical Neuroimmunology and research laboratory. Dr Montalban is a member of a number of scientific organizations, Vice President of the Multiple Sclerosis Foundation, and sits on the advisory board and scientific committee of the Multiple Sclerosis International Federation, the European School of Neuroimmunology and the European Charcot Foundation. Dr Montalban is the current Director for neuroimmunology contents of Revista de Neurología, a publication distributed to over 12,000 professionals. He is also a member of several editorial boards of both national and international specialist journals. He has published over 250 original contributions in international journals and has authored a number of book chapters. Since 2003 he is a member of the advisory committee on clinical trials of new agents for the National Multiple Sclerosis Society, USA. Since 2009 he is a member of the executive committee of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). His current research interests include prognostic factor and biomarkers, immune mechanisms in MS, cognitive dysfunction in MS, new intervention strategies, genetic characterization and pharmacogenomics treatment response. He has participated in both the design and the execution of several Phase II/III clinical trials, and is a member of safety and steering committees. 10

13 Douglas Arnold Speaker: Session II Montreal Neurological Institute and Hospital Montreal, Canada Douglas Arnold is currently a Professor in the Department of Neurology and Neurosurgery at McGill University, Director of the Magnetic Resonance Spectroscopy Unit in the Brain Imaging Center at the Montreal Neurological Institute, and President of NeuroRx Research, a CNS imaging CRO. He has special expertise in advanced magnetic resonance imaging (MRI) acquisition and analysis techniques, particularly as they relate to understanding the evolution of MS and neurodegeneration. Dr Arnold combines advanced image processing of conventional structural images with non-conventional MRI acquisition techniques, such as magnetization transfer imaging and magnetic resonance spectroscopy, to understand how inflammation in MS relates to injury to myelin and neurons. He also uses these techniques to understand how new therapies for MS affect the pathobiology of the disease. Dr Arnold received his medical degree from Cornell University. He completed his residency in neurology at McGill University and a post-doctoral fellowship in magnetic resonance at the University of Oxford. Bonaventura Casanova Chairman: Session IV Department of Neurology University Hospital La Fe Valencia, Spain Bonaventura Casanova has been a specialist in Neurology at Hospital Universitari i Politècnic la Fe de Valencia, Spain, since 1991 and is an Associate Professor of Neurology at the University of Valencia, Spain. Professor Casanova received his MD from the University of Valencia in Following this, he continued his professional training at Servei Valencià de Salut in Valencia from 1988 to 1991, and in 2001 received his PhD from the University of Valencia. He has authored more than 30 publications in neurology within the last 6 years and participated in six research projects as Principal Investigator and/or investigator collaborator. He has also contributed to more than 20 Phase II IV clinical trials. 11

14 Biographies Giancarlo Comi SSIF Scientific Committee President / Speaker: Session I / Chairman: Session III / Presenter: Session III Department of Neurology Institute of Experimental Neurology Vita-Salute San Raffaele University, Milan, Italy Giancarlo Comi received his degree in medicine in 1973 and neurological certification in 1977, both from the University of Milan, Italy. He joined the Department of Neurology, Scientific Institute San Raffaele, University of Milan, in 1974 as a Clinical Assistant and in 1988 was appointed Assistant Professor in Clinical Neurophysiology. Currently he is Professor of Neurology, Chairman of the Department of Neurology, and Director of the Institute of Experimental Neurology at Vita-Salute San Raffaele University, Scientific Institute San Raffaele, Milan. Professor Comi s areas of interest are principally directed towards the study of the pathophysiology and treatment of MS. He has authored and co-authored more than 800 articles in peer-reviewed journals and edited eight books. He has a long-standing involvement as an active member of the steering committees and advisory boards of many international clinical trials, mainly in the field of MS. Professor Comi is the Vice President of the European Charcot Foundation and member of the Board of Administration of the Italian Multiple Sclerosis Foundation and the Scientific Committee of the Italian Multiple Sclerosis Association. Professor Comi has also served as President of the European Neurological Society and the Italian Society of Clinical Neurophysiology. He is currently the President of the Italian Society of Neurology. Professor Comi currently sits on the executive boards of various scientific associations and on the editorial boards of Clinical Neurophysiology, European Neurology and Multiple Sclerosis and is the Associate Editor of Neurological Sciences. Oscar Fernández Discussant: Session III Department of Neurology Hospital Regional Universitario Carlos Haya Malaga, Spain Oscar Fernández is Head of the Department of Neurology, Hospital Regional Universitario Carlos Haya, Malaga, Spain, a position he has held since In 2003, he was also appointed Head of the Institute of Clinical Neurosciences. Dr Fernández gained his licensure in medicine and surgery from the Faculty of Medicine, Complutense University of Madrid, Spain. He completed his residency in neurology and internal medicine at the Hospital Clínico San Carlos in Madrid, before being awarded a PhD from the Faculty of Medicine of the University of Malaga in Subsequently, Dr Fernández was appointed Head Neurologist in the Department of Neurology at the Hospital Regional Universitario Carlos Haya. Malaga. He has been President of the Medical Advisory Committee of the Fundación Española de Esclerosis Múltiple (FEDEM) since 1996, and was appointed President of the Andalusian Neurology Society in November Dr Fernández has authored over 200 published papers and book chapters, and serves as a reviewer for several national and international neurological journals. 12

15 Mark S. Freedman Speaker: Session III Multiple Sclerosis Research Unit The Ottawa Hospital Ottawa, Canada Mark S. Freedman is Professor of Medicine (Neurology) at the University of Ottawa and Director of the Multiple Sclerosis Research Unit at the Ottawa Hospital, General Campus. He received his medical degree from the University of Toronto and received postgraduate neurology specialist training at Queen Square in London, UK, the University of Toronto, and the Montreal Neurological Institute. Dr Freedman is a Fellow of the Royal College of Physicians and Surgeons of Canada (RCPSC), the American Academy of Neurology (FAAN), and the College of Specialists of Quebec (CSPQ). For more than 25 years, Dr Freedman has been devoted to translational research, with the main goals of understanding the immunopathogenesis of, and developing successful treatments for, MS. He has been the principal investigator on numerous clinical trials of new agents in MS, as well as been active on steering committees that help design new clinical trials. Dr Freedman has published over 100 articles, book chapters and abstracts, and has given hundreds of invited lectures and presentations, on both a national and an international level. Gavin Giovannoni Speaker: Session III / Discussant: Session IV Department of Neurology The Royal London Hospital Whitechapel, London, UK Gavin Giovannoni was appointed to the Chair of Neurology, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London and the Department of Neurology, Barts and The London NHS Trust in November In September 2008 he took over as the Neuroscience and Trauma Centre Lead in the Blizard Institute of Cell and Molecular Science. Professor Giovannoni did his undergraduate medical training at the University of the Witwatersrand, South Africa, where he graduated cum laude in 1987, winning the prizes for best graduate in medicine and surgery. He moved to the Institute of Neurology, University College London, Queen Square, London in 1993, after completing his specialist training in neurology in South Africa. After 3 years as a clinical research fellow, under Professor Ed Thompson, and then 2 years as the Scarfe Lecturer, working for Professor W. Ian McDonald, he was awarded a PhD in immunology from the University of London in He was appointed as a Clinical Senior Lecturer, Royal Free and University College Medical School, in 1998 and moved back to the Institute of Neurology, Queen Square in He was promoted to Reader in Neuroimmunology in His clinical interests are MS and other inflammatory disorders of the CNS. He is particularly interested in clinical issues related to optimizing MS diseasemodifying therapies. Professor Giovannoni s current research is focused on Epstein Barr virus as a possible cause of MS, defining the multiple sclerosis endophenotype, MS-related neurodegeneration, biomarker discovery, clinical outcomes and immune tolerance strategies. His team focuses on translational research and therefore have an active clinical trial programme. 13

16 Biographies Ralf Gold Speaker: Session I University of Bochum Bochum, Germany Ralf Gold headed the Institute for Multiple Sclerosis Research, University of Goettingen and Gemeinnützige Hertie-Stiftung, until becoming Chair of the Department of Neurology, University of Bochum at St. Josef-Spital, in August Here, the annual number of patients with MS comes to more than 1200 outpatients and 800 inpatients. His department performs independent laboratory testing for neutralizing autoantibodies against natalizumab in Germany and some other countries. Dr Gold s main scientific interest is in translational therapies for MS, experimental immunotherapies in animal models of MS and Guillain Barré syndrome, and neurobiological disease modulators. He serves as the leading clinical physician and as Principal Investigator in a number of controlled therapeutic trials in MS, and is involved in several scientific research programmes and advisory boards. Currently he is a member of the ECTRIMS Executive Committee and the German Neurological Society board, and is panel leader of the EFNS Demyelinating Diseases Section. Recently he coordinated the update of the German Neurological Society MS guidelines. Dr Gold is a member of several societies, including the German Society for Neurology, the American Academy of Neurology and the Advisory Board of the German MS Society. He has received several scientific awards for his experimental and clinical studies. He also contributes to several editorial boards. From his scientific work, more than 200 original publications and 80 review articles have been published. Bernd C. Kieseier Speaker: Session I Department of Neurology Heinrich-Heine University Düsseldorf, Germany Bernd C. Kieseier received his undergraduate training at the Johannes-Gutenberg Univer-sity of Mainz, Germany and the Medical School of West Virginia University, Morgantown, USA. After graduation as MD in 1994 he worked as an immunology fellow at the New York State Institute for Basic Research in New York, USA, followed by stays at the Lerner Re-search Institute, Cleveland Clinic, Ohio. He received training in Neurology at the Univer-sity of Würzburg, Germany and the University of Graz, Austria, where he became Professor of Neurology in Since December 2001 he is affiliated to the Department of Neurology at the Heinrich-Heine- University Düsseldorf, where he is Vice-Chair of the Department and Head of the MS Outpatient Clinic. His major clinical and research interests beyond general neurology are in the field of ex-perimental and clinical neuroimmunology with a focus on multiple sclerosis and immune-mediated neuropathies. He has authored or co-authored more than 200 articles in peer reviewed journals, written more than 40 book chapters and edited 3 books on neurology, neuroimmunology, peripheral nerve diseases and multiple sclerosis. Professor Kieseier participated in various clinical trials on MS as principle investigator, and is member of the medical advisory board of the German MS Society and member of the German Competence Network Multiple Sclerosis (KKNMS). 14

17 Dawn Langdon Speaker: Session IV / Presenter: Session IV Department of Psychology Royal Holloway University of London London, UK Dawn Langdon completed her training as a Clinical Psychologist at Oxford University, Oxford, and the Institute of Psychiatry, London. She worked as a Clinical Neuropsychologist at the National Hospital, Queen Square, London, obtaining a PhD on reasoning in organic brain syndromes. She is a registered Neuropsychologist and a Health Psychologist. Dr Langdon is now a Professor of Neuropsychology at Royal Holloway, University of London and neuropsychology lead on a number of multinational trials. Her research work centres on psychological aspects of MS and current projects include the efficacy of medication in protecting cognition, cognitive rehabilitation, cognitive profiles in clinically isolated syndrome and early MS, and cognition in the later stages of MS, including its relation to early disease status. Dr Langdon is a frequent contributor to international scientific meetings and committees and is a Trustee of the UK MS Trust, with whom she has authored the MS cognition website She is co-chair of the BICAMS project. Lucia Moiola Discussant: Session II Department of Neurology Institute of Experimental Neurology Vita-Salute San Raffaele University, Milan, Italy Lucia Moiola received a degree in medicine in 1989 and a neurological certification in 1996, both from Milan University. She obtained her PhD in 1996 from the University of Milan. In 1989, she joined the Department of Neurology at the Scientific Institute San Raffaele, Milan University, as a student, and then in 1999 as a Clinical Assistant. Dr Moiola is currently the Outpatient Area Coordinator at the Day Hospital of the Neurological Department, Scientific Institute San Raffaele, Milan. Dr Moiola s research interests are principally within inflammatory-demyelinating pathologies of the CNS, in particular MS: immunology, epidemiology, genetics, diagnosis and treatment. She has wide experience in clinical trials of new agents for MS. She is a member of the Italian Paediatric MS Study Group. Furthermore, she has experiences in NMO spectrum disorder : immunology, epidemiology, diagnosis and treatment for Devic disease and limited forms of neuromyelitis optica. She is also interested in primary and secondary CNS vasculitis, and in particular primary angiitis of the CNS. Dr Moiola has authored and co-authored about 100 papers in peer-reviewed scientific journals. 15

18 Biographies Jorge Oksenberg Speaker: Session III Department of Neurology University of California at San Francisco (UCSF) San Francisco, USA Jorge Oksenberg holds the G. Zimmermann Endowed Chair in Neurology and is Professor of Neurology at the University of California in San Francisco (UCSF). Dr. Oksenberg received his PhD in immunology in 1987 from the Hebrew University of Jerusalem, Israel, and joined the UCSF faculty in 1993 following post-doctoral training at Stanford University, California. Dr Oksenberg is a leading investigator in the multicentre Multiple Sclerosis Genetics Group and the International Multiple Sclerosis Genetics Consortium. Dr. Oksenberg has published over 200 peer-reviewed articles and scholarly reviews, and serves as associate editor for the Annals of Neurology. Peter Rieckmann Presenter: Session II / Speaker: Session IV / Discussant: Session IV Bamberg Hospital and University of Erlangen Bamberg, Germany Peter Rieckmann received his medical degree from the University of Göttingen, Germany, in After a postdoctoral fellowship in molecular immunology at the NIH, Bethesda, USA, he completed his training in Neurology at the National Institute for Nervous Disease, London, UK, and the University of Göttingen. Professor Rieckmann received Board certification in Neurology in 1995; his academic and clinical positions have included Senior (staff) Neurologist and Professor for Neurology, Department of Neurology, as well as Head of the Clinical Research Group for Multiple Sclerosis and Neuroimmunology, at the Julius-Maximilians University of Würzburg, Germany. He holds several position as visiting professor across the globe. In 2007 Professor Rieckmann became the MS Society of Canada Research Chair and Director of the MS Program at the University of British Columbia and Vancouver Hospital, Canada. Under his leadership the Vancouver programme was awarded Western-Pacific Research and Training Center by the MS Society of Canada. He is founding member of the EndMS campaign in Canada. Professor Rieckmann s major research interests are disease-modifying factors and regeneration in MS, as well as functional aspects of the blood brain barrier in neuroimmunological diseases. Professor Rieckmann s clinical goals include enhancing awareness and education about MS, developing effective and properly resourced services for MS outpatient care, and providing more customized treatments for patients. As a clinician scientist he has been actively involved in different efforts to transfer bench results to clinical developments, and serves on steering committees of various international multicentre MS trials (Phase II and III). In September 2009 he started a new position as Director of the Neurological Clinic at the Academic Hospital in Bamberg, and Professor of Neurology at the University of Erlangen, Germany, but will continue his Research Chair at UBC, Vancouver. Professor Rieckmann is a Fellow of the Royal College of Physicians and Surgeons, Canada, and has received numerous awards and research grants. He has over 200 papers to his credit in peer-reviewed medical journals. 16

19 Alex Rovira Speaker: Session III Multiple Sclerosis Center of Catalonia Unit of Clinical Neuroimmunology Vall d Hebron University Hospital, Barcelona, Spain Alex Rovira is a full-time neuroradiologist who received his medical degree in 1983 from the Autonomos University of Barcelona. After formal training in radiology at Vall d Hebron University Hospital, Barcelona, he undertook a visiting fellowship at Shands Hospital, Gainesville, University of Florida, in In 1990 he became staff neuroradiologist at the Vall d Hebron University Hospital, and since 1991, is Director of the Magnetic Resonance Unit of the Department of Radiology. In 2007 Dr Rovira obtained the European Qualification in Neuroradiology issued by the European Board of Neuroradiology. Jaume Sastre-Garriga Speaker: Session IV / Discussant: Session IV Multiple Sclerosis Center of Catalonia Unit of Clinical Neuroimmunology Vall d Hebron University Hospital, Barcelona, Spain Jaume Sastre-Garriga serves as a neurologist at the Unitat de Neuroimmunologia Clínica (UNIC), MS Centre of Catalonia (CEM- Cat), Hospital Vall d Hebron (Barcelona). He is coauthor of 66 peer-reviewed papers and 11 book chapters or monographs; he has coauthored more than 40 oral presentations and more than 70 poster presentations at national and international conferences. He serves as a reviewer for Multiple Sclerosis, Neuroimage, Human Brain Mapping, Archives of Neurology and Neurología, and for the Spanish granting body Fondo de Investigaciones Sanitarias (FIS), the Italian MS Society (FISM), the Catholic University of Leuven (KUL) and the Spanish Neurological Society (SEN). He has served as faculty or organizer for more than 100 lectures, both to health professionals and organizations for patients and their relatives. Dr Sastre-Garriga s main interests are new magnetic resonance imaging techniques (functional MRI and volumetry) and neurorehabilitation, with a special focus on the primary progressive forms of MS. 17

20 Biographies Alan J. Thompson Speaker: Session II Department of Brain Repair and Rehabilitation, Institute of Neurology University College London, National Hospital for Neurology and Neurosurgery Queen Square, London, UK Alan Thompson is Dean of the Faculty of Brain Sciences at University College London, and Programme Director for the Neurological Disorders theme of UCL Partners (Academic Health Science Centre). He is Garfield Weston Professor of Clinical Neurology and Neurorehabilitation at the UCL Institute of Neurology, and a consultant neurologist at the National Hospital for Neurology and Neurosurgery, Queen Square. His main area of expertise is demyelinating disease, particularly the diagnosis, evaluation and management of MS. His research focuses on the pathological mechanisms that underpin neurological disability and recovery, using structural and functional imaging, and developing scientifically sound outcome measures that incorporate the patient s perspective. He has published extensively in these areas. Through his role with UCL Partners, he has jointly led innovation in the treatment pathways for stroke and brain cancer. Professor Thompson is a Senior Investigator for the National Institute for Health Research, Editor-in-Chief for Multiple Sclerosis Journal, chairman of the International Medical and Scientific Board of the Multiple Sclerosis International Federation (MSIF), and a Guarantor of Brain. Professor Thompson received his undergraduate and postgraduate degrees from Trinity College Dublin, Ireland, and has been awarded an honorary doctorate by Hasselt University, Belgium. Mar Tintorè Speaker: Session II Multiple Sclerosis Center of Catalonia Unit of Clinical Neuroimmunology Vall d Hebron University Hospital, Barcelona, Spain Mar Tintorè is co-founder and senior neurologist at the Unitat de Neuroimmunologia Clínica (UNiC), MS Centre of Catalonia (CEM- Cat), Hospital Vall d Hebron, Barcelona, Spain. The unit follows a patient base of over 4000 patients with MS and receives about 600 new cases for investigation, diagnosis and therapy. The unit sees about 120 patients each week, 20 of whom are new referrals. At present, Phase II, III and IV clinical trials are being conducted at UNiC. Dr Tintorè s main line of research at UNiC is based on first presentations of demyelinating events, magnetic resonance, immunological aspects and MS treatment. Dr Tintorè is currently involved in the furthering of the European MAGNIMS research programme, which studies magnetic resonance in clinically isolated syndromes (CIS) and early MS. Dr Tintorè also has an interest in other aspects of MS, such as fatigue and its immunological features, which has gained funding from national research agencies. Dr Tintorè s work on CIS and development to MS has been referenced in the published McDonald diagnostic criteria. Dr Tintorè has authored over 100 publications in national and international peerreviewed journals, and serves as a reviewer for national and international journals and national research support and funding agencies. 18

21 Antonio Uccelli Speaker: Session I MS Clinic and Neuroimmunology Unit Department of Neuroscience, Ophthalmology and Genetics University of Genoa, Genoa, Italy Antonio Uccelli was born in Genoa, Italy, in 1964, where he obtained his medical doctoral degree in He completed his residency in neurology at the University of Genoa in In 1992 he was a post-doctoral fellow in the Laboratory of Neuroimmunology, Department of Neurology, University of California San Francisco (UCSF), directed by Professor S.L. Hauser. In 1993 he obtained a faculty position in the Department of Neurology at the University of Genoa. Since 1995 Professor Uccelli has been the Director of the Neuroimmunology Unit of his Department, focusing his research activities on MS and more recently on adult stem cells. In 2001 he was awarded the Rita Levi Montalcini Award, presented every year to the best Italian researcher in the field of MS. In 2001 he joined the Center of Excellence for Biomedical Research at the University of Genoa, directed by Professor Benatti. In 2008 he became the Director of the Neuroimmunobiology Laboratory of the Advanced Biotechnology Center of Genoa, and in 2009 the Director of the Center for Research and Cure of Multiple Sclerosis of the University of Genoa. Since February 2012 he is the Director of the Residency School of Neurosurgery at the University of Genoa. He is also an Associate Professor of Neurology at the University of Genoa since December Professor Uccelli is co-author of 100 peer-reviewed scientific publications and has been invited to give seminars and keynote lectures at many academic sites and conferences all over the world. Since 1995 he has received numerous scientific grants from national and international agencies. Patrick Vermersch Speaker: Session I Department of Neurology University of Lille Lille, France Patrick Vermersch studied medicine at the University Hospital in Lille, France, where he graduated with a medical thesis concerning the correlations between postural and oculomotor disturbances in Parkinson s disease. He then completed his education in more basic fields, mainly in cellular biology from 1990 to 1994 with a PhD focused on biochemical abnormalities associated with Alzheimer s disease and other neurodegenerative diseases. Professor Vermersch has also conducted research related to the characterisations of post-transcriptional anomalies of Tau proteins. His research interests then turned to MS. Professor Vermersch is Head of one of the Departments of Neurology, University of Lille, France, which deals with MS and other neuro-inflammatory diseases. The principal scientific interests of the department are neuroimmunology and markers of disease evolution. Professor Vermersch is President of the Scientific Committee of the University Hospital. He was Vice-President of the Regional Scientific Consultative Committee of INSERM (Institut National de la Santé et de la Recherche Medicale) from 1994 to In 2000 he created the first MS network in northern France to improve both care and research in MS. Professor Vermersch s main areas of interest are prognostic markers of MS and neuroimmunology in general. He participates in many clinical trials in MS and as author or co-author, he has published approximately 260 scientific papers. 19

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23 Abstracts

24 L1 - Improving understanding of mechanism of action of immunomodulatory drugs Bernd C. Kieseier Department of Neurology, Heinrich-Heine University, Du sseldorf, Germany The mechanism of action (MOA) of any drug has major implications for its efficacy and safety profile, whatever the therapeutic area. In MS, work to characterize the MOA of the disease modifying drugs (DMD) interferon beta and glatiramer acetate has been ongoing for many years. Evidence is emerging that these drugs have complex, multifactorial mechanisms, involving multiple aspects of the innate and acquired immune system. Natalizumab and fingolimod have more recently become available for the treatment of MS. In contrast to immunomodulatory mechanisms of interferon beta and glatiramer acetate, both of these drugs affect MS pathology by limiting entry of activated immune cells to the central nervous system, although by different mechanisms, which are reflected in each drug s efficacy and safety profile. This presentation will summarize what is known about the MOA of the currently available treatments for MS, as well as the proposed MOAs of DMDs still in development. The adverse event profile of a drug is intimately linked to the MOA and the clinical implications of this for current and new drugs will be discussed. The hope is that in the future a full understanding of the MOA of each available drug may translate to more informed treatment decisions to suit individual patients. References: 1 - Xxx xxxxxxxxxx. Human Reproduction Xxx xxxxxxxxxx et al. 22

25 L2 - Neuroprotection and steps towards neuroregeneration: promising therapeutic targets Ralf Gold University of Bochum, Bochum, Germany In view of the limited efficacy of immunotherapies for MS, especially in the later progressive stages of the disease, there are ongoing attempts to develop neuroprotective drugs that may also have immunomodulatory functions. Amongst them are laquinimod, fumarate (BG12) and fingolimod. Laquinimod is a promising, orally available compound that was successfully evaluated in placebo-controlled Phase II/III studies in relapsing remitting MS (RRMS). Furthermore, analyses in the animal model of experimental autoimmune encephalomyelitis (EAE) demonstrate that laquinimod reduces infiltration of leukocytes into the central nervous system (CNS), induces a Th1 to Th2/3 shift, and has a potential neuroprotective capacity via modulation of brain-derived neurotrophic factor. In particular, modulation of monocytes by laquinimod mediates this neuroprotection, and it has been translated in clinical studies where brain atrophy was clearly diminished in patients exposed to laquinimod for 2 years. Fumaric acid was originally used therapeutically in psoriasis. Several lines of evidence have demonstrated both immunomodulatory and neuroprotective effects of fumaric acid. Animal experiments in the mouse model of the CNS, myelin oligodendrocyte glycoprotein-induced EAE, revealed a clear preservation of myelin and axonal density in EAE plaques. Molecular studies showed that this resulted from an antioxidative effect via induction of the transcription factor Nrf-2. A Phase II clinical trial of dimethylfumarate (BG12) in patients with RRMS showed a significant reduction in the number of gadolinium-enhancing lesions after 24 weeks, and this has recently been complemented by two Phase III, trials where a 50% reduction in relapse rate was observed compared with the placebo group. With fingolimod, the pluripotent action on S1P receptors not only mediates the sequestration of lymphocytes into peripheral immune organs, but also has the potential to stimulate oligodendrocytes for remeylination. In addition to these drugs, novel approaches to enhance neurorepair will be discussed. 23

26 L3 - Resetting the immune system: stem cell transplantation Antonio Uccelli MS Clinic and Neuroimmunology Unit, Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, Italy Recent advances in our understanding of stem cell biology, such as the availability of innovative techniques, which allow stem cells to be obtained on a large scale, and the increasing pressure from patients for tissue repair strategies, have launched stem cell treatments as one of the most exciting and difficult challenges in the MS field. Here, an overview of the current status of stem cell research in MS is provided, focusing on confirmed advances, reasonable hopes and unrealistic myths. Results obtained from small clinical studies of transplantation of autologous hematopoietic stem cells have demonstrated that this procedure is feasible and possibly effective in severe forms of MS, but tackles only inflammation without affecting tissue regeneration. Results from preclinical studies with other adult stem cells such as bone marrow derived mesenchymal stem cells have shown that they may be a powerful tool to regulate pathogenic immune response and possibly foster tissue repair. However, the possible clinical translation of these results still requires careful evaluation. Therefore, current experimental evidence suggests that the sound clinical exploitation of stem cells for MS may lead to novel strategies aimed at blocking uncontrolled inflammation, resetting the immune system, protecting neurons and promoting remyelination, but not at restoring the chronically deranged neural network responsible for irreversible disability typical of the late phase of MS. 24

27 L4 - Efficacy profiles of MS drugs Giancarlo Comi Department of Neurology, Institute of Experimental Neurology, Vita-Salute San Raffaele University, Milan, Italy For almost 20 years, clinicians have been able to treat MS with disease-modifying drugs (DMDs) with the intention of reducing or arresting the progression of physical disability. Today s neurologists are familiar with the efficacy and safety profiles of the established immunomodulatory DMDs. The arrival of newer drugs on the one hand offers additional therapeutic options, and on the other presents uncertainty regarding optimal treatment algorithms and the longer-term safety of new drugs. This presentation will give an overview of the safety and efficacy profiles of the available DMDs for MS, then discuss how this information allows the design of treatment algorithms that can be tailored to the needs of the individual patient. In MS there are two approaches to sequential use of DMDs: the escalation approach begins with the use of the established immunomodulators and, in the event of breakthrough disease, steps up to more potent and potentially more dangerous agents; with the induction approach, a more potent drug usually with a higher risk profile is used initially for a limited period, followed by maintenance therapy with an immunomodulator. As more DMDs become available for MS, the potential sequencing becomes increasingly complex and it is important to take into account prognostic factors before determining the most appropriate algorithm for each patient. Furthermore, depending on the mechanisms of action of available drugs, combination regimens may soon be possible. These themes will be discussed in this presentation to clarify how the clinician can use the range of available drugs to create treatment schemes that are optimally effective for each patient, while minimizing risk. 25

28 L5 - Monitoring drug safety in clinical practice Patrick Vermersch Department of Neurology, University of Lille, Lille, France The past two decades have seen tremendous expansion in therapeutic options for patients with relapsing forms of MS. While the growing armamentarium of therapies provides physicians and patients an array of available options, it also brings in its wake the challenging responsibility of choosing the optimal therapy for an individual patient. Interferon beta and glatiramer acetate are generally considered the first-line drugs in relapsing MS and have well-characterized safety profiles. However, these drugs are not optimally effective in all patients. Potentially more potent drugs are also available, but the benefit of heightened efficacy must be weighed carefully against increased risks. Several strategies have been proposed with the aim of minimizing these risks. To improve adherence to therapy, it is important to educate patients regarding adverse events (AEs) and to manage AEs proactively. The greatest risk for patients receiving mitoxantrone is cardiotoxicity; thus, the cumulative dose is limited. A systematic cardiac evaluation including echography or scintigraphy is important before mitoxantrone treatment and 6-monthly or annually for at least 5 years after treatment. Additionally, regular blood tests are recommended to detect sustained lymphopenia or neutropenia. Allergic reactions can occur with natalizumab, and there is a risk of progressive multifocal leukoencephalopathy (PML). Clinical vigilance is crucial to detect early signs of susceptibility. Natalizumab treatment duration and prior use of immunosuppressive therapies are established risk factors for PML in patients who test positive for the John Cunningham Virus (JCV). Recommendations for the clinical management of patients with MS and use of natalizumab are provided based on the presence of these three risk factors. Expertise in magnetic resonance imaging (MRI) monitoring techniques is fundamental in following patients at risk of PML. Different protocols for MRI monitoring are recommended depending on the risk of PML. Very recently the European Medicines Agency gave new advice to healthcare professionals to reduce the risk of adverse effects on the heart associated with the use of fingolimod. The Agency s Committee for Medicinal Products for Human Use recommends that all patients starting treatment with fingolimod should have their heart activity monitored before receiving the first dose of the medicine and continuously for at least 6 hours after. Monitoring should be extended for at least 2 hours in patients whose heart rate is lowest 6 hours after receiving the first dose of fingolimod. In patients who develop clinically significant heart problems, such as bradycardia or atrioventricular block, monitoring should continue at least overnight and until the problems have been resolved. Fingolimod-associated macular oedema has been noted in fingolimod trials but appears to be dose-dependent and very rare with the approved 0.5 mg dose. In patients with diabetes or history of uveitis, an ophtalmologic examination is required before treatment onset, after 3 months and thereafter if necessary. The authorities have also given various other recommendations for fingolimod treatment, such as prohibited drug combinations, vaccination, contraception and blood tests specifically for lymphocyte counts and liver functions every 3 months for the first year of treatment and periodically thereafter. Safety needs to be considered a priority. Considering these risks and the possible approval of new drugs in the near future, each with specific safety issues, it is vital that experts promote educational therapeutic programmes for neurologists, other physicians potentially involved, nurses and patients. References: 1 - Xxx xxxxxxxxxx. Human Reproduction Xxx xxxxxxxxxx et al. 26

29 L6 - McDonald criteria 2010: making the diagnosis easier Alan J. Thompson Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery Queen Square, London, UK The diagnosis of MS remains firmly based on clinical evaluation and the essential need to provide evidence for dissemination in time and space and, importantly, to exclude other neurological conditions that could cause similar symptoms. While investigations are important to exclude other conditions, the interpretation of their results will only be as good as the clinical premise on which they are based. The evolution of diagnostic criteria since Poser in 1983 has focused on improved definition and greater precision. The introduction of magnetic resonance imaging (MRI) has had a major impact on both the timing and accuracy of diagnosis. The initial McDonald criteria (2000) incorporated MRI for the first time and were very cautious in order to maximise specificity. They incorporated the Barkhof criteria to determine dissemination in space and time, but these criteria are complex, and not easily applied. Criteria for primary progressive MS (PPMS) were distinct and had even less evidence base. The subsequent revisions of the McDonald criteria in 2005 and 2010 simplified the MRI criteria for dissemination in both time and space, based on sound studies, reduced the emphasis on cerebrospinal fluid findings in PPMS and drew more closely together the criteria for the relapsing and progressive forms of the condition. In addition, the recent 2010 version, addresses, for the first time, the complexities of neuromyelitis optica and the spectrum of related disorders, in addition to the topical issue of paediatric MS. 27