Post on 14-Dec-2014
description
Both teriflunomide and alemtuzumab are investigational treatments in phase III development. They are not approved by FDA nor EMA for use in MS
Clinical implications: the potential of tailored MS treatment
Gavin Giovannoni
Blizard Institute of Cell and Molecular Science Barts and The London School of Medicine and Dentistry Queen Mary
University of London, UK
Disclosures
• This is presentation is part of a Genzyme sponsored symprosium
• Research support received from: Bayer-Schering Healthcare, Biogen-Idec, Merck Serono, Merz, Novartis, sanofi-aventis and Teva
• Personal compensation received for serving as a grant reviewer, from the Irish Science Foundation
• Personal compensation received for participating on advisory boards in relation to clinical trial design, trial steering committees and data and safety monitoring committees for: Bayer-Schering Healthcare, Biogen-Idec, Elan, Fiveprime, Genzyme, GlaxoSmithKline, GW Pharma, Ironwood, Merck Serono, Novartis, Roche, sanofi-aventis, Synthon BV, Teva, UCB Pharma and Vertex Pharmaceuticals
• Investigator, CARE-MS I and II studies
The views expressed in the following slide sets are those of the individual authors and do not necessarily reflect the views of sanofi-aventis or Genzyme
Primary Care Referral Diagnosis Minimalimpairment
Moderateimpairment
Severeimpairment
End oflife care
Prevention
Cognition
Depression
Fatigue
Bladder
Bowel
Sexual dysfunction Tremor
Pain
Swallowing
Spasticity
Falls
Balance problems
Insomnia
Restless legs
Studying
Employment
RelapsesDMTs
Fertility
Rehab
Suprapubiccatheter
ITB
Palliative Care
PhysioST
OTCNS
Counselling
Radiology
Neurophysiology
Clinical trials
Gait
A ‘holistic’ approach to MS
Theoretical model: treat early and aggressively and you prevent disability
Natural course of disease
Laterintervention
Latertreatment
Treatmentat diagnosis Intervention
at diagnosis
Time
Disease Onset
Dis
abili
ty
Who discusses mortality with their patients?
Primary Care Referral Diagnosis Minimalimpairment
Moderateimpairment
Severeimpairment
End oflife care
Prevention
Cognition
Depression
Fatigue
Bladder
Bowel
Sexual dysfunction Tremor
Pain
Swallowing
Spasticity
Falls
Balance problems
Insomnia
Restless legs
Studying
Employment
RelapsesDMTs
Fertility
Rehab
Suprapubiccatheter
ITB
Palliative Care
PhysioST
OTCNS
Counselling
Radiology
Neurophysiology
Clinical trials
Gait
A ‘holistic’ approach to MS
Survival in MSers is shortened by 8 to 12 yearsSurvival Probability of Norwegian Patients with RRMS
(Hordaland County, Western Norway, 1953–2003)
RRMS=relapsing-remitting MS.Adapted from Torkildsen NG et al. Mult Scler. 2008;14:1191-1198.
500 5 10 15 20 25 30 35 40 450
10
20
30
40
50
60
70
80
90
100
Surv
ival
(%)
Years After Onset
30 35 40 45 50 55 60 65 70 75 80Approximate Patient Age
General PopulationRRMS95% CI
The survival disadvantage in MS is greater than in other chronic diseases
Standardized Mortality Ratios in Chronic Diseases
Disease SMR (range)
Cardiovascular disease1* 1.34 (1.23–1.44)
Ischemic stroke2† 1.75(1.38–2.19)
Early breast cancer3 2.0 (1.6–2.7)
Crohn’s disease4 2.8
MS5 2.8 (2.6–3.1)
MS (2–9.9 years after diagnosis)5 2.4 (1.9–2.9)
MS (≥10 years after diagnosis)5 3.1 (2.8–3.4)
Parkinson’s disease6 3.66 (3.37–3.95)
Type 2 diabetes1 4.47 (3.91–5.10)
*In patients with type 2 diabetes; †in patients with valvular heart disease in Olmsted County, Minnesota.1. De Marco R et al. Diabetes Care. 1999;22:756-761; 2. Petty DW et al. Mayo Clin Proc. 2005;80:1001-1008; 3. Hooning MJ et al. Int J Radiat Oncol Biol Phys. 2006;64:1081-1091; 4. South East England Public Health Observatory, Mortality trends. 2006; 5. Sumelahti ML et al. Mult Scler. 2010;16:1437-1442; 6. Hristova DR. Folia Medica. 2009;51:40-45.
21-year long-term follow-up of IFNb-1b studytime from study randomization to death
Early treatment (3 years) with IFNb-1b was associated with a 47% reduction in the risk of dying over 21 years compared with initial placebo treatment
Source: Poster Goodin et al. Neurology. 2012 Apr 24;78(17):1315-22.
At risk:IFNB-1b 250 µgPlacebo
124123
124120
121117
118109
10488
HR=0.532 (95% CI: 0.314–0.902)46.8% reduction in hazard ratio Log rank, P=0.0173
IFNB-1b 250 µg
Placebo
0 2 4 6 8 10 12 14 16 18 20 2265%
70%
75%
80%
85%
90%
95%
100%
Time (Years)
Pro
po
rtio
n o
f p
ati
en
ts w
ho
are
sti
ll a
live
Who discusses employment with their patients?
Primary Care Referral Diagnosis Minimalimpairment
Moderateimpairment
Severeimpairment
End oflife care
Prevention
Cognition
Depression
Fatigue
Bladder
Bowel
Sexual dysfunction Tremor
Pain
Swallowing
Spasticity
Falls
Balance problems
Insomnia
Restless legs
Studying
Employment
RelapsesDMTs
Fertility
Rehab
Suprapubiccatheter
ITB
Palliative Care
PhysioST
OTCNS
Counselling
Radiology
Neurophysiology
Clinical trials
Gait
A ‘holistic’ approach to MS
Unemployment
Pfleger et al. Mult Scler. 2010;16:121-126.
0 5 10 15 20 25
Time (years)
0
0.2
0.4
0.6
0.8
1.0
Prob
abili
ty
Control PersonsMS Patients
Probability of Remaining in Active Employment After Onset of MS
Who discusses relationships with their patients?
Primary Care Referral Diagnosis Minimalimpairment
Moderateimpairment
Severeimpairment
End oflife care
Prevention
Cognition
Depression
Fatigue
Bladder
Bowel
Sexual dysfunction Tremor
Pain
Swallowing
Spasticity
Falls
Balance problems
Insomnia
Restless legs
Studying
Employment
RelapsesDMTs
Fertility
Rehab
Suprapubiccatheter
ITB
Palliative Care
PhysioST
OTCNS
Counselling
Radiology
Neurophysiology
Clinical trials
Gait
A ‘holistic’ approach to MS
Divorce and separation
*Life table method.Pfleger et al. Mult Scler. 2010; 16:121-126.
0 5 10 15 20 25
Time to Event or End of Observation (years)
0
0.2
0.4
0.6
0.8
1.0
Prob
abili
ty
Population ControlsMSers
Crude probability of remaining in a relationship after onset of MS*
Who discusses QoL with their patients?
The effect of MS on Quality of Life
• MS is one of the most common causes of neurological disability in young adults2
• Natural history studies indicate that it takes a median time of 8, 20, and 30 years to reach the irreversible disability levels of EDSS scores 4.0, 6.0, and 7.0, respectively3
*Utility measures are derived from EQ-5D using the EuroQoL instrument; †error bars depict 95% CIs. Half points on EDSSare not shown on graph axis, except at EDSS score 6.5.EDSS=Expanded Disability Status Scale; EQ-5D=European Quality of Life-5 Dimensions; QoL=quality of life.1. Adapted from Orme M et al. Value In Health. 2007;10:54-60; 2. WHO and MS International Foundation (MSIF). http://apps.who.int/bookorders/anglais/detart1.jsp?sesslan=1&codlan=1 &codcol=15&codcch=747. Accessed March 6, 2012;3. Confavreaux C et al. Brain 2003; 176:770-782. 4. Compston A, Coles A. Lancet. 2008;372:1502-1517.
Util
ity
EDSS and Utility* Show a Significant Inverse Relationship1†
Util
ity
EDSS Status
0.0 1.0 2.0 3.0 4.0 5.0 6.0 6.5 7.0 8.0 9.0–0.4–0.3–0.2–0.1
00.10.20.30.40.50.60.70.80.9
Who of you routinely measures blood vitamin D levels in people with MS?
Primary Care Referral Diagnosis Minimalimpairment
Moderateimpairment
Severeimpairment
End oflife care
Prevention
Cognition
Depression
Fatigue
Bladder
Bowel
Sexual dysfunction Tremor
Pain
Swallowing
Spasticity
Falls
Balance problems
Insomnia
Restless legs
Studying
Employment
RelapsesDMTs
Fertility
Rehab
Suprapubiccatheter
ITB
Palliative Care
PhysioST
OTCNS
Counselling
Radiology
Neurophysiology
Clinical trials
Gait
A ‘holistic’ approach to MS
Fracture risk in multiple sclerosis
Dobson et al. Submitted 2012.
Osteoporosis in multiple sclerosis
Dobson et al. Submitted 2012.
Treatment Strategy
DMT, disease-modifying therapies; EDSS, Expanded Disability Status Scale.1 Adapted from Compston A et al. Lancet 2008;372:1502–17; 2 O’Connor P et al. Lancet Neurol 2009;8:899–897
The natural course of relapsing-remitting MS1
MRI Events
Secondary progressiveFirst
clinicalevent
Time (years)
Relapsing-remitting
Pre-clinical
Inflammation
Disability
Brain volume
Axonal loss
Dis
ease
Sev
erity
Despite treatment, approximately one quarter (21–27%) of patients worsened by ≥1 point on the EDSS within 2 years2
Despite DMT, disease often continues to progress
Who monitors prognostic factors of a treatment response to DMTs?
Primary Care Referral Diagnosis Minimalimpairment
Moderateimpairment
Severeimpairment
End oflife care
Prevention
Cognition
Depression
Fatigue
Bladder
Bowel
Sexual dysfunction Tremor
Pain
Swallowing
Spasticity
Falls
Balance problems
Insomnia
Restless legs
Studying
Employment
RelapsesDMTs
Fertility
Rehab
Suprapubiccatheter
ITB
Palliative Care
PhysioST
OTCNS
Counselling
Radiology
Neurophysiology
Clinical trials
Gait
A ‘holistic’ approach to MS
Breakthrough disease after treatment initiation
Patients with breakthrough disease can be identified with• Clinical measures
– Relapses– EDSS progression
• MRI measures– T2 and Gd+ lesions
• Biological markers– IFNβ NAbs/lack of MxA gene induction– Natalizumab antibodies
Gd+=gadolinium-enhancing; IFNβ=interferon beta; NAbs=neutralizing antibodies; Abs=antibodies; MxA= myxovirus protein A.
Relapse on IFNβ therapy increases risk of sustained disability progression
• Risk is not much greater for 2 relapses or more• Sensitivity is only 50%
HR=hazard ratio; SE=standard error.Bosca et al. Mult Scler. 2008;14:636-639.
HR SE P Value 95% CI
No relapses (reference=1) 1
One relapse 3.41 1.47 0.005 1.46–7.98
Two or more relapses 4.37 1.74 0.000 1.90–9.57
HR of EDSS Increase in Patients with No Relapses, 1 Relapse, and 2 or More Relapses During the First 2 Years of IFN Treatment
0 20 40 60 80
0
0.25
0.50
0.75
Analysis Time (Months)
No RelapsesOne RelapseTwo or More Relapses
1.00
EDSS
Pro
gres
sion
Surv
ival
Pro
babi
lity
Strongest predictor of disability progression on IFNβ therapy is progression itself
Disease Activity During 2 Years of Treatment and Prediction of Disability Progression* at 6 Years
GroupSensitivity (%)
(CI)Specificity (%)
(CI)
A. An increase of at least one EDSS step confirmed at 6 months 85 (64–95) 93 (86–97)
B. Occurrence of any relapse 80 (58–92) 51 (41–61)
C. Occurrence of two or more relapses 45 (26–66) 81 (72–82)
D. A decrease in relapse rate less than 30% compared with 2 years before therapy 40 (22–61) 86 (77–91)
E. A decrease in relapse rate less than 50% compared with 2 years before therapy 40 (–61) 81 (72–88)
F. No decrease or identical relapse rate compared with 2 years before therapy 35 (18–57) 88 (79–93)
G. Definition A or B 90 (70–97) 48 (38–58)
H. Definition A or E 85 (64–95) 76 (66–83)
I. Definition A and B 75 (53–89) 97 (91–99)
J. Definition A and E 40 (22–61) 99 (94–99)
*EDSS score ≥6.0 or increase in at least 3 EDSS steps.Río J et al. Ann Neurol. 2006;59:344-352.
Study or SubgroupOdds Ratio
IV, Random, 95% CIKinkel 2008
Prosperini 2009Total (95% CI) 9.86 (2.33, 41.70)
Dobson et al. Submitted 2012.
MRI to monitor treatment response toIFNβ: a systematic review
Study or SubgroupOdds Ratio
IV, Random, 95% CIKinkel 2008
Pozzilli 2005Prosperini 2009
Sormani 2011Total (95% CI) 2.69 (0.72, 10.04)
0.01 0.1 1 10 100Disease Less Likely Disease More Likely
One New T2 Lesion
Favors Experimental Favors Control1001010.10.01
Two or More New T2 Lesions
Study or SubgroupOdds Ratio
IV, Random, 95% CIKinkel 2008
Rio 2008
Total (95% CI) 5.46 (2.48, 12.04)
MRI to monitor treatment response toIFNβ: a systematic review
Dobson et al. Submitted 2012.
Study or SubgroupOdds Ratio
IV, Random, 95% CIKinkel 2008
Pozzilli 2005Tomassini 2006
Total (95% CI) 3.34 (1.36, 8.22)
0.01 0.1 1 10 100Disease Less Likely Disease More Likely
One New Gd+ Lesion
0.01 0.1 1 10 100
Disease Less Likely Disease More Likely
Two or More New Gd+ Lesions
Clinical importance of neutralising antibodies against IFN-beta on relapses
Sorensen et al. Lancet 2003; 362: 1184–91.
Mean change in EDSS
Malluci et al. Neurology 2004.
Predictors of long-term clinical response to interferon beta therapy in relapsing multiple sclerosis
Tomassini et al. J Neurol (2006) 253 : 287–293.
How to improve adherence to DMTs?
DMT, disease-modifying therapy; IFN, interferon; GA, glatiramer acetateGiovannoni & Waubant, MSJ 2012
Systematic review of DMTs: treatment discontinuation by study type
70
60
50
40
30
20
10
0
Patie
nts
disc
ontin
uing
trea
tmen
t (%
)
IFNβ-1a30 µg IM
q.w.(n=5898)
IFNβ-1a44 µg SC
t.i.w.(n=3446)
IFNβ-1b250 µg SC
e.o.d.(n=3942)
GA20 µg SC
o.d.(n=2855)
70
60
50
40
30
20
10
0
Patie
nts
disc
ontin
uing
trea
tmen
t (%
)
IFNβ-1a30 µg IM
q.w.(n=5836)
IFNβ-1a44 µg SC
t.i.w.(n=3124)
IFNβ-1b250 µg SC
e.o.d.(n=3482)
GA20 µg SC
o.d.(n=2628)
≤12 months13–24 months>24 months
Randomised controlled trialObservational study
• Treatment discontinuation was frequent in both randomised controlled trials and observational studies
• Up to 40% of patients discontinue treatment within the first 2 years
Studies included ranged from January 1993 – October 2008
Impact of IFN-β adherence on relapse rateRe
lativ
e ris
k of
rela
pse
N=1606, 2006−2008; *includes all licensed IFN-β drugs excluding Extavia®IFN, interferon; MPR, medication possession ratioSteinberg SC et al. Clin Drug Investig 2010;30:89–100
1.15
1.10
1.05
1.00
0.95
0.90
>85% <80% <75% <70% <65% <60%
4% of patients had MPR >85%, on average 72−76%
Medication possession ratio (MPR)
• Poor adherence to IFN-β* increases relapse rate and healthcare resource utilisation
Other
Pregnancy/planned pregnancy
Nobody available to administer
Not confident in treatment benefits
Financial reasons
Did not pick up medication
Dosing schedule difficult/inconvenient
Forgot to administer
Did not feel need for injection
Depression
Weakness
Skin reaction
Injection anxiety
Headache
Pain at injection site
Flu-like symptoms
Fatigue
Tired of taking injections
0 10 20 30 40 50 60
17
1
2
2
3
5
10
50
4
6
8
9
10
10
12
13
15
20
Patient factors
Injection/tolerability factors
Patients (%)
32% of patients: at least one injection-related reason
84% of patients: other various reasons
The Global Adherence Project (GAP): reasons for non-adherence
Patients may report more than one reason
Devonshire V et al. Eur J Neurol 2011;18:69–77
Other
N=2648
Who engages patients in the decision making process concerning their treatment?
Concordance modelCompliance model
Prescriber decides diagnosis and treatment
Prescriber’s task is to explain and instruct
Patient’s task is to comprehend
Successful outcome is compliance
Prescriber and patient negotiate diagnosis and treatment
Prescriber elicits, explains, persuades and accommodates
Patient explains, considers and accommodates
Successful outcome is a negotiated agreement
From Compliance to Concordance. Pharmaceutical Journal 1997;259:860–861
Moving from compliance to concordance requires a culture change
Considerations prior to tailoring individualised treatment
Patient’s own treatment goals
OtherPatient’s own risk/benefit
tolerance
Patient’s own disease profile /characteristics
Individualised treatment
Treatment strategy
(e.g. induction vs escalation)
Economic factors
Increasingly complex
environment
Patient’s prior adherence to monitoring or drug regimen
• Many considerations are specific to patients’ needs and need to be layered withphysician-specific factors (e.g. treatment strategies) and economic factors 44
The large majority of MS patients want to be more actively involved in decision making
• In MS, 79% of patients prefer taking an active role in decision making about their condition
*Includes informed choice and shared decision-makingHeesen C et al. J Neurol Sci 2007;259:109–17
Autonomous Active role* Professional as agent
Paternalistic0
20
40
60
80
100
120
140
Num
ber o
f pati
ents
Listening to patients’ needs
• Several resources available to help patients understand treatment options and to map disease progression on current treatment– One-to-one counselling– Expert patient programmes– Online resources– Smartphone app in development– Education on available therapies and their
benefit/risk profiles
www.slcmsr.net/public
www.patientslikeme.com; www.msdecisions.org.uk; www.slcmsr.net/public
Case scenarios
Case studies: high risk CIS (?)
CIS – high risk/RMS (McDonald positive under new criteria1)• 28-year-old woman• Married with a young child• Presented with numbness/
muscle weakness and nausea• Several T2 and Gd-enhancing
lesions on MRI• Has done considerable
web-based research into her condition and understands risks of disease-progression
CIS, clinically isolated syndrome; IFN, interferon; GA, glatiramer acetate; 1 Polman CH et al. Ann Neurol 2011;69:292–302†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
Case studies: high risk CIS (?)
CIS – high risk/RMS (McDonald positive under new criteria1)• 28-year-old woman• Married with a young child• Presented with numbness/
muscle weakness and nausea• Several T2 and Gd-enhancing
lesions on MRI• Has done considerable
web-based research into her condition and understands risks of disease-progression
Current (2012) therapy
IFN-β / GA
Possibly Fingolimod*
CIS, clinically isolated syndrome; IFN, interferon; GA, glatiramer acetate;* In countries with a 1st-line license 1 Polman CH et al. Ann Neurol 2011;69:292–302†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
IFN-β / GA
Possibly Fingolimod*
Case studies: high risk CIS (?)
CIS – high risk/RMS (McDonald positive under new criteria1)• 28-year-old woman• Married with a young child• Presented with numbness/
muscle weakness and nausea• Several T2 and Gd-enhancing
lesions on MRI• Has done considerable
web-based research into her condition and understands risks of disease-progression
Current (2012) therapy Future (2013) therapy
IFN-β / GAFingolimod
BG-12†
Teriflunomide†
Alemtuzumab†
CIS, clinically isolated syndrome; IFN, interferon; GA, glatiramer acetate; 1 Polman CH et al. Ann Neurol 2011;69:292–302†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
Case studies: Newly diagnosed RRMS
Newly diagnosed RRMS with extensive risk factors• 52-year-old
African-American man• Two attacks within
6 months• High BoD on MRI• EDSS 3.0• Recovery from attacks has
been poor with impact on motor function and some loss of bladder control
• JC virus antibody positive
BoD, burden of disease; EDSS, extended disability status scale; GA, glatiramer acetate**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
Case studies: Newly diagnosed RRMS
Newly diagnosed RRMS with extensive risk factors• 52-year-old
African-American man• Two attacks within
6 months• High BoD on MRI• EDSS 3.0• Recovery from attacks has
been poor with impact on motor function and some loss of bladder control
• JC virus antibody positive
Current (2012) therapy
High-dose IFN-β / GAFingolimod**Natalizumab
BoD, burden of disease; EDSS, extended disability status scale; GA, glatiramer acetate**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
Case studies: Newly diagnosed RRMS
Newly diagnosed RRMS with extensive risk factors• 52-year-old
African-American man• Two attacks within
6 months• High BoD on MRI• EDSS 3.0• Recovery from attacks has
been poor with impact on motor function and some loss of bladder control
• JC virus antibody positive
Current (2012) therapy Future (2013) therapy
High-dose IFN-β / GAFingolimod**Natalizumab
High-dose IFN-β / GABG-12†
Fingolimod†
Teriflunomide†
Natalizumab†
Alemtuzumab†
BoD, burden of disease; EDSS, extended disability status scale; GA, glatiramer acetate**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
RRMS – stable with poor adherence• 44-year-old woman• No relapses in past 2 years• No new lesions on MRI, but
evidence of increasing lesion volume
• Often forgets to administer injections “my disease is stable”
• Has experienced injection-site reactions in the past
Case studies: RRMS – stable with poor adherence
RRMS, relapsing remitting multiple sclerosis; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
RRMS – stable with poor adherence• 44-year-old woman• No relapses in past 2 years• No new lesions on MRI, but
evidence of increasing lesion volume
• Often forgets to administer injections “my disease is stable”
• Has experienced injection-site reactions in the past
Current (2012) therapy
IFN-β / GA + MS nurse supportFingolimod**
Case studies: RRMS – stable with poor adherence
RRMS, relapsing remitting multiple sclerosis; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
RRMS – stable with poor adherence• 44-year-old woman• No relapses in past 2 years• No new lesions on MRI, but
evidence of increasing lesion volume
• Often forgets to administer injections “my disease is stable”
• Has experienced injection-site reactions in the past
Current (2012) therapy Future (2013) therapy
IFN-β / GA + MS nurse supportFingolimod**
IFN-β / GA BG-12†
Fingolimod†
Teriflunomide†
Case studies: RRMS – stable with poor adherence
RRMS, relapsing remitting multiple sclerosis; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
Case studies: RRMS breakthrough disease
RRMS – breakthrough disease• 47-year-old woman• Active lifestyle and keen to
retain independence• Failed on one IFNβ• Diagnosed 3 years ago• Several relapses and marked
disability progression since diagnosis EDSS = 4.0
• On-going MRI disease activity• Has researched and accepts
benefit/ risk profiles of new treatments
EDSS, extended disability status scale; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
Case studies: RRMS breakthrough disease
RRMS – breakthrough disease• 47-year-old woman• Active lifestyle and keen to
retain independence• Failed on one IFNβ• Diagnosed 3 years ago• Several relapses and marked
disability progression since diagnosis EDSS = 4.0
• On-going MRI disease activity• Has researched and accepts
benefit/ risk profiles of new treatments
IFN-β / GA Fingolimod*Natalizumab
Current (2012) therapy
EDSS, extended disability status scale; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
Case studies: RRMS breakthrough disease
RRMS – breakthrough disease• 47-year-old woman• Active lifestyle and keen to
retain independence• Failed on one IFNβ• Diagnosed 3 years ago• Several relapses and marked
disability progression since diagnosis EDSS = 4.0
• On-going MRI disease activity• Has researched and accepts
benefit/ risk profiles of new treatments
IFN-β / GA Fingolimod*Natalizumab
Current (2012) therapy
IFN-β / GANatalizumab
BG-12†
Teriflunomide†
Fingolimod†
Alemtuzumab†
Future (2013) therapy
EDSS, extended disability status scale; GA, glatiramer acetate*Cladribine is approved in Australia and Russia only**Fingolimod licensed indications vary by region†Treatment options are illustrative and not comprehensive and are subject to regulatory approval in the relevant markets
Conclusions
Summary and conclusions
Both teriflunomide and alemtuzumab are investigational treatments in phase III development. They are not approved by FDA nor EMA for use in MS
• MS is a bad disease
• Prognostic factors
• Treatment response markers
• Current DMTs have not been able to halt disease progression and carry a burden of adherence partly linked to injections
• Teriflunomide , Alemtuzumab and other emerging agents help address these needs
• As the disease profile and treatment needs of each patient differs, different therapy profiles will be of value
• Risk factors and patient views and the addition of new drugs to the treatment armamentarium will increase individualised treatment