from compliance to adherence can todays situation improve ? emsp information day brussels, 13...

M Sandberg 2008-11-13M Sandberg 2008-11-13

From Compliance to From Compliance to AdherenceAdherence can today’s situation improve can today’s situation improve ? ?

EMSP Information DayEMSP Information Day

Brussels, 13 November 2008Brussels, 13 November 2008

Magnhild Sandberg-WollheimMagnhild Sandberg-Wollheim


Why are patients Why are patients with MS not with MS not compliant?compliant?


Prognosis of MS Prognosis of MS yesterdayyesterday 35 years ago two young men were 35 years ago two young men were

diagnosed with “optic neuritis” – diagnosed with “optic neuritis” – – a common first symptom of MSa common first symptom of MS

At that time, At that time, – we had no prognostic markers we had no prognostic markers – we had no Disease Modifying Treatmentswe had no Disease Modifying Treatments

So what has happened?So what has happened?


Prognosis of MS Prognosis of MS yesterdayyesterday One of them One of them

– never had another attack and has remained never had another attack and has remained healthyhealthy

The other man The other man – had several attacks over the next few yearshad several attacks over the next few years– eventually needed a wheelchair to move eventually needed a wheelchair to move

aroundaround– and became tetraplegic and became tetraplegic


Prognosis of MS todayPrognosis of MS today

We still have no prognostic markersWe still have no prognostic markers We still have no cure, BUTWe still have no cure, BUT We do have DMTsWe do have DMTs

So why are patients not compliantSo why are patients not compliant– the disease is not an immediate threatthe disease is not an immediate threat– but we know from natural history studies but we know from natural history studies

that 50% will have progressive disease that 50% will have progressive disease after after ~~15 yrs15 yrs


Adherence to long-term Adherence to long-term

therapytherapy

For chronic illnesses in developed For chronic illnesses in developed countries countries adherence is only adherence is only ~50%~50%

NonNon-adherence rates in -adherence rates in – diabetes 36-87%diabetes 36-87%– hypertension 33-84%hypertension 33-84%– cancer (oral drugs) 20-100%cancer (oral drugs) 20-100%


‘‘Increasing the Increasing the effectiveness ofeffectiveness of adherence interventionsadherence interventions may have a may have a far greater impact on the health of the far greater impact on the health of the population than any improvement in population than any improvement in specific medical treatments’specific medical treatments’

Haynes RB et al. Haynes RB et al. Cochrane Database Syst Rev 2005;4:CD000011


Definition of Definition of AdherenceAdherenceWHO 2003WHO 2003

‘‘The extent to which a person’s behaviour – The extent to which a person’s behaviour – taking medication, following a diet, and/or taking medication, following a diet, and/or executing lifestyle changes – corresponds executing lifestyle changes – corresponds with with agreed recommendationsagreed recommendations from a from a healthcare providerhealthcare provider’’

Adherence to Long-term Therapies: Evidence for Action, WHO 2003, ISBN 92 4 154599 2www.emro.who.int/ncd/Publications/adherence_report.pdf


Adherence vs Adherence vs ComplianceComplianceWHO 2003WHO 2003

AdherenceAdherence – requires that requires that patient has agreedpatient has agreed with with

treatment recommendationstreatment recommendations– stresses that stresses that patient has a choicepatient has a choice of of

whether or not to follow treatment whether or not to follow treatment recommendations recommendations

– is preferred to ‘compliance’ as this implies is preferred to ‘compliance’ as this implies that the patient is passive in decision-that the patient is passive in decision-making processesmaking processes


Consequences of poor Consequences of poor treatment adherencetreatment adherence Treatment outcomes will be poor in Treatment outcomes will be poor in

the the short termshort term – may negatively affect adherence, resulting may negatively affect adherence, resulting

in a vicious circle in a vicious circle

Disease sequelae in the Disease sequelae in the long termlong term

High health-care High health-care costs costs – patients with severe disability are costlypatients with severe disability are costly


What is the cost in What is the cost in money?money?

MS: Low Prevalence MS: Low Prevalence Compared to other disorders of the brainCompared to other disorders of the brain

-

5

10

15

20

25

30

35

40

45

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ise

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Source: Sobocki et al, Eur J Neurology 2005;12(S1)

MS: High Cost per MS: High Cost per PatientPatientCompared to other disorders of the brainCompared to other disorders of the brain

0

5 000

10 000

15 000

20 000

25 000

30 000

35 000

40 000

Co

st p

er p

atie

nt

(€ 2

004)

tum

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r

mu

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cler

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ke

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Source: Sobocki et al, Eur J Neurology 2005;12(S1)

Cost of MS in Sweden in Cost of MS in Sweden in 20052005Results – Cost by severity (N=1339)Results – Cost by severity (N=1339)

0

20 000

40 000

60 000

80 000

100 000

120 000

0-1 2 3 4 5 6 6.5 7 8-9

EDSS

Me

an

co

st

pe

r p

ati

en

t a

nd

ye

ar

(€ 2

00

5)

Early retirement

Short-term absence

Informal care

Services

Investments

Other Rx and OTC drugs

Disease modifying drugs

Tests

Ambulatory care

Inpatient care

8.0% 11.6% 9.4% 6.9% 13.0% 13.5% 12.1% 8.4% 16.8%Proportion of patients

Source: Berg J, Lindgren P, Fredrikson S, Kobelt G. Eur J Health Economics 2006;7(S2):77-87


Existing DMDs for MSExisting DMDs for MS

Self-injectablesSelf-injectables– interferon beta (IFNinterferon beta (IFNββ), glatiramer acetate ), glatiramer acetate

(GA)(GA)– intramuscular or subcutaneousintramuscular or subcutaneous– daily, every other day, thrice weekly, once daily, every other day, thrice weekly, once

weeklyweekly

Hospital injectionsHospital injections– natalizumab (and mitoxantrone off-label)natalizumab (and mitoxantrone off-label)– intravenousintravenous– every four weeks (or every three months)every four weeks (or every three months)


Factors with a negative Factors with a negative effect on adherence to effect on adherence to treatmenttreatment Needle phobia or anxietyNeedle phobia or anxiety

– is present in approx 10-20% of the populationis present in approx 10-20% of the population– is more common with self-injectionsis more common with self-injections– may need to involve family or friends or healthcare may need to involve family or friends or healthcare

providers providers

Difficulty with administrationDifficulty with administration– reduced manual dexterity reduced manual dexterity – cognitive impairmentcognitive impairment

Time needed for administrationTime needed for administration– from daily to weekly regimensfrom daily to weekly regimens

Cohen & RieckmannInt J Clin Pract 2007;61:1922–30


Factors with a negative Factors with a negative effect on adherence to effect on adherence to treatmenttreatment Injection site reactionsInjection site reactions

– pain, bruising, infiltrates, abscesses pain, bruising, infiltrates, abscesses

Adverse effects Adverse effects – fever, influenza like symptoms, headache fever, influenza like symptoms, headache – liver and thyroid function tests abnormal liver and thyroid function tests abnormal – depressiondepression– fatiguefatigue

Disruption of life-style Disruption of life-style

Unrealistic expectationsUnrealistic expectations

Cohen & Rieckmann. Int J Clin Pract 2007;61:1922–30


What happens in clinical What happens in clinical practice?practice?


In clinical practiceIn clinical practice

9-20% 9-20% disdiscontinue treatment in continue treatment in the first 6 monthsthe first 6 months

~40% do not restart therapy~40% do not restart therapy

Discontinuation of existing Discontinuation of existing DMDs in clinical practiceDMDs in clinical practice

DMD, disease-modifying drug; GA, glatiramer acetate; IFN, interferon1Tremlett HL, Oger J. Neurology 2003;61:551–42O’Rourke KET, Hutchinson M. Mult Scler 2005;11:46–503Rio J et al. Mult Scler 2005;11:306–9

>3 years’ follow up1 4 years’ follow up34 years’ follow up2

IFN beta 0

10

20

30

40

IFN beta IFN beta or GA

Dis

co

nti

nu

ati

on

ra

te (

%)

39% (79/203)

17% (107/622)

28% (109/394)

Courtesy Merck Serono

Reasons for discontinuation Reasons for discontinuation of IFN betaof IFN beta

30%

12%10% 9% 8% 7% 6%

0

5

10

15

20

25

30

Perceived lack of

efficacy

Injection-site

reactions

Flu-like symptoms

Depression Headache Liver test abnormalities

Fatigue

Pat

ien

ts (

%)

giv

ing

th

at r

eas

on

fo

r in

terr

up

tio

n o

f >

1 m

on

th

IFN, interferonTremlett HL, Oger J. Neurology 2003;61:551–4

Perceived lack of efficacyPerceived lack of efficacy and and occurrence of occurrence of side-effectsside-effects were were the main reasons cited by patients the main reasons cited by patients who discontinued IFN beta therapywho discontinued IFN beta therapy

Courtesy Merck Serono


What is needed?What is needed?

Patient education Patient education – about the diseaseabout the disease

ongoing but subclinical diseaseongoing but subclinical disease no marker for disease activityno marker for disease activity

– about the treatments about the treatments are partially effective are partially effective patients must have realistic expectation patients must have realistic expectation make patients feel worse, not better make patients feel worse, not better occurrence of a relapse is expected but occurrence of a relapse is expected but

undermines patient’s confidence in the undermines patient’s confidence in the treatment treatment


What more is needed?What more is needed?

Treatments with improved tolerability Treatments with improved tolerability and safetyand safety– IFNIFNββ and GA and GA

have good safety profilehave good safety profile have not so good tolerabilityhave not so good tolerability

– natalizumab (and mitoxantrone off-label) natalizumab (and mitoxantrone off-label) have good tolerabilityhave good tolerability have not so good safety profile have not so good safety profile

– oral agents and other new agentsoral agents and other new agents safety is perhaps going to be a concern based safety is perhaps going to be a concern based

on the mechanism of action of some on the mechanism of action of some


What is really needed?What is really needed?

Treatments with improved Treatments with improved efficacy efficacy – agents that agents that stopstop relapses and relapses and

progression progression including agents for SPMS and PPMSincluding agents for SPMS and PPMS

– agents that are neuroprotective and agents that are neuroprotective and reversereverse the disease process the disease process

– agents that areagents that are curative! curative!


End

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