Defining goals and patient expectations

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Defining goals and patient expectations

  1. 1. Defining Goals and Patient Expectations International MS Physician Summit Prague, 22nd-23rd March 2014 Gavin Giovannoni Barts and The London
  2. 2. 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, Bayer-Schering Healthcare, Biogen-Idec, Canbex, Eisai, Elan, Fiveprime, Genzyme, Genentech, GSK, GW Pharma, Ironwood, Merck-Serono, Novartis, Pfizer, Roche, Sanofi-Aventis, Synthon BV, Teva, UCB Pharma and Vertex Pharmaceuticals. Regarding www.ms-res.org survey results in this presentation: please note that no personal identifiers were collected as part of these surveys and that by completing the surveys participants consented for their anonymous data to be analysed and presented by Professor Giovannoni. Professor Giovannoni would like to acknowledge and thank Biogen-Idec, Genzyme and Novartis for making available data slides on natalizumab, alemtuzumab and fingolimod for this presentation. I would like to acknowledge Mark Hughes, from Infusion, who helped me prepare some of my slides. Please note that Professor Giovannoni’s attendance at the 2014 MS Physician Summit, in Prague, was sponsored by Biogen-Idec.
  3. 3. Employment 50% of patients with MS are unemployed 10 years after diagnosis5 Relationships Compared with general population, patients with MS have a higher probability of separating/divorcing and doing so sooner5 Mortality Mortality ratio of MS exceeds CV disease,2,b stroke,3,c and early breast cancer4 Healthcare costs Bulk of cost attributed to services (29%) and long-term sick leave and early retirement (30%)6,d QOL EDSS and utilitya have shown a significant inverse relationship1 MS Is a Disabling Disease MS=multiple sclerosis; QOL=quality of life; EDSS=Expanded Disability Status Scale; CV=cardiovascular; EQ-5D=EQ-5D=EuroQol 5-Dimension questionnaire. 1. Orme M et al. Value Health. 2007;10:54-60. 2. De Marco R et al. Diabetes Care. 1999;22:756-761. 3. Petty DW et al. Mayo Clin Proc. 2005;80:1001-1008. 4. Hooning MJ et a. Int J Radiat Oncol Biol Phys. 2006;64:1081-1091. 5. Pfleger CC et al. Mult Scler. 2010;16:121-126. 6. Berg J et al. Eur J Health Econ. 2006;7 (suppl 2):S75-S85. a. Utility measures derived from EQ-5D b. In patients with type 2 diabetes c. In patients with valvular heart disease in Olmsted County, Minnesota d. MS patients with EDSS ≥6.0 MS has a negative impact on…
  4. 4. Utility (QoL) Scores Make Diseases Comparable 0.45 0.55 0.60 0.75 0.80 0.65 0.70 0.50 0.72 – Mean utility of patients with rheumatoid arthritis at stage 12 0.00 – Worst possible health status 1.00 – Best possible health status 0.55 – Mean utility of patients with MS4 0.48 – Mean utility of severe haemophilia patients with inhibitors5 0.82 – Mean utility of aging patients with osteoporosis, no fracture1 0.58 – Mean utility of patients with Parkinson’s disease3 1. Oleksi A et al. J Bone Miner Res. 2000;15:1384-1392; 2. Holbelt G et al. Arthritis Rheum. 1999;42:347-356; 3. Siderowf A et al. Neurology. 2002;59:103-108; 4. Kobelt G. et al. Eur J Health Econ. 2006;7:S5-S104; 5. Ekert H et al. Haemophilia. 2001;7:279-285.
  5. 5. MS Patients’ Quality of Life Decreases Tremendously, Dependent on EDSS Mean Utility Utilities at Early Disease Utility at Severe Disease Austria 0.55 0.90 0.05 Belgium 0.51 0.85 0.06 Germany 0.62 0.86 0.10 Italy 0.53 0.80 0.06 Netherlands 0.61 0.85 0.05 Spain 0.55 0.87 0.08 Sweden 0.55 0.83 0.05 Switzerland 0.59 0.89 0.10 UK 0.51 0.92 0.18 EQ-5D was used to calculate utilities: Utility is a measure of a person's well-being or preferences for outcomes Mean Utilities and EDSS in Germany1= Perfect health; 0 = Worst health/dead 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 MeanUtility(EQ-5D) EDSS Kobelt G et al. Eur J Health Econ. 2006;7:S5-S104; Kobelt G et al. Eur J Health Econ. 2006;7:S34-S44.
  6. 6. Lessons Learned from Managing RRMS and Two Decades of Disease-Modifying Therapies Disability progression in two phases Treatment changes the disease course In RRMS, gender, age at onset, residual deficit after the first relapse, and relapses during the first 2 years are independent predictors of disability progression only in phase 1 DSSScore Years from clinical onset of MS 6 5 4 3 2 1 0 0 5 10 15 20 25 30 7 Phase 2 Phase 1 Treatment (IFNβ) Impact2 ProbabilityofSPMS 0.05 0.10 0.15 0.20 0.25 Untreated Treated 1 2 3 4 5 6 7 Follow-up Years 0 Natural History1 Propensity score-adjusted survival curves for time from first visit to secondary progression. Cumulative probability represents the estimated proportion of patients reaching the end point 1Data from a retrospective, database review of the Rennes MS database showing the 718 MS patients who had reached both DSS 3 and 6; these were divided into five subgroups defined according to the duration of phase 1 (mean time from MS clinical onset to DSS 3). DSS=disability status scale; RRMS=relapsing remitting MS; SPMS=secondary progressive MS; IFNβ=interferon beta. 1. Leray E et al. Brain 2010;133:1-14. 2. Trojano M et al. Ann Neurol. 2007;61:300-306.
  7. 7. Survival Analysis “Hit hard and early” MS is an autoimmune disease hypothesis 15–20 year experiment What Is Your Treatment Philosophy? Will “Hit Hard and Early” Be Enough
  8. 8. Patient and Disease Profile Shared Decision Making Involves Consideration of Many Factors Shared Treatment Decision Therapy Attributes Patient Preferences Geographic and Economic Factors  Age, gender  Disease activity/disease type  Disability/functional impairment  Treatment history  Comorbidities  Efficacy  Safety  Tolerability  Administration (route/frequency)  Monitoring requirements  Biomarkers (eg, anti-JCV Ab, NAbs)  Socio-demographic profile (lifestyle, work status, family status)  Convenience  Risk tolerance  Likelihood of adherence  Approved usage  Reimbursement/access to drug Shared treatment decision optimally weighs these considerations to arrive at the therapy that best meets the patient’s needs JCV=John Cunningham virus; Ab=antibody; Nab=neutralising Ab.
  9. 9. Managing to the Goals of Therapy Makes for a Stepwise Process Monitoring: Choosing therapy X Y Z Define the Individual’s MS No Treatment failure? Yes • Patient’s preferences? • Your choice? Individual measures: • Evidence of disease activity? • Tolerability/safety? • Adherence? • Drug or inhibitory markers? Monitoring • MS prognosis • Life style and goals • Shared goals for therapy
  10. 10. Defining Shared Goals • Physicians can objectively assess measureable disease outcomes. Targets are – Freedom from disease activity – Long-term stability on EDSS • Patients are interested in therapies that improve their ability to work, parent, socialise, and participate in life. Important outcomes for them are minimising changes in – Fatigue – Cognition – Mobility – Bladder/sphincter control – Sexual function – QoL
  11. 11. Defining Shared Goals • Physicians can objectively assess measureable disease outcomes. Targets are – Freedom from disease activity – Long-term stability on EDSS • Patients are interested in therapies that improve their ability to work, parent, socialise, and participate in life. Important outcomes for them are minimising changes in – Fatigue – Cognition – Mobility – Bladder/sphincter control – Sexual function – QoL “Zero Tolerance” “Aim for Normality”
  12. 12. Escalation to Natalizumab Is More Effective Than Switching Between IFN/GA 72 83 59 5151 67 36 21 0 25 50 75 100 Patients(%) Escalation to natalizumab, n=106 Switch between IFNβ/GA, n=161 Data from a postmarketing, prospective, observational study in 285 RRMS patients for whom treatment with IFNβ or GA therapy failed. After failure of IFNβ or GA therapy, patients were switched to either natalizumab (n=106) or IFNβ/GA (n=161). *At 12 months, the two groups did not differ in proportions of patients free from relapse, disability progression, MRI activity, and combined activity. PS-adj. HR=propensity score-adjusted hazard ratio. Prosperini L et al. Mult Scler. 2012;18:64-71. No EDSS Progression No MRI Activity Disease Activity Free PS-adj. HR: 0.42 P=0.002 PS-adj. HR: 0.56 P=0.006 PS-adj. HR: 0.51 P=0.001 No Relapses PS-adj. HR: 0.38 P=0.003 Over 24 months*
  13. 13. 65.4 87.3 52.9 32.2 46.7 78.9 31.5 13.6 0 25 50 75 100 Relapse-Free SAD-Free (6-month) MRI Activity-Free MS Disease Activity- Free Alemtuzumab 12 mg SC IFNβ-1a 44 μg Escalation to Alemtuzumab Is More Effective Than Switching from IFN/GA to IFNβ-1a 3×/Week OR=odds ratio; SC=subcutaneous; SAD=sustained accumulation of disability. Hartung HP et al. Presented at AAN; March 16–23, 2013; San Diego, CA. P07.093. %ofPatients CARE-MS II: Disease-Free Status over 2 Years OR=3.03 P<0.0001
  14. 14. “Hit Hard and Early”: Natalizumab Stabilises the Disease (Phase 3 and STRATA Studies) 2.36 2.69 2.54 3.13 3.07 3.22 3.24 3.21 3.15 3.17 2.38 2.36 2.39 2.90 2.69 2.72 2.84 2.85 2.79 2.92 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Feeder Study Baseline Feeder Study End Safety Study End† STRATA Baseline STRATA 48 Weeks STRATA 96 Weeks STRATA 144 Weeks STRATA 192 Weeks STRATA 240 Weeks STRATA 288 Weeks 1 Year 2 Years 3 Years 4 Years 5 Years Cessation/ Treatment Gap* Original Placebo Original Natalizumab Original Placebo – Now on Natalizumab MeanEDSSScore n = 380 707 381 707 280 552 385 709 274 569 230 479 205 463 194 427 178 410 150 345 *P<0.0001; †includes data on patients dosed with natalizumab. Rudick R et al. Presented at ECTRIMS; October 2-5, 2013; Copenhagen, Denmark. P593. 6 Years
  15. 15. Real-World Use: At Population Level, Natalizumab Stabilises the Disease Regardless of Disability Level 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 0 6 12 18 24 30 36 42 48 MedianEDSSScore Time (months) Kappos L et al. Presented at ENS; June 9–12, 2012; Prague, Czech Republic. O261. Baseline EDSS Score ≤3.0 (n=1591) Baseline EDSS Score >3.0 (n=1840) Natalizumab should be used according to the SmPC Tysabri Observational Program (TOP)
  16. 16. TOP 5-Year Interim Analysis: EDSS Improvement vs Progression Disability in Overall Population Years* n Mean (SD) EDSS scores 0 4797 3.5 (1.6) 1 2064 3.3 (1.8) 2 1304 3.3 (1.8) 3 744 3.3 (1.8) 4 325 3.3 (1.9) *Years of observation where values for year 0 are those at baseline. EDSS progression was defined as an increase, sustained for 6 months, of ≥0.5 points from a baseline EDSS score ≥6.0, of ≥1.0 point from a baseline EDSS score of ≥1.0 to <6.0, or of ≥1.5 points from a baseline EDSS score of 0. EDSS improvement was evaluated in patients with EDSS scores ≥2.0 at baseline and was defined as a decrease of ≥1.0 point from baseline EDSS score sustained for 6 months. SD=standard deviation; CI=confidence interval. Butzkueven H. et al. J Neurol Neurosurg Psychiatry. 2014; Feb 14. [Epub ahead of print]. Probability of confirmed EDSS improvement was significantly greater than the probability of confirmed worsening (P<0.0001)
  17. 17. Alemtuzumab Also Stabilises Disease over Short Term at Population Level 1. Giovannoni G et al. Presented at AAN; March 16–23, 2013; San Diego, CA. P07.120; 2. Coles AJ et al. Lancet. 2012;380:1829-1839. Mean EDSS: Change from Baseline in CARE MS II MeanEDSSScore Follow-up (months) SC IFNβ-1a 44 µg Alemtuzumab 12 mg 0.24 increase P=0.0064 0.17 decrease P=0.0044 0 3 6 9 12 15 18 21 24 3.0 2.0 1.0 0 4.0
  18. 18. Negative* Anti-JCV antibody status 0.1/1000 Treatment exposure time or prior IS use does not impact the risk estimates as long as the patient remains JCV Ab negative Data beyond 4 years of treatment are limited. *Based on natalizumab exposure and 285 confirmed PML cases as of September 5, 2012. Prior IS data in overall natalizumab-treated patients based on proportion of patients with IS use prior to natalizumab therapy in TYGRIS as of May 2011 and prior IS data in PML patients as of September 5, 2012. The analysis assumes that 55% of natalizumab-treated MS patients were anti-JCV antibody-positive and that all PML patients test positive for anti-JCV antibodies prior to the onset and diagnosis of PML. The estimate of PML incidence in anti-JCV antibody-negative patients is based on the assumption that all patients received at least 1 dose of natalizumab. Assuming that all patients received at least 18 doses of natalizumab, the estimate of PML incidence in anti-JCV antibody-negative patients was generally consistent (0.1/1000; 95% CI 0.00–0.62). In Anti-JCV Ab− Patients, Risk of PML Remains Constant Irrespective of Exposure Time or Prior IS Use IS=immunosuppressant; PML=progressive multifocal leukoencephalopathy. http://multiple-sclerosis-research.blogspot.co.uk/2014/01/clinic-speak-what-is-high-pml-risk.html. Accessed February 21, 2014. Natalizumab should be used according to the SmPC
  19. 19. Anti-JCV Ab Status and Weighing Risk of Disease vs Risks and Benefits of Treatment: AFFIRM D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D Patients with increase in disability 170 Patients with at least 1 relapse 280 Patients with hypersensitivity reactions 40 Patients with no significant harm 680 1000 patients without natalizumab 290 540 0 460 Polman CH et al. N Engl J Med. 2006;354:899-910; Bloomgren G et al. N Engl J Med. 2012;366:1870-80. Adapted after Wolfgang Gaissmaier, with thanks. 1000 patients with natalizumab, anti-JCV− D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D Natalizumab should be used according to the SmPC
  20. 20. Anti JCV Ab Status and Weighing Risk of Disease vs Risks and Benefits of Treatment: AFFIRM D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D Patients with increase in disability 170 Patients with at least 1 relapse 280 Patients with hypersensitivity reactions 40 Patients developing PML in following 2 years 5 Patients with no significant harm 675 290 540 0 0 460 D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D Polman CH et al. N Engl J Med. 2006;354:899-910; Bloomgren G et al. N Engl J Med. 2012;366:1870-80. Adapted after Wolfgang Gaissmaier, with thanks. 1000 patients without natalizumab1000 patients with natalizumab, anti-JCV+ Natalizumab should be used according to the SmPC
  21. 21. Patient Leaflet Allowing Shared Decision Making http://multiple-sclerosis-research.blogspot.co.uk/2014/01/clinic-speak-what-is-high-pml-risk.html. Accessed February 21, 2014; Plavina T et al. Presented at CMSC; May 29–June 1, 2013; Orlando, FL. Poster DX.51. What is your risk of developing PML? What is your JC virus status? RISK FACTOR: Previous treatment with immunosuppressive (IS) drugs. These are drugs that reduce the activity of your body’s immune system. RISK FACTOR: TYSABRI treatment duration, especially over 2 years. Positive Negative Have you previously taken immunosuppressants? No Yes How long have you been on TYSABRI? 49−72 months 25−48 months 1−24 months Low PML risk High PML risk >1.5 1 in 10,000 1 in 1000 ≤0.9 ≤1.1 ≤1.3 ≤1.5 Ab level How long have you been on TYSABRI? 49−72 months 25−48 months 1−24 months 1 in 89 1 in 556 Insufficient data 1 in 10,000 ≤1.1 ≤1.3 ≤1.5 1 in 2500 1 in 1429 1 in 833 1 in 769 1 in 118 ≤0.9 >1.5 Ab level ≤1.1 ≤1.3 ≤1.5 1 in 3333 1 in 1429 1 in 1000 1 in 833 1 in 123 ≤0.9 >1.5 Ab level RISK FACTOR: Ab level is the level of anti-JCV antibodies in your blood. Natalizumab should be used according to the SmPC
  22. 22. Discussing Risk of Therapies with Patients: How Willing Are Patients to Accept Risk ? Heesen C et al. Mult Scler. 2010;16:1507-1512. Putative PML Risk Making Patients and Physicians Stop Natalizumab Neurologist should discuss concerns about MS and risk of treatment with each patient in order to tailor the treatment decision to each patient’s concerns 0 20 40 60 80 100 1/100,000 2/10,000 1/100 1/10 Persons(%) Physicians (n=66) Patients (n=69) Patients are willing to accept a higher risk of PML than neurologists
  23. 23. Value of PML Risk Stratification • Anti-JCV antibody-based PML risk stratification has enabled physicians and MS patients to make informed treatment decisions • Anti-JCV antibody status is the number one factor for PML risk stratification • Anti-JCV antibody testing is widely utilised in clinical practice – Unilabs in 2011: 32,108 tests – Unilabs in 2012: 45,709 (31,812 tests in new patients) Biogen Idec, data on file.
  24. 24. T2T - NEDA Zero tolerance Natalizumab and Alemtuzumab Are Changing Treatment Objectives in Relapsing MS Freedom from disease activity/ disease activity free Reduced ongoing damage Treat Early T2T=treat-to-target; NEDA=no evidence of disease activity; CNS=central nervous system. Holmén C et al. Mult Scler. 2011;17:708-719; Rudick RA et al. Ann Neurol. 2007;62:335-346; Havrdova E et al. Lancet Neurol. 2009;8:254-260; Gunnarsson M et al. Ann Neurol. 2011;69:83-89; Cohen JA et al. Lancet. 2012;380:1819-1828; Hartung HP et al. Presented at AAN; March 16–23, 2013; San Diego, CA. P07.093; Phillips J et al. Mult Scler. 2011;17:970-979; Butzkueven H et al. J Neurol Neurosurg Psychiatry. 2014 February. [Epub ahead of print].
  25. 25. T2T - NEDA Zero tolerance Natalizumab and Alemtuzumab Are Changing Treatment Objectives in Relapsing MS Freedom from disease activity/ disease activity free Reduced ongoing damage Potential for CNS repair Maintain reserve capacity Treat Early T2T=treat-to-target; NEDA=no evidence of disease activity; CNS=central nervous system. Holmén C et al. Mult Scler. 2011;17:708-719; Rudick RA et al. Ann Neurol. 2007;62:335-346; Havrdova E et al. Lancet Neurol. 2009;8:254-260; Gunnarsson M et al. Ann Neurol. 2011;69:83-89; Cohen JA et al. Lancet. 2012;380:1819-1828; Hartung HP et al. Presented at AAN; March 16–23, 2013; San Diego, CA. P07.093; Phillips J et al. Mult Scler. 2011;17:970-979; Butzkueven H et al. J Neurol Neurosurg Psychiatry. 2014 February. [Epub ahead of print].
  26. 26. T2T - NEDA Zero tolerance Natalizumab and Alemtuzumab Are Changing Treatment Objectives in Relapsing MS Freedom from disease activity/ disease activity free Reduced ongoing damage Potential for CNS repair Maintain reserve capacity Functional improvement Healthy aging Treat Early T2T=treat-to-target; NEDA=no evidence of disease activity; CNS=central nervous system. Holmén C et al. Mult Scler. 2011;17:708-719; Rudick RA et al. Ann Neurol. 2007;62:335-346; Havrdova E et al. Lancet Neurol. 2009;8:254-260; Gunnarsson M et al. Ann Neurol. 2011;69:83-89; Cohen JA et al. Lancet. 2012;380:1819-1828; Hartung HP et al. Presented at AAN; March 16–23, 2013; San Diego, CA. P07.093; Phillips J et al. Mult Scler. 2011;17:970-979; Butzkueven H et al. J Neurol Neurosurg Psychiatry. 2014 February. [Epub ahead of print].
  27. 27. T2T - NEDA Zero tolerance Natalizumab and Alemtuzumab Are Changing Treatment Objectives in Relapsing MS Freedom from disease activity/ disease activity free Reduced ongoing damage Potential for CNS repair Maintain reserve capacity Functional improvement Healthy aging Maintain or Improve Quality of Life Treat Early T2T=treat-to-target; NEDA=no evidence of disease activity; CNS=central nervous system. Holmén C et al. Mult Scler. 2011;17:708-719; Rudick RA et al. Ann Neurol. 2007;62:335-346; Havrdova E et al. Lancet Neurol. 2009;8:254-260; Gunnarsson M et al. Ann Neurol. 2011;69:83-89; Cohen JA et al. Lancet. 2012;380:1819-1828; Hartung HP et al. Presented at AAN; March 16–23, 2013; San Diego, CA. P07.093; Phillips J et al. Mult Scler. 2011;17:970-979; Butzkueven H et al. J Neurol Neurosurg Psychiatry. 2014 February. [Epub ahead of print].
  28. 28. Survival Analysis “Escalate early” MS is an autoimmune disease hypothesis 15–20 year experiment What Is Your Treatment Philosophy? Start Early, Develop Shared Goals, and “Treat for Response”
  29. 29. 18 15 51 70 0 20 40 60 80 100 Year 0–1 Year 1–2 PercentageofPatients (%) Placebo Natalizumab Overall at 2 years: 37% natalizumab vs 7% placebo (P<0.0001) Havrdová E. et al. Lancet Neurol. 2009;8:254-226. Natalizumab and Freedom from Disease Activity/ Disease Activity Free (AFFIRM) Freedom from Disease Activity/Disease Activity Free: Post hoc analysis of patients with no relapses, no sustained (12-week) disability progression, no Gd+ lesions, no new or enlarging T2-hyperintense lesions Non-Highly Active Disease <2 relapses in past 12 months or no Gd+ lesions at study entry 3 4 34 65 0 20 40 60 80 100 Year 0–1 Year 1–2 PercentageofPatients (%) n=248 n=458 n=228 n=407 n=59 n=146 n=56 n=137 P<0.0001 P<0.0001 P<0.0001 P<0.0001 Highly Active Disease ≥2 relapses in past 12 months and ≥1 Gd+ lesion at study entry
  30. 30. Managing to the Goals of Therapy Choosing therapy X Y Z Define the Individual’s MS No Treatment failure? Yes • Patient’s preferences? • Your choice? Individual measures: • Evidence of disease activity? • Tolerability/safety? • Adherence? • Drug or inhibitory markers? Monitoring • MS prognosis • Life style and goals • Shared goals for therapy Rebaseline Rebaseline: • IFNβ, natalizumab, fingolimod, terflunomide, DMF=3-6 months • Glatiramer acetate=9 months • Alemtuzumab=24 months DMF=dimethyl fumarate.
  31. 31. Managing to the Goals of Therapy Choosing therapy X Y Z Define the Individual’s MS No Treatment failure? Yes • Patient’s preferences? • Your choice? Individual measures: • Evidence of disease activity? • Tolerability/safety? • Adherence? • Drug or inhibitory markers? Monitoring • MS prognosis • Life style and goals • Shared goals for therapy Rebaseline Rebaseline: • IFNβ, natalizumab, fingolimod, terflunomide, DMF=3-6 months • Glatiramer acetate=9 months • Alemtuzumab=24 months “Treat early” DMF=dimethyl fumarate.
  32. 32. Managing to the Goals of Therapy Choosing therapy X Y Z Define the Individual’s MS No Treatment failure? Yes • Patient’s preferences? • Your choice? Individual measures: • Evidence of disease activity? • Tolerability/safety? • Adherence? • Drug or inhibitory markers? Monitoring • MS prognosis • Life style and goals • Shared goals for therapy Rebaseline Rebaseline: • IFNβ, natalizumab, fingolimod, terflunomide, DMF=3-6 months • Glatiramer acetate=9 months • Alemtuzumab=24 months “Treat early” “Choose treatments individually” DMF=dimethyl fumarate.
  33. 33. Managing to the Goals of Therapy Choosing therapy X Y Z Define the Individual’s MS No Treatment failure? Yes • Patient’s preferences? • Your choice? Individual measures: • Evidence of disease activity? • Tolerability/safety? • Adherence? • Drug or inhibitory markers? Monitoring • MS prognosis • Life style and goals • Shared goals for therapy Rebaseline Rebaseline: • IFNβ, natalizumab, fingolimod, terflunomide, DMF=3-6 months • Glatiramer acetate=9 months • Alemtuzumab=24 months “Treat early” “Choose treatments individually” “Monitor vigilantly” DMF=dimethyl fumarate.
  34. 34. Managing to the Goals of Therapy Choosing therapy X Y Z Define the Individual’s MS No Treatment failure? Yes • Patient’s preferences? • Your choice? Individual measures: • Evidence of disease activity? • Tolerability/safety? • Adherence? • Drug or inhibitory markers? Monitoring • MS prognosis • Life style and goals • Shared goals for therapy Rebaseline Rebaseline: • IFNβ, natalizumab, fingolimod, terflunomide, DMF=3-6 months • Glatiramer acetate=9 months • Alemtuzumab=24 months “Treat early” “Choose treatments individually” “Monitor vigilantly” “Switch confidently” DMF=dimethyl fumarate.
  35. 35. Key Takeaways • We are entering a new era of personalised medicine – Risk of disease being weighed against benefit and risk of treatment • Treatment goals changing? – Should we adopt treat-to-target from our rheumatology colleagues? – NEDA, TTT, and DAF have entered the neurology lexicon – Rebaselining will need to be agent specific • What is your treatment philosophy? – Escalation (treat for response) – Induction (treat for response) • How will you monitor for treatment response? – Incorporate MRI and rebaseline? • Risk stratification for PML and shared decision making – “Hit hard and early” is an important choice TTT=treat to target (T2T); DAF=disease activity free.

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