patient activation - making treatment decisions

Making Treatment Decisions

Gavin Giovannoni

Disclosures

I have 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, Almirall, 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.

Expert Patient

‘When acute disease was the primary cause of illness,patients were generally inexperienced and passiverecipients of medical care. Now that chronic illness hasbecome the principle medical problem, the patientmust become a co-partner in the process’

(Holman & Lorig 2000)

Concordance modelCompliance model

Neurologist decides diagnosis and treatment

Neurologist’s task is to explain and instruct

Neurologist’s task is to comprehend

Successful outcome is compliance

Neurologist and patient negotiate diagnosis and treatment

Neurologist elicits, explains, persuades and accommodates

Patient explains, considers and accommodates

Successful outcome is a negotiated agreement

Moving from compliance to concordance requires a culture change

Source: From Compliance to Concordance, 1997Compliance vs. Adherence

What is your worldview?

www.ms-res.org

Epstein Bar Virus

Genetics

Vitamin D

Smoking

Risks

Adverse events

DifferentialDiagnosis

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

Prevention

Diagnosis

DMT

Symptomatic

Therapist

Terminal

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

What is multiple sclerosis?

www.ms-res.org

Are you sure you have MS?

Engell T. Acta Neurol Scand. 1988 Jul;78(1):39-44.

518 definite MS 418 (94%) MS

33 (6%) not-MS

Post-mortem

33 Probable MS22 (66%) MS

11 (33%) not-MS

Post-mortem

Other diagnoses or “MS mimics”

• ADEM

• Ageing

• Behcet’s syndrome

• Cerebrovascular disease

• Decompression sickness

• Fat embolism

• HIV encephalitis

• HTLV1-associated myelopathy

• Hydrocephalus

• irradiation

• Leukodystrophies

• Migraine

• Mitochondrial encephalopathy

• MND

• Neurosarcoidosis

• Phenylketonuria

• PML

• SSPE

• SLE/APL

• Trauma

Miller DH. (1997)

Kleinschmidt-DeMasters,et al. N Engl J Med. 2005 Jul 28;353(4):369-74.

Infection (PML) complicating treatment with natalizumab

What types of MS do you have?

RRMS R-SPMS/NR-SPMS PPMS RPMS

relapsing forms of MS vs. non-relapsing MS

Licensed treatments

What prognostic group do you fall into?

Favourable

Indeterminate

Poor

timeAim of

treatment

Prognostic factors

1. Older age of onset (greater than 40 years)2. Male sex3. “Multifocal“ onset (more than one site in the nervous system involved)4. Efferent system affected (motor/weakness, cerebellar, bladder)5. Partial or no recovery from initial relapses6. High relapse rate in the first 2 years (more than 2 relapses)7. Disability after 5 years (EDSS > 3.0)8. Abnormal MRI with large lesion load (more than 9 lesions on MRI)9. Lesion location - posterior fossa lesions (lesions in the back of the brain)10. Brain atrophy (shrinkage of the brain)11. Spinal fluid positive for OCBs (oligoclonal IgG bands)12. Low vitamin D levels13. Raised neurofilament levels in your spinal fluid (this test is not part of routine care

unless you live in Sweden)14. Smoker (smokers with MS do worse than non-smokers)15. Co-morbidities (e.g. diabetes, hypertension and raised cholesterol)16. Genomic factors (e.g. ApoE4; this is risk factor for Alzheimer's disease and some

other degenerative brain diseases; not everyone in the field accepts this as a poor prognostic factor)

http://multiple-sclerosis-research.blogspot.com/2014/02/clinic-speak-what-prognostic-group-do.html

What is the risk of you not being

treated?

www.ms-res.org

What is the risk of you not being treated?

www.ms-res.org

What is active MS?

2001Clinical

2009Clinical and MRI

2014Clinical or MRI

Inactive MS: no relapses or MRI activity in the last 24 months

Active MS: relapses in the last 12 or 24 months and/or MRI activity in the last 12 months

Am I eligible for treatment

2001Clinical


2014Clinical or MRI

Inactive MS: no relapses or MRI activity in the last 24 months


Highly active MS: relapses in the last 12 months and MRI activity in the last 12 months

Rapidly-evolving severe MS (RES); two disabling attacks in a 12

month period and MRI evidence of activity during this period.

No treatmentNatalizumab

(Tysabri)Fingolimod (Gilenya)

Treatment

Aim of treatment

2001Clinical


2014Clinical or MRI

Inactive MS: no relapses or MRI activity in the last 24 months (NEDA)


Highly active MS: relapses in the last 12 months and MRI activity in the last 12 months

Rapidly-evolving severe MS (RES); two disabling attacks

in a 12 month period and MRI evidence of activity during

this period.

1st-line A

1st-line B

1st-line C

1st-line D

1st-line E

2nd-lineN

2nd-lineM

3rd-liney

3rd-lineX

Do you understand the difference between maintenance-escalation and induction therapies?

Flipping the pyramid

IMS, immunosuppressant; TNF, tumour necrosis factorReproduced from Gut, Ordás I, Feagan BG and Sandborn WJ, 1754–63, 2011 with permission from BMJ Publishing Group Ltd.

Conventionalstep care

TNFantagonist

± IMS

Corticosteroids+ IMS

Corticosteroids


Corticosteroids

TNFantagonist

± IMS

TNFantagonist

± IMS



TNFantagonist

± IMS


Corticosteroids


Acceleratedstep care

Moderate

Severe

IMS + TNFantagonist

Early top-down

Le

ve

l of

dis

ea

se

Flipping the pyramid

Do you understand treating to target of no evident disease activity (NEDA)?

• NEDA = NEDD (no evident detectable disease) in the field of cancer

• Treat-2-target was first used in the treatment of rheumatoid arthritis

Treat-2-target

What is NEDA?

× No relapses× No disability progression (EDSS)× No MRI activity

BARTS-MS ALGORITHM

Choose therapy

A B C

Define the individual’s MS

Treatment failure?

• Patient’s preferences?• Your choice?

Individual measures:• Evidence of disease activity?• Tolerability/safety?• Adherence?• Drug or inhibitory markers,

e.g. NABs?

Monitoring

• MS prognosis based on clinical and MRI indices

• Life style and goals • Shared goals for therapy

Rebaseline

Rebaselining:• ifn-β, natalizumab, fingolimod,

teriflunomide, dimethyl-fumarate=3-6 months

• glatiramer acetate=9 months• alemtuzumab=24 months

Choose a therapeutic strategy

Maintenance-escalation Induction

Choose therapy

X Z

Rebaseline

Monitoring

Initiate or Switch or Escalate Rx Complete course / Re-treat

Breakthrough disease

Y

• Patient’s preferences?• Your choice?

NoYes Yes

• Only one licensed induction therapy at present

Ifn-β = interferon-beta; NABs = neutralizing antibodies; Rx = treatment Disclaimer: data presented on this slide reflects the algorithm at Barts-MS and is not a Biogen recommendation

www.ms-res.org

www.msbrainhealth.org

Patient engagement in their own healthcare

has been described as the ‘blockbuster drug

of the century’.

Achieving patient engagement in multiple sclerosis: A perspective from the multiple

sclerosis in the 21st Century Steering Group 2015

patient activation - making treatment decisions

Health & Medicine