Clinical implications: the potential               of tailored MS treatment                                               ...
Disclosures • This is presentation is part of a Genzyme sponsored symprosium • Research support received from: Bayer-Scher...
Restless legs                                                                                                            S...
Theoretical model: treat early and aggressively and you prevent disability                                                ...
Who discusses mortality with their patients?
Restless legs                                                                                                            S...
Survival in MSers is shortened by 8 to 12 years                                              Survival Probability of Norwe...
The survival disadvantage in MS is                   greater than in other chronic diseases       Standardized Mortality R...
21-year long-term follow-up of IFNb-1b study                                                                  time from st...
Who discusses employment with their patients?
Restless legs                                                                                                            S...
Unemployment                                     Probability of Remaining in Active Employment After Onset of MS          ...
Who discusses relationships with their patients?
Restless legs                                                                                                            S...
Divorce and separation                                 Crude probability of remaining in a relationship after onset of MS*...
Who discusses QoL with their patients?
The effect of MS on Quality of Life                                                                                1†     ...
Who of you routinely measures bloodvitamin D levels in people with MS?
Restless legs                                                                                                            S...
Fracture risk in multiple sclerosis                               Dobson et al. Submitted 2012.
Osteoporosis in multiple sclerosis                             Dobson et al. Submitted 2012.
Treatment Strategy
Despite DMT, disease often continues to progress                                                                          ...
Who monitors prognostic factors of a  treatment response to DMTs?
Restless legs                                                                                                            S...
Breakthrough disease after treatment initiation     Patients with breakthrough disease can be identified with     • Clinic...
Relapse on IFNβ therapy increases risk of                     sustained disability progression       •     Risk is not muc...
Strongest predictor of disability progression on             IFNβ therapy is progression itself      Disease Activity Duri...
MRI to monitor treatment response to                         IFNβ: a systematic review                                    ...
MRI to monitor treatment response to                         IFNβ: a systematic review                                    ...
Clinical importance of neutralising antibodies against IFN-beta on relapses                                               ...
Mean change in EDSS                      Malluci et al. Neurology 2004.
Predictors of long-term clinical response to interferon     beta therapy in relapsing multiple sclerosis                  ...
How to improve adherence to DMTs?
Systematic review of DMTs: treatment discontinuation by   study type                                                      ...
Impact of IFN-β adherence on relapse rate                               1.15                               1.10    Relativ...
The Global Adherence Project (GAP): reasons for non-adherence                      Tired of taking injections             ...
Who engages patients in the decision making   process concerning their treatment?
Moving from compliance to concordance requires a culture change        Compliance model                                   ...
Considerations prior to tailoring individualised treatment                                            Increasingly        ...
The large majority of MS patients want to be more actively involved in decision making                                    ...
Listening to patients’ needs    • Several resources available to help patients      understand treatment options and to ma...
Case scenarios
Case studies: high risk CIS (?)    CIS – high risk/RMS (McDonald    positive under new criteria1)    • 28-year-old woman  ...
Case studies: high risk CIS (?)    CIS – high risk/RMS (McDonald Current (2012) therapy    positive under new criteria1)  ...
Case studies: high risk CIS (?)    CIS – high risk/RMS (McDonald Current (2012) therapy Future (2013) therapy    positive ...
Case studies: Newly diagnosed RRMS    Newly diagnosed RRMS    with extensive risk factors    • 52-year-old      African-Am...
Case studies: Newly diagnosed RRMS    Newly diagnosed RRMS                                         Current (2012) therapy ...
Case studies: Newly diagnosed RRMS    Newly diagnosed RRMS                                         Current (2012) therapy ...
Case studies: RRMS – stable with poor adherence    RRMS – stable with poor    adherence    • 44-year-old woman    • No rel...
Case studies: RRMS – stable with poor adherence    RRMS – stable with poor                                       Current (...
Case studies: RRMS – stable with poor adherence    RRMS – stable with poor                                       Current (...
Case studies: RRMS breakthrough disease    RRMS – breakthrough disease    • 47-year-old woman    • Active lifestyle and ke...
Case studies: RRMS breakthrough disease    RRMS – breakthrough disease     Current (2012) therapy    • 47-year-old woman  ...
Case studies: RRMS breakthrough disease    RRMS – breakthrough disease     Current (2012) therapy                         ...
Conclusions
Summary and conclusions• MS is a bad disease• Prognostic factors• Treatment response markers• Current DMTs have not been a...
Personalised Care
Personalised Care
Personalised Care
Personalised Care
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Personalised Care

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Presentation given at the Russian Neurological Society Meeting, Nizhniy Novogord, 18 June 2012.

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Personalised Care

  1. 1. Clinical implications: the potential of tailored MS treatment Gavin Giovannoni Blizard Institute of Cell and Molecular Science Barts and The London School of Medicine and Dentistry Queen Mary University of London, UKBoth teriflunomide and alemtuzumab are investigational treatments in phase III development. They are not approved by FDA nor EMA for use in MS
  2. 2. Disclosures • This is presentation is part of a Genzyme sponsored symprosium • Research support received from: Bayer-Schering Healthcare, Biogen-Idec, Merck Serono, Merz, Novartis, sanofi-aventis and Teva • Personal compensation received for serving as a grant reviewer, from the Irish Science Foundation • Personal compensation received for participating on advisory boards in relation to clinical trial design, trial steering committees and data and safety monitoring committees for: Bayer-Schering Healthcare, Biogen- Idec, Elan, Fiveprime, Genzyme, GlaxoSmithKline, GW Pharma, Ironwood, Merck Serono, Novartis, Roche, sanofi-aventis, Synthon BV, Teva, UCB Pharma and Vertex Pharmaceuticals • Investigator, CARE-MS I and II studies The views expressed in the following slide sets are those of the individual authors and do not necessarily reflect the views of sanofi-aventis or Genzyme
  3. 3. Restless legs SwallowingA ‘holistic’ approach to MS Balance problems Bowel Falls Sexual dysfunction Tremor Palliative Care Prevention Gait DMTs Rehab Relapses Spasticity Counselling CNS Bladder Clinical trials OTPrimary Care Referral Diagnosis Minimal Moderate Severe End of impairment impairment impairment life care Neurophysiology Studying Pain ITB Radiology Fertility Fatigue Employment ST Depression Physio Insomnia Cognition Suprapubic catheter
  4. 4. Theoretical model: treat early and aggressively and you prevent disability Natural course of disease Later treatmentDisability Later intervention Treatment at diagnosis Intervention at diagnosis Time Disease Onset
  5. 5. Who discusses mortality with their patients?
  6. 6. Restless legs SwallowingA ‘holistic’ approach to MS Balance problems Bowel Falls Sexual dysfunction Tremor Palliative Care Prevention Gait DMTs Rehab Relapses Spasticity Counselling CNS Bladder Clinical trials OTPrimary Care Referral Diagnosis Minimal Moderate Severe End of impairment impairment impairment life care Neurophysiology Studying Pain ITB Radiology Fertility Fatigue Employment ST Depression Physio Insomnia Cognition Suprapubic catheter
  7. 7. Survival in MSers is shortened by 8 to 12 years Survival Probability of Norwegian Patients with RRMS (Hordaland County, Western Norway, 1953–2003) 100 General Population 90 RRMS 95% CI 80 70 Survival (%) 60 50 40 30 20 10 0 0 5 10 15 20 25 30 35 40 45 50 Years After Onset 30 35 40 45 50 55 60 65 70 75 80RRMS=relapsing-remitting MS. Approximate Patient AgeAdapted from Torkildsen NG et al. Mult Scler. 2008;14:1191-1198.
  8. 8. The survival disadvantage in MS is greater than in other chronic diseases Standardized Mortality Ratios in Chronic Diseases Disease SMR (range) Cardiovascular disease1* 1.34 (1.23–1.44) Ischemic stroke2† 1.75(1.38–2.19) Early breast cancer3 2.0 (1.6–2.7) Crohn’s disease4 2.8 MS5 2.8 (2.6–3.1) MS (2–9.9 years after diagnosis)5 2.4 (1.9–2.9) MS (≥10 years after diagnosis)5 3.1 (2.8–3.4) Parkinson’s disease6 3.66 (3.37–3.95) Type 2 diabetes1 4.47 (3.91–5.10)*In patients with type 2 diabetes; †in patients with valvular heart disease in Olmsted County, Minnesota.1. De Marco R et al. Diabetes Care. 1999;22:756-761; 2. Petty DW et al. Mayo Clin Proc. 2005;80:1001-1008; 3. Hooning MJ et al. Int J Radiat OncolBiol Phys. 2006;64:1081-1091; 4. South East England Public Health Observatory, Mortality trends. 2006; 5. Sumelahti ML et al. Mult Scler.2010;16:1437-1442; 6. Hristova DR. Folia Medica. 2009;51:40-45.
  9. 9. 21-year long-term follow-up of IFNb-1b study time from study randomization to deathEarly treatment (3 years) with IFNb-1b was associated with a 47% reduction in the risk of dying over 21 years compared with initial placebo treatment 100% Proportion of patients who are still alive 95% IFNB-1b 250 µg 90% Placebo 85% 80% 75% HR=0.532 (95% CI: 0.314–0.902) 70% 46.8% reduction in hazard ratio Log rank, P=0.0173 65% 0 2 4 6 8 10 12 14 16 18 20 22 At risk: Time (Years) IFNB-1b 250 µg 124 124 121 118 104 Placebo 123 120 117 109 88 Source: Poster Goodin et al. Neurology. 2012 Apr 24;78(17):1315-22.
  10. 10. Who discusses employment with their patients?
  11. 11. Restless legs SwallowingA ‘holistic’ approach to MS Balance problems Bowel Falls Sexual dysfunction Tremor Palliative Care Prevention Gait DMTs Rehab Relapses Spasticity Counselling CNS Bladder Clinical trials OTPrimary Care Referral Diagnosis Minimal Moderate Severe End of impairment impairment impairment life care Neurophysiology Studying Pain ITB Radiology Fertility Fatigue Employment ST Depression Physio Insomnia Cognition Suprapubic catheter
  12. 12. Unemployment Probability of Remaining in Active Employment After Onset of MS Control Persons 1.0 MS Patients 0.8 Probability 0.6 0.4 0.2 0 0 5 10 15 20 25 Time (years)Pfleger et al. Mult Scler. 2010;16:121-126.
  13. 13. Who discusses relationships with their patients?
  14. 14. Restless legs SwallowingA ‘holistic’ approach to MS Balance problems Bowel Falls Sexual dysfunction Tremor Palliative Care Prevention Gait DMTs Rehab Relapses Spasticity Counselling CNS Bladder Clinical trials OTPrimary Care Referral Diagnosis Minimal Moderate Severe End of impairment impairment impairment life care Neurophysiology Studying Pain ITB Radiology Fertility Fatigue Employment ST Depression Physio Insomnia Cognition Suprapubic catheter
  15. 15. Divorce and separation Crude probability of remaining in a relationship after onset of MS* 1.0 Population Controls MSers 0.8 0.6 Probability 0.4 0.2 0 0 5 10 15 20 25 Time to Event or End of Observation (years)*Life table method.Pfleger et al. Mult Scler. 2010; 16:121-126.
  16. 16. Who discusses QoL with their patients?
  17. 17. The effect of MS on Quality of Life 1† EDSS and Utility* Show a Significant Inverse Relationship • MS is one of the most common 0.9 0.8 causes of neurological disability 0.7 0.6 in young adults2 0.5 0.4 • Natural history studies indicateUtilityUtility 0.3 0.2 that it takes a median time of 0.1 0 8, 20, and 30 years to reach the –0.1 irreversible disability levels of –0.2 –0.3 EDSS scores 4.0, 6.0, and –0.4 7.0, respectively3 0.0 1.0 2.0 3.0 4.0 5.0 6.0 6.5 7.0 8.0 9.0 EDSS Status*Utility measures are derived from EQ-5D using the EuroQoL instrument; †error bars depict 95% CIs. Half points on EDSSare not shown on graph axis, except at EDSS score 6.5.EDSS=Expanded Disability Status Scale; EQ-5D=European Quality of Life-5 Dimensions; QoL=quality of life.1. Adapted from Orme M et al. Value In Health. 2007;10:54-60; 2. WHO and MS International Foundation (MSIF).http://apps.who.int/bookorders/anglais/detart1.jsp?sesslan=1&codlan=1 &codcol=15&codcch=747. Accessed March 6, 2012;3. Confavreaux C et al. Brain 2003; 176:770-782. 4. Compston A, Coles A. Lancet. 2008;372:1502-1517.
  18. 18. Who of you routinely measures bloodvitamin D levels in people with MS?
  19. 19. Restless legs SwallowingA ‘holistic’ approach to MS Balance problems Bowel Falls Sexual dysfunction Tremor Palliative Care Prevention Gait DMTs Rehab Relapses Spasticity Counselling CNS Bladder Clinical trials OTPrimary Care Referral Diagnosis Minimal Moderate Severe End of impairment impairment impairment life care Neurophysiology Studying Pain ITB Radiology Fertility Fatigue Employment ST Depression Physio Insomnia Cognition Suprapubic catheter
  20. 20. Fracture risk in multiple sclerosis Dobson et al. Submitted 2012.
  21. 21. Osteoporosis in multiple sclerosis Dobson et al. Submitted 2012.
  22. 22. Treatment Strategy
  23. 23. Despite DMT, disease often continues to progress 1 The natural course of relapsing-remitting MS Secondary Pre-clinical First Relapsing-remitting progressive clinical event Inflammation Axonal loss Disease Severity Brain volume Disability Time (years) MRI Events Despite treatment, approximately one quarter (21–27%) of patients worsened by ≥1 point on the EDSS within 2 years2DMT, disease-modifying therapies; EDSS, Expanded Disability Status Scale.1 Adapted from Compston A et al. Lancet 2008;372:1502–17; 2 O’Connor P et al. Lancet Neurol 2009;8:899–897
  24. 24. Who monitors prognostic factors of a treatment response to DMTs?
  25. 25. Restless legs SwallowingA ‘holistic’ approach to MS Balance problems Bowel Falls Sexual dysfunction Tremor Palliative Care Prevention Gait DMTs Rehab Relapses Spasticity Counselling CNS Bladder Clinical trials OTPrimary Care Referral Diagnosis Minimal Moderate Severe End of impairment impairment impairment life care Neurophysiology Studying Pain ITB Radiology Fertility Fatigue Employment ST Depression Physio Insomnia Cognition Suprapubic catheter
  26. 26. Breakthrough disease after treatment initiation Patients with breakthrough disease can be identified with • Clinical measures – Relapses – EDSS progression • MRI measures – T2 and Gd+ lesions • Biological markers – IFNβ NAbs/lack of MxA gene induction – Natalizumab antibodiesGd+=gadolinium-enhancing; IFNβ=interferon beta; NAbs=neutralizing antibodies; Abs=antibodies; MxA= myxovirus protein A.
  27. 27. Relapse on IFNβ therapy increases risk of sustained disability progression • Risk is not much greater for 2 relapses or more • Sensitivity is only 50% HR of EDSS Increase in Patients with No Relapses, 1 Relapse, and 2 or More Relapses During the First 2 Years of IFN Treatment HR SE P Value 95% CI No relapses (reference=1) 1 One relapse 3.41 1.47 0.005 1.46–7.98 Two or more relapses 4.37 1.74 0.000 1.90–9.57 1.00 No Relapses One Relapse Survival Probability Two or More Relapses EDSS Progression 0.75 0.50 0.25 0 0 20 40 60 80HR=hazard ratio; SE=standard error. Analysis Time (Months)Bosca et al. Mult Scler. 2008;14:636-639.
  28. 28. Strongest predictor of disability progression on IFNβ therapy is progression itself Disease Activity During 2 Years of Treatment and Prediction of Disability Progression* at 6 Years Sensitivity (%) Specificity (%) Group (CI) (CI) A. An increase of at least one EDSS step confirmed at 6 months 85 (64–95) 93 (86–97) B. Occurrence of any relapse 80 (58–92) 51 (41–61) C. Occurrence of two or more relapses 45 (26–66) 81 (72–82) D. A decrease in relapse rate less than 30% compared with 2 years 40 (22–61) 86 (77–91) before therapy E. A decrease in relapse rate less than 50% compared with 2 years 40 (–61) 81 (72–88) before therapy F. No decrease or identical relapse rate compared with 2 years 35 (18–57) 88 (79–93) before therapy G. Definition A or B 90 (70–97) 48 (38–58) H. Definition A or E 85 (64–95) 76 (66–83) I. Definition A and B 75 (53–89) 97 (91–99) J. Definition A and E 40 (22–61) 99 (94–99)*EDSS score ≥6.0 or increase in at least 3 EDSS steps.Río J et al. Ann Neurol. 2006;59:344-352.
  29. 29. MRI to monitor treatment response to IFNβ: a systematic review One New T2 Lesion Odds Ratio Study or Subgroup IV, Random, 95% CI Kinkel 2008 Pozzilli 2005 Prosperini 2009 Sormani 2011 Total (95% CI) 2.69 (0.72, 10.04) 0.01 0.1 1 10 100 Disease Less Likely Disease More Likely Two or More New T2 Lesions Odds Ratio Study or Subgroup IV, Random, 95% CI Kinkel 2008 Prosperini 2009 Total (95% CI) 9.86 (2.33, 41.70) 0.01 0.1 1 10 100 Favors Experimental Favors ControlDobson et al. Submitted 2012.
  30. 30. MRI to monitor treatment response to IFNβ: a systematic review One New Gd+ Lesion Odds Ratio Study or Subgroup IV, Random, 95% CI Kinkel 2008 Pozzilli 2005 Tomassini 2006 Total (95% CI) 3.34 (1.36, 8.22) 0.01 0.1 1 10 100 Disease Less Likely Disease More Likely Two or More New Gd+ Lesions Odds Ratio Study or Subgroup IV, Random, 95% CI Kinkel 2008 Rio 2008 Total (95% CI) 5.46 (2.48, 12.04) 0.01 0.1 1 10 100 Disease Less Likely Disease More LikelyDobson et al. Submitted 2012.
  31. 31. Clinical importance of neutralising antibodies against IFN-beta on relapses Sorensen et al. Lancet 2003; 362: 1184–91.
  32. 32. Mean change in EDSS Malluci et al. Neurology 2004.
  33. 33. Predictors of long-term clinical response to interferon beta therapy in relapsing multiple sclerosis Tomassini et al. J Neurol (2006) 253 : 287–293.
  34. 34. How to improve adherence to DMTs?
  35. 35. Systematic review of DMTs: treatment discontinuation by study type ≤12 months Randomised controlled trial 13–24 months Observational study >24 months 70 70 60 60 Patients discontinuingPatients discontinuing 50 50 treatment (%) treatment (%) 40 40 30 30 20 20 10 10 0 0 IFNβ-1a IFNβ-1a IFNβ-1b GA IFNβ-1a IFNβ-1a IFNβ-1b GA 30 µg IM 44 µg SC 250 µg SC 20 µg SC 30 µg IM 44 µg SC 250 µg SC 20 µg SC q.w. t.i.w. e.o.d. o.d. q.w. t.i.w. e.o.d. o.d. (n=5898) (n=3446) (n=3942) (n=2855) (n=5836) (n=3124) (n=3482) (n=2628) • Treatment discontinuation was • Up to 40% of patients discontinue frequent in both randomised controlled treatment within the first 2 years trials and observational studies Studies included ranged from January 1993 – October 2008DMT, disease-modifying therapy; IFN, interferon; GA, glatiramer acetateGiovannoni & Waubant, MSJ 2012
  36. 36. Impact of IFN-β adherence on relapse rate 1.15 1.10 Relative risk of relapse 1.05 1.00 0.95 4% of patients had MPR >85%, on average 72−76% 0.90 >85% <80% <75% <70% <65% <60% Medication possession ratio (MPR) • Poor adherence to IFN-β* increases relapse rate and healthcare resource utilisationN=1606, 2006−2008; *includes all licensed IFN-β drugs excluding Extavia®IFN, interferon; MPR, medication possession ratioSteinberg SC et al. Clin Drug Investig 2010;30:89–100
  37. 37. The Global Adherence Project (GAP): reasons for non-adherence Tired of taking injections 20 Fatigue 15 Flu-like symptoms 13 N=2648 Pain at injection site 12 32% of patients: at least one Headache 10 injection-related reason Injection anxiety 10 Skin reaction 9 84% of patients: other various Weakness 8 reasons Depression 6 Patients may report more than Did not feel need for injection 4 one reason Forgot to administer 50 Dosing schedule difficult/inconvenient 10 Did not pick up medication 5 Financial reasons 3 Not confident in treatment benefits 2 Injection/tolerability factors Nobody available to administer 2 Patient factors Pregnancy/planned pregnancy 1 Other Other 17 0 10 20 30 40 50 60 Patients (%)Devonshire V et al. Eur J Neurol 2011;18:69–77
  38. 38. Who engages patients in the decision making process concerning their treatment?
  39. 39. Moving from compliance to concordance requires a culture change Compliance model Concordance model Prescriber decides diagnosis Prescriber and patient negotiate and treatment diagnosis and treatment Prescriber’s task is to explain Prescriber and instruct elicits, explains, persuades and accommodates Patient’s task is to Patient explains, considers and comprehend accommodates Successful outcome is Successful outcome is a compliance negotiated agreementFrom Compliance to Concordance. Pharmaceutical Journal 1997;259:860–861
  40. 40. Considerations prior to tailoring individualised treatment Increasingly Treatment complex strategy environment Economic (e.g. induction factors vs escalation) Patient’s own Patient’s prior Individualised adherence to treatment goals treatment monitoring or drug regimen Patient’s own Patient’s own risk/benefit disease profile / Other tolerance characteristics • Many considerations are specific to patients’ needs and need to be layered with 44 physician-specific factors (e.g. treatment strategies) and economic factors
  41. 41. The large majority of MS patients want to be more actively involved in decision making 140 120 Number of patients 100 80 60 40 20 0 Autonomous Active role* Professional Paternalistic as agent • In MS, 79% of patients prefer taking an active role in decision making about their condition*Includes informed choice and shared decision-makingHeesen C et al. J Neurol Sci 2007;259:109–17
  42. 42. Listening to patients’ needs • Several resources available to help patients understand treatment options and to map disease progression on current treatment – One-to-one counselling – Expert patient programmes – Online resources – Smartphone app in development – Education on available therapies and their benefit/risk profiles www.slcmsr.net/publicwww.patientslikeme.com; www.msdecisions.org.uk; www.slcmsr.net/public
  43. 43. Case scenarios
  44. 44. Case studies: high risk CIS (?) CIS – high risk/RMS (McDonald positive under new criteria1) • 28-year-old woman • Married with a young child • Presented with numbness/ muscle weakness and nausea • Several T2 and Gd-enhancing lesions on MRI • Has done considerable web-based research into her condition and understands risks of disease-progressionCIS, clinically isolated syndrome; IFN, interferon; GA, glatiramer acetate;1 Polman CH et al. Ann Neurol 2011;69:292–302†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  45. 45. Case studies: high risk CIS (?) CIS – high risk/RMS (McDonald Current (2012) therapy positive under new criteria1) • 28-year-old woman • Married with a young child • Presented with numbness/ muscle weakness and nausea • Several T2 and Gd-enhancing IFN-β / GA lesions on MRI • Has done considerable Possibly Fingolimod* web-based research into her condition and understands risks of disease-progressionCIS, clinically isolated syndrome; IFN, interferon; GA, glatiramer acetate;* In countries with a 1st-line license1 Polman CH et al. Ann Neurol 2011;69:292–302†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  46. 46. Case studies: high risk CIS (?) CIS – high risk/RMS (McDonald Current (2012) therapy Future (2013) therapy positive under new criteria1) • 28-year-old woman • Married with a young child • Presented with numbness/ muscle weakness and nausea IFN-β / GA • Several T2 and Gd-enhancing Fingolimod lesions on MRI IFN-β / GA BG-12† • Has done considerable Possibly Fingolimod* Teriflunomide† web-based research into her Alemtuzumab† condition and understands risks of disease-progressionCIS, clinically isolated syndrome; IFN, interferon; GA, glatiramer acetate;1 Polman CH et al. Ann Neurol 2011;69:292–302†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  47. 47. Case studies: Newly diagnosed RRMS Newly diagnosed RRMS with extensive risk factors • 52-year-old African-American man • Two attacks within 6 months • High BoD on MRI • EDSS 3.0 • Recovery from attacks has been poor with impact on motor function and some loss of bladder control • JC virus antibody positiveBoD, burden of disease; EDSS, extended disability status scale; GA, glatiramer acetate**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  48. 48. Case studies: Newly diagnosed RRMS Newly diagnosed RRMS Current (2012) therapy with extensive risk factors • 52-year-old African-American man • Two attacks within 6 months High-dose IFN-β / GA • High BoD on MRI Fingolimod** • EDSS 3.0 Natalizumab • Recovery from attacks has been poor with impact on motor function and some loss of bladder control • JC virus antibody positiveBoD, burden of disease; EDSS, extended disability status scale; GA, glatiramer acetate**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  49. 49. Case studies: Newly diagnosed RRMS Newly diagnosed RRMS Current (2012) therapy Future (2013) therapy with extensive risk factors • 52-year-old African-American man • Two attacks within High-dose IFN-β / GA 6 months BG-12† High-dose IFN-β / GA Fingolimod† • High BoD on MRI Fingolimod** Teriflunomide† • EDSS 3.0 Natalizumab Natalizumab† • Recovery from attacks has Alemtuzumab† been poor with impact on motor function and some loss of bladder control • JC virus antibody positiveBoD, burden of disease; EDSS, extended disability status scale; GA, glatiramer acetate**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  50. 50. Case studies: RRMS – stable with poor adherence RRMS – stable with poor adherence • 44-year-old woman • No relapses in past 2 years • No new lesions on MRI, but evidence of increasing lesion volume • Often forgets to administer injections “my disease is stable” • Has experienced injection- site reactions in the pastRRMS, relapsing remitting multiple sclerosis; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  51. 51. Case studies: RRMS – stable with poor adherence RRMS – stable with poor Current (2012) therapy adherence • 44-year-old woman • No relapses in past 2 years • No new lesions on MRI, but evidence of increasing lesion volume IFN-β / GA + MS nurse support • Often forgets to administer Fingolimod** injections “my disease is stable” • Has experienced injection- site reactions in the pastRRMS, relapsing remitting multiple sclerosis; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  52. 52. Case studies: RRMS – stable with poor adherence RRMS – stable with poor Current (2012) therapy Future (2013) therapy adherence • 44-year-old woman • No relapses in past 2 years • No new lesions on MRI, but evidence of increasing lesion IFN-β / GA volume IFN-β / GA + MS BG-12† nurse support Fingolimod† • Often forgets to administer Fingolimod** Teriflunomide† injections “my disease is stable” • Has experienced injection- site reactions in the pastRRMS, relapsing remitting multiple sclerosis; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  53. 53. Case studies: RRMS breakthrough disease RRMS – breakthrough disease • 47-year-old woman • Active lifestyle and keen to retain independence • Failed on one IFNβ • Diagnosed 3 years ago • Several relapses and marked disability progression since diagnosis EDSS = 4.0 • On-going MRI disease activity • Has researched and accepts benefit/ risk profiles of new treatmentsEDSS, extended disability status scale; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  54. 54. Case studies: RRMS breakthrough disease RRMS – breakthrough disease Current (2012) therapy • 47-year-old woman • Active lifestyle and keen to retain independence • Failed on one IFNβ • Diagnosed 3 years ago • Several relapses and marked IFN-β / GA disability progression since Fingolimod* diagnosis EDSS = 4.0 Natalizumab • On-going MRI disease activity • Has researched and accepts benefit/ risk profiles of new treatmentsEDSS, extended disability status scale; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  55. 55. Case studies: RRMS breakthrough disease RRMS – breakthrough disease Current (2012) therapy Future (2013) therapy • 47-year-old woman • Active lifestyle and keen to retain independence • Failed on one IFNβ • Diagnosed 3 years ago IFN-β / GA Natalizumab • Several relapses and marked IFN-β / GA BG-12† disability progression since Fingolimod* Teriflunomide† diagnosis EDSS = 4.0 Natalizumab Fingolimod† • On-going MRI disease activity Alemtuzumab† • Has researched and accepts benefit/ risk profiles of new treatmentsEDSS, extended disability status scale; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
  56. 56. Conclusions
  57. 57. Summary and conclusions• MS is a bad disease• Prognostic factors• Treatment response markers• Current DMTs have not been able to halt disease progression and carry a burden of adherence partly linked to injections • Teriflunomide , Alemtuzumab and other emerging agents help address these needs• As the disease profile and treatment needs of each patient differs, different therapy profiles will be of value • Risk factors and patient views and the addition of new drugs to the treatment armamentarium will increase individualised treatmentBoth teriflunomide and alemtuzumab are investigational treatments in phase III development. They are not approved by FDA nor EMA for use in MS

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