The time to act: Optimising patient careGavin GiovannoniQueen Mary University of London, UK

Who should take responsibility?

• The person with MS?

• The HCP or neurologist?

• The healthcare system?

• The regulators?

• Society?

HCP, healthcare practitioner; MS, multiple sclerosis.

Brain reserve and cognitive reserve in MS

ICV, intracranial volume; MS, multiple sclerosis; T2LL, T2 lesion load. Image adapted with permission from: Sumowski JF, et al. Neurology 2013;80:2186–2193.

Brain reserve protects against disease-related cognitive decline

Cognitive reserve independently protects against disease-related cognitive decline

over and above brain reserve

Intracranial volume

Ove

rall

cogn

itive

sta

tus

Early life cognitive leisure

Ove

rall

cogn

itive

sta

tus

Lower T2LL

Ove

rall

cogn

itive

sta

tus

0.0

‒0.5

‒1.0

‒1.5

Ove

rall

cogn

itive

sta

tus

0.0

‒0.5

‒1.0

‒1.5Higher T2LL

Lower leisureHigher leisure

Lower ICVHigher ICV

Lower T2LL Higher T2LL

MS non-specific

Brain Health

HRT, hormone replacement therapy; MS, multiple sclerosis.Image provided by Giovannoni G.

Therapeutic pyramid

Brain H

ealth Initiative

• Smoking• Exercise• Diet• Alcohol• Sleep• Comorbidities• Infections• Concomitant medications• Menopause/HRT?

MS-specific

Anti-inflammatory

Anti-neurodegenerative

Rem

yelin

atio

nN

euro

-res

tora

tion

Anti-ageing

PreventionDiagnosis

DMTSymptomatic

Therapist

Terminal

Counselling

Epstein Bar virus

Genetics

Vitamin D

Smoking

Risks

Adverse events

Differentialdiagnosis

At risk

RIS CIS Minimal impairment

Moderateimpairment

Severeimpairment

Terminal

Phase

MRI

Evokedpotentials

Lumbar puncture

BloodTests

DiagnosticCriteria

Cognition

Depression

Fatigue

Bladder

Bowel

Sexual dysfunction Tremor

PainSwallowing

SpasticityFalls

Balance problems Insomnia

Restless legsFertility

Clinical trials

Gait

Pressuresores

Oscillopsia

Emotionallability

Seizures

Gastrostomy

Rehab

Suprapubiccatheter Intrathecal

baclofen

Physio-therapy

Speech therapy

OccupationalTherapy

Functional neurosurgery

Colostomy

Tendonotomy

Studying

EmploymentRelationships

Travel

Vaccination

Anxiety

Driving

Nurse specialists

Family counselling

Relapses

1st line

2nd line

Maintenance Escalation Induction

Monitoring

Disease-free

Disease progression

DMTs

Side Effects

Advanced directive

Exercise

Diet

Alternativemedicine

PregnancyBreastfeeding

Research

Insurance

Visual loss

PalliativeCare

Assistedsuicide

Socialservices

Legalaid

Genetic counselling

Intrathecalphenol

Fractures

Movement disorders

Osteopaenia

Brain atrophy

Hearing loss

Tinnitus

Photophobia

Hiccoughs

DVLA

Neuroprotection

Psychosis

Depersonaliation

Brainhealth

Cognitivereserve

Sudden death

Suicide

OCD

Narcolepsy

Apnoea

Carers

Respite

Hospice

Respite

Dignitas

Advanced directive

Rhiztomy

Wheelchair

Walking aids

Blood/Organdonation

Brain donation

Exercise therapy

NABs

Autoimmunity

Infections

Outcome measures

Webresources

Pathogenesis

Doublevision

What isMS?

NEDA

T2TOCT

Neurofilaments

JCV statusPharma

Anaesthesia

CIS, clinically isolated syndrome; DMTs, disease-modifying therapies; DVLA, Driver and Vehicle Licensing Agency; JCV, John Cunningham virus; MRI, magnetic resonance imagery; NABs, neutralising antibody; NEDA, no evidence of disease activity; OCD, obsessive compulsive disorder; OCT, optical-coherence tomography; RIS, radiologically isolated syndrome, T2T, target-to-treat.Reproduced with permission from: Rieckmann P, et al. Mult Scler Relat Disord 2015;4:202–218.

MS non-specific

Brain Health

HRT, hormone replacement therapy; MS, multiple sclerosis.Image provided by Giovannoni G.

Therapeutic pyramid

Brain H

ealth Initiative

• Smoking• Exercise• Diet• Alcohol• Sleep• Comorbidities• Infections• Concomitant medications• Menopause/HRT?

MS-specific

Anti-inflammatory

Anti-neurodegenerative

Anti-ageing

Rem

yelin

atio

nN

euro

-res

tora

tion

Treatment effect on disability predicted by effect on T2-lesion load and brain atrophy

DIS, disability progression; EDSS, expanded disability status scale; MRI, magnetic resonance imaging; RRMS, relapsing remitting multiple sclerosis.Image adapted with permission from: Sormani MP, et al. Ann Neurol 2014;75:43-49.

Meta-analysis of treatment effect on EDSS worsening (y) vs. effects on MRI lesions and brain atrophy, individually or combined, in 13 placebo-controlled RRMS trials (13,500 patients)

0 0.2 0.4 0.6 0.8 1 1.2 1.4

0

0.2

0.4

00.6

0.8

1

1.2

1.4

1.6

1.8

2

ATROPHYeffect

DIS

effe

ct

0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

LESIONeffect

R2=0.61, p <0.001

DIS

effe

ct

0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6

0

0.2

0.4

00.6

0.8

1

1.2

1.4

1.6

1.8

2

LESION + ATROPHYeffect

R2=0.75, p<0.001 DIS

effe

ct

R2=0.48, p<0.001

Rapid adoption of innovations is“biggest unmet need of all”

Adapted from: Rogers EM, Diffusion of Innovations. New York, Free Press of Glencoe 1962.

Laggards

Late adopters

Majority adopters

Early adopters

~30% tipping point

Innovators

Time0%

50%

100%

Per

cent

age

of ta

rget

pop

ulat

ion

who

ado

pt

Large disparities exist in access to DMTs

DMT, disease-modifying therapy; MS, multiple sclerosis.Image provided by Giobannoni G. 1. Hollingworth S et al. J Clin Neurosci 2014;21:2083–2087; 2. World Bank, 2015. http://data.worldbank.org/indicator/SP.POP.TOTL. Accessed 27 May 2016;3. MSIF, 2013. http://www.atlasofms.org Accessed 27 May 2016; 4. Wilsdon T, et al. 2013. http://crai.com/sites/default/files/publications/CRA-Biogen-Access-to-MS-Treatment-Final-Report.pdf, Accessed 27 May 2016.

0 20 40 60 80 100

Newer DMTEstablished DMTNo DMT

All people with MS (%)

All data are from 2013

4

4

4

4

4

4

4

4

44

4

4

4

1–3

Established DMTsDMTs approved for relapsing forms of MS during the 1990s and reformulations or generic versions of these substances

Newer DMTsDMTs approved for relapsing forms of MS that have a different mechanism of action from established DMTs

Perf

orm

ance

Time

Old

New

Newer

www.msbrainhealth.org

International policy initiative

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.

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

Etc.

Clinical activity

Focal MRI activity

Hidden focal and diffuse MRI activity

Microscopic or biochemical pathology

Biomarkers

NEDA

END-

ORG

AN D

AMAG

E

Multiple sclerosis iceberg

MRI, magnetic resonance imaging; NEDA, no evidence of disease activity. Images reproduced with permission from: http://multiple-sclerosis-research.blogspot.com/2015/07/cortical-lesions-and-cognitive-ability.html Accessed 27 May 2016.

Stroke or brain attack: ‘time really is brain’

Passive Active

Early intervention and long-term prognosis

www.msbrainhealth.orgImage reproduced with permission from Giovannoni G, et al. Brain health: Time matters in multiple sclerosis. 2015 Available at www.msbrainhealth.org/report Accessed 26 May 2016.

Incr

easi

ng d

isab

ility

Time

Intervention at diagnosis

Intervention later

Potentialrange ofoutcomes

No treatment

Later intervention

Intervention at diagnosis

Barts-MS: 2016 Brain Health Challenge

Treat-2-Target

Lifestyle

Comorbidities

Wellness 2016Brain Health

Challenge

Barts-MS

Barts-MS: 2016 Brain Health Challenge

MS, multiple sclerosis; NEDA, no evidence of disease activity ,

• Prognosis• Active MS• Treatment• Re-baselining• Monitoring• NEDA

Treat-2-Target

Lifestyle

Comorbidities

Wellness

Barts-MS: 2016 Brain Health Challenge

• Diet & supplements• Exercise• Smoking• Alcohol• Sleep• Stress

Treat-2-Target

Lifestyle

Comorbidities

Wellness

Barts-MS: 2016 Brain Health Challenge

• Obesity• Hypertension• Glucose• Cholesterol• Smoking• Sleep disorders• Infections• Falls• Depression & anxiety• Concomitant medications

Treat-2-Target

Lifestyle

Comorbidities

Wellness

Barts-MS: 2016 Brain Health Challenge

• Intellectual• Emotional• Physical• Social• Spiritual• Occupational• Environmental

Treat-2-Target

Lifestyle

Comorbidities

Wellness

“Our vision is to create a better future for people with MS and their families”