Ectrims 2013 symposium giovannoni


Published on

Published in: Health & Medicine, Technology
1 Like
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Ectrims 2013 symposium giovannoni

  1. 1. The Challenges of Disease Management in MS: Navigating the Changing Landscape October 4, 2013 ECTRIMS Annual Meeting A Genzyme-sponsored Symposium RESTRICTED USE – SEE TRAINING MEMO 2011 DO NOT COPY OR DISTRIBUTE Genzyme Corporation 1
  2. 2. Agenda Time Title Presenter 6:00 pm Welcome and Introduction Prof. Per Soelberg Sørensen (Chair) Copenhagen University Hospital, Copenhagen, Denmark 6:05 pm Prof. Gavin Giovannoni Highlights from the Changing Landscape of MS • Alemtuzumab for Treatment of Relapsing-Remitting MS Prof. Tjalf Ziemssen Center of Clinical Neuroscience University of Technology, Dresden, Germany • Teriflunomide for Treatment of Patients with MS 6:20 pm Evolving Considerations for Patient Management & Treatment Selection Patricia K Coyle, MD Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London – United Kingdom MS Comprehensive Care Center, Stony Brook University, New York 6:50 pm Questions and Answers 2
  3. 3. Evolving Considerations for Patient Management and Treatment Selection Professor Gavin Giovannoni Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK
  4. 4. Disclosures Professor Giovannoni has received personal compensation for participating on Advisory Boards in relation to clinical trial design, trial steering committees and data and safety monitoring committees from: Abbvie; Almirall; Bayer-Schering Healthcare; Biogen-Idec; Canbex; Eisai; Elan; Fiveprime; Genzyme, a Sanofi Company; Genentech; GSK; GW Pharma; Ironwood; Merck-Serono; Novartis; Pfizer; Roche; SanofiAventis; Synthon BV; Teva; UCB Pharma; and Vertex Pharmaceuticals. Please note that the contents of Professor Giovannoni’s slides have been checked by Genzyme to make sure they are compliant with legal requirements of the Danish authorities and that Professor Giovannoni has agreed to the necessary changes being made. Professor Giovannoni would like to acknowledge and thank Yasamin Mir-Shekari, Evidence Scientific, for editorial assistance with preparing these slides. 4
  5. 5. Why Treat Early in MS?  Reduce axonal loss Pathology Trapp et al, 1998  Slow brain volume loss Imaging Losseff et al,1996  Delay or prevent disability Clinical Confavreaux, Compston, 2005 5
  6. 6. Axonal and Brain Volume Loss Starts Early in MS Disease Severity Subclinical disease First clinical event RRMS RRMS SPMS SPMS Inflammation Axonal loss Brain volume Time (Years) MRI Events  Subclinical inflammation, demyelination, and neurodegeneration may be present for months, or even years, before a patient experiences clinical symptoms1 MRI=magnetic resonance imaging; RRMS=relapsing-remitting MS; SPMS=secondary progressive MS 1. Stüve O et al. Drugs 2008;68:73-83; Image adapted from Compston A, Coles AJ. Lancet 2008;372:1502-17. 6
  7. 7. The Burden of MS Increases with Disability Progression Essentially restricted to bed, chair, or wheelchair (Perfect health) 1.0 Austria Belgium Germany Italy The Netherlands Spain Sweden Switzerland UK UKa UKa Utility Score 0.8 0.6 0.4 0.2 (Death) 0 0 1 2 3 4 5 6 6.5 7 8 9 –0.2 Expanded Disability Status Scale –0.4  As disability increases in MS patients, health status deteriorates1 – At least two-thirds of patients with RRMS are unemployed due to the disease2 – Approximately 21% of patients with MS for less than 5 years are unemployed3 – Social relationships are impacted by multiple interrelated factors related to physical disability and psychological status4 – Reduced ability to work, pursue leisure activities, and carry on usual life roles due to MS results in diminished quality of life5 a Utility score <0 indicates that patients felt their health state was worse than death. 1. Orme M et al. Value Health 2007;10:54-60; 2. Morales-Gonzales. Mult Scler 2004;10:47-54; 3. Zwibel HL, Smrtka J. Am J Managed Care 2011;17:S139-S45; 4. Gilchrist AC, Creed FH. J Psychosomatic Res 1994;38:193-201. Image adapted from Naci et al. J Med Econ 2010;13:78-89. 7
  8. 8. Question: What Prognostic Group Does the Patient Fall Into? Good Prognosis: Poor Prognosis:  Younger age at onset1,2  Older age of onset1,2  Female sex1-3  Male sex1-3  Optic neuritis4  “Multifocal” onset4  Isolated sensory symptoms4  Efferent systems affected (motor, cerebellar, bladder)4  Complete recovery from first attack5  Long interval to second relapse4  No disability after 5 years4  Normal MRI / low lesion load4  CSF negative for oligoclonal bands2,6  Incomplete recovery from first attack5  High relapse rate in the first 2–5 years4  Substantial disability after 5 years4  Abnormal MRI with large lesion load4  CSF positive for oligoclonal bands2,6 CSF=cerebrospinal fluid 1. Scalfari A et al. J Neurol Neurosurg Pschiatry 2013;00:1-9; 2. Fernandez O. J Neurol Sci 2013;331:10-3; 3. Damasceno A et al. J Neurol Sci 2013;324:29-33; 4. Miller D et al. Lancet Neurol 2005:4;281-8; 5. Confavreux C et al. Brain 2003;126:770-82; 6. Villar LM et al. J Clin Invest 2005;115:187-94. 8
  9. 9. Question: What Prognostic Group Does the Patient Fall Into? Favorable (inactive) Indeterminate (active) Poor (active) Time Aim of treatment 9
  10. 10. Question: Does the Patient Have Active MS? 1 Clinical vs. 2 MRI 3 Biomarkers 10
  11. 11. The Traditional Treatment Paradigm in MS: The Treatment Ladder E Very high efficacy High efficacy Moderate efficacy A J D K X Y B C  Heterogeneity of disease course across different patients and over time can affect treatment response1-3 – While some patients will benefit from modest efficacy therapies, others will not1  Given that early inflammatory events predict long-term disability,4 early, appropriate intervention is critical 1. Rio J et al. Ann Neurol 2006;59:344-52; 2. Miller A et al. J Neurol Sci 2008;274:68-75; 3. Rudick RA et al. Lancet Neurol 2009;545-59. 4. Coyle PK, Hartung H-P. Mult Scler 2002;8:2-9; Figure adapted from Rio J et al. Curr Opin Neurol 2011, 24:230-7. 11
  12. 12. Evolving Paradigm: Individualized Treatment Based on Projected Disease Course Define the individual MS patient profile Discuss therapy options with patient/ Choose therapy no yes MS prognosis Patient preferences Treatment history Potential to remain adherent Therapy Choice: • Therapy choice tailored to individual patient profile, including MS prognosis and consideration of the context of MS disease progression when evaluating risk of treatment Ongoing Assessment: Ongoing assessment Stable on treatment? Gd=gadolinium; NAbs=neutralizing antibodies The Individual MS Patient: • • • • • Clinical – Relapse – Disability progression • MRI – T2 lesions – T1 Gd-enhancing lesions • Biomarkers of reduced drug activity and/or safety – NAbs • Tolerability • Safety event • Adherence 12
  13. 13. Case Study
  14. 14. Case: Woman with RRMS  38 years old  Optic neuritis at age 33 – full recovery; turned down the option of an MRI  Sensory spinal cord syndrome at age 35 – MRI compatible with MS (>9 T2 lesions) – No lumbar puncture – Full recovery; except for mild intermittent symptoms when she exercises  First-line injectable for 3 years (good adherence)  Relapse with a mild left sensory loss  Referred for a second opinion  Switched to alternative injectable with mild persistent side-effects 14
  15. 15. What Prognostic Group Does the Patient Fall Into? Good Prognosis:  Young   Female sex   Optic neuritis   Isolated sensory symptoms  Complete recovery from attack  Indeterminate  Long interval to second relapse   No disability after 5 years   Normal MRI / low lesion load   CSF negative for oligoclonal bands 15
  16. 16. Case: Woman with RRMS  2 years later (40 years old)  Forced to retire due to cognitive impairment and severe fatigue  Developed depression and anxiety  Neutralizing antibodies negative  In her spare time, she becomes an expert patient – Widely read and became internet-savvy – Requests an MRI 16
  17. 17. 17
  18. 18. Does the Patient Have Active MS? 1 NO Clinical vs. 2 YES MRI 3 NO Biomarkers 18
  19. 19. Case: Woman with RRMS  40 years old  Hidden symptoms (cognitive impairment, fatigue, depression and anxiety)  Subclinical activity (new T2 and Gd-enhancing lesions) Q1: Should she be offered escalation therapy? Q2: What would be the outcome had she been offered a highly effective therapy from the outset? 19
  20. 20. The Traditional Treatment Paradigm in MS: The Treatment Ladder Moderate efficacy High efficacy Very high efficacy  E A  D J K X Y B C 5 years 20
  21. 21. Conclusions  MS is a serious neurological disease – Disability, unemployment, negative impact on social relationships, diminished QoL, etc.  Traditional treatment approaches based on trial and error may lead to suboptimal treatment outcomes and continued disease progression in MS  Era of individualized profiling – Prognosis, risk, treatment and monitoring  Evolving treatment paradigm – Individualizing treatment to intervene early and appropriately, to impact long-term disability – Individualized treatment should include treatment adherence considerations; oral therapies may be of benefit in this regard – Early treatment with high/very high efficacy therapy should be considered in appropriate patients who are aware of and willing to accept the associated risks – Monitoring treatment for early signs of suboptimal response before overt clinical decline – New treatment paradigm of treat-to-target of no evidence of disease activity (NEDA) 21