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
M Sandberg 2008-11-13M Sandberg 2008-11-13
Why are patients Why are patients with MS not with MS not compliant?compliant?
M Sandberg 2008-11-13M Sandberg 2008-11-13
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?
M Sandberg 2008-11-13M Sandberg 2008-11-13
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
M Sandberg 2008-11-13M Sandberg 2008-11-13
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
M Sandberg 2008-11-13M Sandberg 2008-11-13
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%
M Sandberg 2008-11-13M Sandberg 2008-11-13
‘‘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
M Sandberg 2008-11-13M Sandberg 2008-11-13
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
M Sandberg 2008-11-13M Sandberg 2008-11-13
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
M Sandberg 2008-11-13M Sandberg 2008-11-13
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
M Sandberg 2008-11-13M Sandberg 2008-11-13
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
Nu
mb
er
of
cas
es
(m
illi
on
)
An
xie
ty d
iso
rde
rs
Mig
rain
e
Aff
ec
tive
dis
ord
ers
Ad
dic
tio
n
Dem
en
tia
Psy
ch
oti
c d
iso
rder
s
Ep
ile
ps
y
Par
kin
son
's d
ise
as
e
Str
ok
e
Tra
um
a
Mu
ltip
le S
cle
ros
is
Bra
in t
um
ou
r
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
ou
r
mu
ltip
le s
cler
osi
s
stro
ke
dem
enti
a
psy
cho
tic
dis
ord
ers
par
kin
son
epile
psy
affe
ctiv
e d
iso
der
s
trau
ma
add
icti
on
anxi
ety
dis
ord
ers
mig
rain
e
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
M Sandberg 2008-11-13M Sandberg 2008-11-13
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)
M Sandberg 2008-11-13M Sandberg 2008-11-13
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
M Sandberg 2008-11-13M Sandberg 2008-11-13
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
M Sandberg 2008-11-13M Sandberg 2008-11-13
What happens in clinical What happens in clinical practice?practice?
M Sandberg 2008-11-13M Sandberg 2008-11-13
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
M Sandberg 2008-11-13M Sandberg 2008-11-13
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
M Sandberg 2008-11-13M Sandberg 2008-11-13
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
M Sandberg 2008-11-13M Sandberg 2008-11-13
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!
M Sandberg 2008-11-13M Sandberg 2008-11-13
End