Top 10 Research Findings of 2016

Transcription

1 Top 10 Research Findings of 2016 NMSS Regional Summit 2017 June 10, 2017 Rebecca Spain, MD, MSPH VA Portland Health Care System Oregon Health & Science University

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3 Disclosures Research support: NMSS Department of Veterans Affairs Conrad Hilton Foundation Biogen idec 3

4 Learning objectives 1. Identify potential disease modifying therapies for progressive MS 2. Investigate progressive MS using long term studies 3. Understand the role of wellness in MS risk and prognosis 4. Recognize the impact of the health care environment on MS 4

5 Potential treatments for progressive MS #10: Spain et al: Lipoic acid (LA) in SPMS Oral antioxidant Traces found in foods Improves animal model, EAE

6 Pilot trial of 1200mg LA in SPMS 2-year study 1. Is LA is superior to placebo for neuroprotection (brain atrophy)? 2. Can LA reduce disability? 3. Is LA is safe?

7 Table 1. Baseline demographics Lipoic Acid (n = 27) Placebo (n = 24) Age, years + SD Women, % Caucasian, % MS duration, years + SD Education > high school, % EDSS, (range) 5.5 ( ) 6 ( ) Taking DMT, % Spain et al. Neurology: Neuroimmunology and Neuroinflammation, accepted

8 Primary outcome: change in whole brain atrophy 68% P = Spain et al. Neurology: Neuroimmunology and Neuroinflammation, accepted

9 Potential treatments for progressive MS #9: Tourbah et al: Biotin (MD1003) in Prog MS 10,000 recommended dose Cofactor for 4 carboxylases May repair myelin (via fatty acid synthesis) May be anti-oxidative (via intermediaries for TCA cycle) In pilot open-label trial (n=23), >90% improved 12 month RCT with 12 month open-label extension Tourbah et al. Mult Scler 2016;22:

10 Table 1. Baseline demographics MD1003 (n = 103) Placebo (n = 51) Age, years + SD Women, % PPMS, % MS duration, years + SD EDSS, median (range) 6.0 ( ) 6.0 ( ) TW25 (sec), mean + SD Taking DMT, % Tourbah et al. Mult Scler 2016;22:

11 N=13, 77% improved on EDSS Primary outcome Tourbah et al. Mult Scler 2016;22:

12 Mean change from baseline EDSS Tourbah et al. Mult Scler 2016;22:

13 Investigate progressive MS using long term studies #8: Kappos et al: 11 year f/u BENEFIT CIS trial Betaferon/Betaseron in Newly Emerging MS for Initial Treatment 5:3 randomization w/in 60 days of CIS (2 MRI lesions) After CDMS or 2 years, placebo could switch to treatment Kappos L et al. Neurology 2016;87:

14 11 year f/u BENEFIT CIS trial BENEFIT n= 468 Interferon beta-1b n=292 Placebo n=196 Enrolled BENEFIT 11 n= 167 Enrolled BENEFIT 11 n= % risk reduction conversion to CDMS Without CDMS = 45% Without CDMS = 39% With CDMS = 55% With CDMS = 61% SPMS = 4.5% SPMS = 8.3%, p=0.49 Kappos L et al. Neurology 2016;87:

15 Investigate progressive MS using long term studies #7: Relationship of age and MS phenotype ARR is common clinical outcome in RCTs What is r ole of age in ARR and PMS occurrence? London, Ontario database Patients accrued Followed until with progressive MS analyzed (71% SPMS) Scalfari et al. Mult Scler 2016;22:

16 Effect of relapses on age of onset of progression (a) More attacks (purple) marginally influenced age of onset of PMS (b) Total number of attacks did not influence age of onset of PMS YEARS Published in: A Scalfari; C Lederer; M Daumer; R Nicholas; GC Ebers; PA Muraro; Multiple Sclerosis Journal 22, DOI: / Copyright 2016 SAGE Publications

17 Regardless of number of attacks and duration RR phase 1. Age of onset of PMS was remarkably similar 2. Disability progression during progressive phase the same Published in: A Scalfari; C Lederer; M Daumer; R Nicholas; GC Ebers; PA Muraro; Multiple Sclerosis Journal 22, DOI: / Copyright 2016 SAGE Publications

18 Role of wellness in MS risk and prognosis #6: Vascular comorbidities prior to & after MS diagnosis Comorbidites may affect risk and severity of MS If they co-occur at diagnosis, are there shared underlying mechanisms (and treatments?) Danish case-control study 18

19 Danish case-control study Included MS diagnosed Assessed for cardiovascular and cerebrovascular comorbidities from: 1977 to diagnosis diagnosis to Thormann et al. J Neurol 2016;263:

20 Cerebrovascular comorbidity (1 year after MS onset) Cardiovascular comorbidity (at MS onset) HR 1.84 (95% CI , p < HR 1.08 (95 % CI , p = 0.013) MS Controls MS Controls 20 Thormann et al. J Neurol 2016;263:

21 Role of wellness in MS #5: Low-fat, plant-based diet in MS 21 Yadav et al. Mult Scler Relat Disord 2016;9:80-90.

22 Secondary outcome: Diet participants had improved fatigue CONTROL P = 0.27 DIET P = Yadav et al. Mult Scler Relat Disord 2016;9:80-90.

23 Changes in BMI and LDL cholesterol CONTROL P = ns DIET P < CONTROL P = ns DIET P = ns 23 Yadav et al. Mult Scler Relat Disord 2016;9:80-90.

24 Role of wellness in MS #4: Alterations of human gut microbiome in MS Implicated in autoimmune disorders Altering gut microbiome affects disease susceptibility and severity in EAE Altering gut microbiome may treat EAE Authors survey gut microbiome, correlate with clinical factors 24 Jangi et al. Nat Commun 2016;7:12015

25 60 mild MS 43 controls 41 MS 32 controls 25 Jangi et al. Nat Commun 2016;7:12015

26 Figure 2. Compositional differences in faecal microbiota between MS patients & healthy subjects. 26 Jangi et al. Nat Commun 2016;7:12015

27 Fig. 4. Measurement of breath methane production in MS patients (n=41) and controls (n=32). 27 Jangi et al. Nat Commun 2016;7:12015

28 Impact of the health care environment on MS #3: Spectrum of misdiagnosis in MS 28 Solomon et al. Neurology;87:

29 Andrew J. Solomon et al. Neurology 2016;87: American Academy of Neurology

30 Impact of the health care environment on MS #2: Health insurance affects use of DMT in MS Wang et al. Neurology 2016; 87:

31 Figure 1 Disposition of respondents by disease-modifying therapy (DMT) use and insurance challenges Guoqiao Wang et al. Neurology 2016;87:

32 Guoqiao Wang et al. Neurology 2016;87:

33 Impact of the health care environment on MS #1: Cost of DMTs ocrelizumab

34 Thank You

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