The importance of early intervention clinician perspective. Øivind Grytten Torkildsen

Transcription

1 The importance of early intervention clinician perspective Øivind Grytten Torkildsen

2 «You can never diagnose MS too late» Neuroradiologist from Norway, early 1990s

3 Prognosis in untreated MS

4 Early diagnosis RIS CIS RRMS SPMS Cerebral Volume Relapses and Disability MRI Lesion Load MRI Activity Trapp BD et al. Neuroscientist. 1999;5:48-57.

5 Probability Employment in untreated MS Probability of Remaining in Active Employment After Onset of MS 1.0 Control Persons MS Patients Time (years) Pfleger CC et al. Mult Scler. 2010;16:

6 Proportion of Patients 65 Years Old Working (%) Employment Change with EDSS Score Increase Austria Belgium Germany Italy Netherlands Spain Sweden Switzerland United Kingdom / /9.0 EDSS Score Adapted from Kobelt G et al. J Neurol Neurosurg Psychiatry. 2006;77:

7 Utility (EQ-5D: 0=Death; 1=Full Health) Quality of life decreases with increasing EDSS-score EDSS Score 1.00 Best Possible Health Status 0.00 Worst Possible Health Status 0.85 mean utility of normal population mean utility of aging patients with osteoporosis, no fracture mean utility of patients with rheumatoid arthritis at stage mean utility of patients with Parkinson s disease mean utility of patients with MS mean utility of severe hemophilia patients with inhibitors 5

8 Survival in untreated MS 8 years decreased survival

9 In other words 1977

10 After 10 years: 1/4 of MS-patients have died from the disease 1/4 are still employed 1/2 are not employed, with different degrees of disability

11 What happens in MS Acute damages

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13 Normal White Matter Animasjon basert fra Trapp BD et al. N Engl J Med. 1998;338:278

14 Active Lesion Animasjon basert fra Trapp BD et al. N Engl J Med. 1998;338:278

15 Chronic Active Lesion Animasjon basert fra Trapp BD et al. N Engl J Med. 1998;338:278

16 Chronic Inactive Lesion Animasjon basert fra Trapp BD et al. N Engl J Med. 1998;338:278

17 Trapp BD et al. N Engl J Med. 1998;338:278

18 Trapp BD et al. N Engl J Med. 1998;338:278

19 Transected axons in different MSlesions Number of Transected Axons Per Mm Active 3138 Chronic Active Edge 875 Chronic Active Core 17 NAWM 0.7 Control Trapp BD et al. N Engl J Med. 1998;338:278

20 Number of damaged axons by disease duration Number of APP-Positive Axons per mm <1 Year 1 5 Years 5 10 Years >10 Years Disease Duration Increasing acute axonal damage Kuhlmann T et al. Brain. 2002;125(Pt 10):

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22 What happens in progressive MS?

23 Ann Neurol Feb;71(2):227-44

24 Ann Neurol Feb;71(2):227-44

25 Ann Neurol Feb;71(2):227-44

26 Mitochondrial damage? Lassmann, 2013

27 Prognosis with treated MS

28 Early treatment significantly reduced the risk of EDSS-progression Ann Neurol Oct;66(4):513-20

29 Goodin DS, et al Neurology;78(17):

30 Ann Neurol Jan;73(1):95-103

31 New MRI-lesions during MS-treatment 100 predict disability progression None No. of New T2-Hyperintense Lesions After 1 Year of Therapy *Sustained disability progression was defined as a 1.0-point increase in EDSS score confirmed at 6 months. Mean follow-up was 4.8 years. Prosperini L et al. Eur J Neurol. 2009;16:

32 J Neurol Jan;253(1):98-108

33 Summary Early treatment most effective Disease activity during treatment poorer prognosis

34 Introduction of RRMS Therapies in the EU Outcome Measures Goals of Therapy Address Symptoms Slow Disease Progression Stop Disease Progression Repair No Evidence of Disease Activity (NEDA) Sustained improvement SC IFNβ-1b 1995 IM IFNβ-1a 1997 SC IFNβ-1a 1998 GA Natalizumab Fingolimod 2010 Mitoxantrone 2000 DMF Peginterferon Beta-1a 2014 Alemtuzumab Teriflunomide 2013?

35 No Evidence of Disease Activity (NEDA) No relapses Relapses EDSS-progression No EDSS progression MRI activity No new T2-lesions No new Gd+-lesions Imitola J, Racke MK. JAMA Neurol. 2015;72: ; Stangel M et al. Ther Adv Neurol Disord. 2015;8:3-13.

36 Disability Early Treatment vs Later Treatment Late treatment Disease onset Time Adapted from Miller JR. J Manag Care Pharm. 2004;10(suppl S-b):S4-S11. 36

37 Disability Early Treatment vs Later Treatment Window of opportunity Late treatment Effective treatment at diagnosis Disease onset Time Adapted from Miller JR. J Manag Care Pharm. 2004;10(suppl S-b):S4-S11. 37

38 Summary MS is a serious disease, if untreated. Early and effective treatment can alter the prognosis.

39 "When you change the way you look at things, the things you look at change. Max Planck