1) The document discusses the importance of early intervention in multiple sclerosis (MS) to maximize long-term brain health and prevent disability progression over time. 2) It promotes a strategy of treating MS patients aggressively early on to minimize clinical relapses, focal lesions detected by MRI, and underlying brain atrophy. 3) The goal is to create an initiative called MS Brain Health that encourages adopting a therapeutic approach aiming to optimize brain health for all people living with MS through their lifetime.

1. Brain Health: why time matters in MS
MS Trust Conference 2018
Gavin Giovannoni

2. Disclosures
Over the last 5 years I have received personal compensation for participating in
advisory boards in relation to clinical trial design, trial steering committees, and
data and safety monitoring committees from: Abbvie, Atara Bio, Biogen, Canbex,
Sanofi-Genzyme, Genentech, GSK, MSD, Merck-Serono, Novartis, Roche,
Synthon BV and Teva.

3. ESRF: end-stage renal failure

4. Rheumatoid arthritis: end-stage joint disease

5. Early intervention and long-term prognosis
www.msbrainhealth.org
Giovannoni G, et al. Brain health: Time matters in multiple sclerosis. 2015 Available at www.msbrainhealth.org/report
Increasingdisability
Time
Intervention
at diagnosis
Intervention
later
Potential
range of
outcomes
No treatment
Later intervention
Intervention at diagnosis

6. Relapses
Unreported relapses
Clinical disease progression
Subclinical relapses: focal MRI activity
Focal gray and white matter lesions
not detected by MRI
Brain atrophy
Spinal fluid neurofilament levels
MS Iceberg - Treat-2-Target
Clinical activity
Focal MRI activity
Hidden focal and diffuse MRI activity
Microscopic or biochemical pathology
Biomarkers

7. Stroke or brain attack: ‘time really is brain’
Passive Active

8. Neuro-restoration
Remyelination
Neuroprotection
Anti-inflammatory
Therapeutic pyramid
Anti-ageing
BrainHealthInitiative
• Smoking
• Exercise
• Diet
• Alcohol
• Sleep
• Comorbidities
• Infections
• Concomitant medications
MS-specific
MS non-specific
• ? menopause/HRT
What is brain health?

9. 0 20 40 60 80 100
Large disparities exist in access to disease-modifying therapies
DMT, disease-modifying therapy. 1. Hollingworth S et al. J Clin Neurosci 2014;21:2083–7;
2. World Bank, 2015. http://data.worldbank.org/indicator/SP.POP.TOTL; 3. MSIF, 2013. http://www.atlasofms.org; 4. Wilsdon T et al. 2013. http://crai.com/sites/default/files/publications/CRA-Biogen-Access-to-MS-Treatment-Final-Report.pdf.
Figure reproduced from Giovannoni G et al. Brain health: time matters in multiple sclerosis. Available at: www.msbrainhealth.org
Newer DMT
Established DMT
No DMT
All people with MS (%)
All data are from 2013
4
4
4
4
4
4
4
4
4
4
4
4
4
1–3
Established DMTs
DMTs approved for relapsing
forms of MS during the
1990s and reformulations or
generic versions of these
substances
Newer DMTs
DMTs approved for relapsing
forms of MS that have a
different mechanism of
action from established
DMTs

10. MS Brain Health vision and aim*
*Defined by MS Brain Health Steering Committee in 2015
Our overarching aim is to encourage the
widespread adoption of a therapeutic strategy
that aims to maximize the lifelong brain
health of every person with MS
Our vision is to create a better future for
people with MS and their families

11. International policy initiative
www.msbrainhealth.org
DMT, disease-modifying therapy.
Images used with permission from Giovannoni G, et al. Brain health: Time matters in multiple sclerosis. 2015 www.msbrainhealth.org/report. Accessed 26 May 2016.

12. Next steps for the MS Brain Health initiative
1. Expand our supporter base
2. Continue global dissemination of
evidence
3. Focus on consensus statements from
Delphi research
4. Consult widely about tools for healthcare
professionals and people with MS
5. Trial them in selected centres
Healthcare
professionals
People with MS
and advocates
Payers and
HTA bodies
Policy
makers
Media
and PR
Audiences

13. Consensus standards structured around the
key stages in the MS care pathway
Symptom
onset
Referral &
diagnosis
Treatment
decisions
Brain-healthy
lifestyle
Monitoring
MS
Managing
relapses

14. From checklist to ‘MS Advisor’ app: our vision
msadvisor
MS Advisor

15. msadvisor Barts-MS, Royal London Hospital
Whitechapel, London E1 1BB
Overall
Diagnosis
Monitoring
DMTs
Co-morbidities
Education
Relapses
62 reviews
38.6 days
868 MSers
54%
8.3 days
1211 MSers
187 reviews
Contact Staff Services For you search

16. Neuro-restoration
Remyelination
Neuroprotection
Anti-inflammatory
Therapeutic pyramid
Anti-ageing
BrainHealthInitiative
• Smoking
• Exercise
• Diet
• Alcohol
• Sleep
• Comorbidities
• Infections
• Concomitant medications
MS-specific
MS non-specific
• ? menopause/HRT
What is brain health?

17. Vascular Comorbidity Accelerates Disability
Progression!
Marrie et al. Neurology 2010;74:1041–1047.

18. Conclusions
• MS is a bad disease
• Mortality, disability, unemployment, divorce, cognitive impairment, etc.
• On average early effective therapy is the only realistic option of preventing end-organ damage
• NEDA and T2T are current treatment target (zero tolerance)
• Beyond NEDA we need to target end-organ damage (brain atrophy, CSF NF levels, etc.)
• Non-MS specific mechanisms
• Comorbidities
• Con-meds
• Ageing
• Self monitoring revolution to promote #BrainHealth
• Brain Health initiative
• Are you prepared to join the challenge?
• #Run4MS - parkrun
#BrainHealth

19. #Run4MS