Gavin Giovannoni & David Bates

Active Benefit-Risk Evaluations

and Patient Discussions

1

• Professor Giovannoni has provided consultation to Bayer-

Schering Healthcare, Biogen-Idec, Genzyme,

GlaxoSmithKline, Merck-Serono, Novartis, Protein

Discovery Laboratories, Teva-Aventis, UCB Pharma.

Ironwood, Eisai, Vertex, Roche, Synthon, Canbex. He has

received grant support from Bayer-Schering Healthcare,

Biogen-Idec, Merck-Serono, Merz, Novartis, Teva-Aventis,

GW Pharma

• Professor Bates has provided consultation to Biogen Idec,

Genzyme, GlaxoSmithKline, Novartis, UCB Pharma. He

has received grant support from Biogen Idec, Genzyme,

GlaxoSmithKline, Novartis, UCB Pharma

Disclosures

2

Therapies Indicated for “Highly Active

Disease”

David Bates

3

• Use as a single DMT in highly active RRMS for the following

adult patient groups:

Natalizumab and Fingolimod Indications in EU

4

EMA=European Medicines Agency; RRMS=relapsing–remitting MS; Gd+=gadolinium-enhancing.

http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002202/human_med_001433.jsp&mid=WC0b01ac0

58001d124&murl=menus/medicines/medicines.jsp. Accessed November 8, 2011.

High disease activity despite treatment with IFNβ (normally ≥1 year of treatment)

≥1 relapse in the last year while on therapy, ≥9 T2-hyperintense lesions,

or ≥1 Gd+ lesion or a “nonresponder”, defined as patient with unchanged or increased

relapse rate or ongoing severe relapses, compared with the previous year

Rapidly evolving severe RRMS

≥2 disabling relapses in 1 year, ≥1 Gd+ lesion or significant increase in T2 lesion load

AFFIRM: Reduction in ARR and Risk of

Disability Progression with Natalizumab

5

Week

Polman CH et al. N Engl J Med. 2006;354:899-910; Polman CH et al. Presented at AAN; April 9–16, 2005; Miami, FL.

Placebo (n=315)

Natalizumab (n=627)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

AR

R (

95%

CI)

P<0.001

0.73

0.23

Years 0–2

68% reduction in

ARR vs placebo

Number of Patients at Risk

Placebo

Natalizumab

315 296 283 264 248 240 229 216 208 200

627 601 582 567 546 525 517 503 490 478

199

473

3-Month Sustained Disability Progression

29%

17%

0

0.1

0.2

0.3

0.4

0 12 24 36 48 60 72 84 96 108 120

Pro

po

rtio

n w

ith

Su

sta

ined

Pro

gre

ssio

n

HR=0.58

P<0.001

42%

Placebo

Natalizumab

*Results shown are for fingolimod 0.5 mg dose.

Kappos L et al. N Engl J Med. 2010;362:387-401.

FREEDOMS: Reduction in ARR and Risk of

Disability Progression with Natalizumab

6

Number of Patients at Risk

Placebo

Fingolimod

418 391 371 341 320 308 290 279 143

425 416 388 370 354 340 332 321 152

HR=0.70

P=0.024

30%

54% reduction in

ARR vs placebo

0

0.1

0.2

0.3

0.4

Pro

po

rtio

n w

ith

Su

sta

ined

Pro

gre

ssio

n

P<0.001

0.40

0.18

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

AR

R (

95%

CI)

Years 0–2

Placebo (n=418)

Fingolimod* (n=425) 3-Month Sustained Disability Progression

Placebo

Fingolimod

Days

0 90 180 270 360 450 540 630 720

AFFIRM: Patients with Highly Active MS

(>2 Relapses and Gd+ Lesions at Baseline)

7

ARR Reduction*

Reduction in Risk of 12-Week

(3-Month) Sustained EDSS Progression†

Red

ucti

on

(%

)

53

(P=0.029)

81

(P<0.001)

*Natalizumab ARR reduction vs placebo: 0.28 vs 1.46; †EDSS progression calculated from 1–HR, 1–0.47 for natalizumab.

Tysabri [summary of product characteristics]; Hutchinson M et al. J Neurol. 2009;254:405-415 & 1035-1037.

Red

ucti

on

(%

)

FREEDOMS: Patients with Highly Active MS

(>2 Relapses and Gd+ Lesions at Baseline)

0

20

40

60

80

100

Fingolimodvs Placebo

(n=140)

0

20

40

60

80

100

Fingolimodvs Placebo

(n=140)

22

(P=0.521)

63

(P<0.001)

*Fingolimod ARR reduction calculated from 1–negative binomial regression rate ratio (1–0.37); †EDSS progression calculated from 1–HR, 1–0.78 for fingolimod.

Fingolimod EPAR Gilenya Assessment report EMA/108602/2011.

Red

ucti

on

(%

)

ARR Reduction*

Reduction in Risk of 12-Week

(3-Month) Sustained EDSS Progression†

Red

ucti

on

(%

)

8

AFFIRM: Natalizumab Increases the Proportion of

Patients Free of Clinical and MRI Disease Activity

Patients with No

Disease Activity over 2 Years

Placebo (n=304) 7% P<0.0001

Natalizumab (n=600) 37%

P<0.0001, natalizumab vs placebo, for all individual and combined disease measures.

MRI=magnetic resonance imaging; Gd+=gadolinium-enhancing.

Havrdová E et al. Lancet Neurol. 2009;8:254-260.

64%

Free of Clinical

Disease Activity

58%

Free of MRI

Disease Activity

58%

Free of

T2 Lesions

95%

Free of

Gd+ Lesions

84%

Free of

Progression

37%

Free of

Disease

Activity

71%

Free of

Relapses

9

7.2

15.4 13.0

36.7

46.7

68.4

0

10

20

30

40

50

60

70

80

Year 0-2 Year 0-1 Year 1-2

Patients

without

com

bin

ed

dis

ease a

ctivity (

%)

Placebo Natalizumab

AFFIRM: Proportion of Patients Without Disease

Activity* Increases from Year 1 to Year 2

*Absence of disease activity on the composite of clinical and radiological measures was defined as no relapse, no progression

of disability (sustained for 12 weeks), no gadolinium-enhancing lesions, and no new or enlarging T2-hyperintense lesions.

Harvrdova E at al. Lancet Neurol. 2009;8:254-260.

p<0.0001 for all comparisons

n=304 n=600 n=305 n=604 n=284 n=544

10

AFFIRM: Natalizumab Provided More Patients with

Freedom from Disease Activity

11

Pati

en

ts F

ree o

f

Dis

ease

Acti

vit

y (

%)

n=59

Overall Population

P<0.0001

Highly Active Patients*

P<0.0001

7.2

1.7

36.7

27.4

0

10

20

30

40

50 Placebo

Natalizumab

n=304 n=600 n=146

Post hoc analysis of AFFIRM; natalizumab vs placebo for both overall population and patients with highly active disease.

*Patients with ≥2 relapses in prior year and ≥1 Gd+ lesion at baseline.

Havrdová E et al. Lancet Neurol. 2009;8:254-260.

Havrdova et al., Lancet Neurol. 2009, 8:254-60.

*Highly active disease was defined as at least two relapses in the year before study entry and at least one gadolinium-enhancing lesion at

study entry; non-highly active disease was defined as fewer than two relapses or no lesions at study entry.

AFFIRM: Freedom from Disease Activity in

Highly Active and Non-highly Active Patients

3% 4%

34%

65%

0%

20%

40%

60%

80%

100%

Year 1 Year 2

n=59 n=56 n=137 n=146

Pa

tie

nts

Dis

ea

se

Ac

tivit

y F

ree

(%

)

18%15%

51%

70%

0%

20%

40%

60%

80%

100%

Year 1 Year 2

P<0.0001

P<0.0001

P<0.0001

Placebo

Natalizumab

Highly active patients* Non-highly active patients*

P<0.0001

n=246 n=228 n=407 n=458 P

ati

en

ts D

ise

as

e A

cti

vit

y F

ree

(%

)

12

FREEDOMS: Proportion of Patients

Disease Activity Free

13 13 12

3335

29

0

10

20

30

40

Overall Treatment-Naïve Previously Treated

Pa

tie

nts

(%

)

Placebo Fingolimod 0.5 mg

Kappos L et al. Presented at AAN; April 9–16, 2011; Honolulu, Hawaii. PD6.002.

13

AFFIRM: Brain Parenchymal Fraction (BPF)

*Change in BPF of natalizumab group at year 1 probably reflects “pseudoatrophy” from reduced edema/inflammation.

Miller DH. Neurology. 2007;68:1390-1401.

Placebo (n=315)

Natalizumab (n=627)

−1.0

−0.8

−0.6

−0.4

−0.2

0

Mean

Perc

en

tag

e C

han

ge i

n B

PF

−0.82

−0.80

P=0.822

vs placebo

Time (Years) 2 0 1

*

−0.39

−0.56

P=0.002

vs placebo

14

FREEDOMS: Brain Volume

*Change in brain volume vs placebo. Ranked ANCOVA adjusted for treatment group and baseline normalized volume.

Kappos L et al. N Engl J Med. 2010;362:387-401.

Placebo (n=383)

Fingolimod (n=395)

−1.0

−0.8

−0.6

−0.4

−0.2

0

Mean

Perc

en

tag

e C

han

ge

in B

rain

Vo

lum

e

−0.84

P<0.001

vs placebo

Time (Years) 2 0 1

* P=0.026

vs placebo

−1.2

−1.4

P=0.006

vs placebo *

*

15

Real-World Outcomes: Patients Failing

Treatment

Gavin Giovannoni

16

Real Life: Escalation to Natalizumab is More

Effective Than Switching Among GA/IFN

% Patients

2nd year*

Escalate to natalizumab n=106

Switch between GA/IFN n=161

Data from a post-marketing, prospective, observational study in 285 RRMS patients who failed treatment with IFNβ or GA therapy. After failure of

IFNβ or GA therapy patients were switched to either natalizumab (n=106) or IFNβ/GA (n=161); EDSS=Expanded Disability Status Scale;

GA=glatiramer acetate; IFNβ=interferon beta; MRI=magnetic resonance imaging; MS=multiple sclerosis; RRMS=relapsing remitting MS

*At 12 months there were no differences between the two groups in proportions of patients free from relapse, disability progression, MRI activity,

and combined activity.

Prosperini L et al. Mult Scler. 2012;18(1):64-71.

No EDSS

progression

No MRI activity Disease

activity free

p<0.0001

p=0.0003 p<0.0001

51

36

51

21

83

67 72

59

No relapses

p<0.0045

17

Natalizumab (TOP) Reduces Risk of Relapse

Compared to IFN and GA ( )

• Natalizumab treatment in TOP was associated with a significant reduction in risk of relapse, compared

with a prospective outcome registry of RRMS patients experiencing at least one relapse on treatment

IFN-GA (MS-COMET).

• In unmatched, unadjusted sample (left panel), risk of relapse was 1.68-fold (95% CI, 1.10–2.19-fold)

greater among MSCOMET compared to TOP MS patients despite a higher disease activity/severity

profile in the TOP cohort at baseline.

• In propensity matched sample (right panel), relapse risk in MSCOMET patients was increased 2.73-fold

(95% CI, 2.10–3.55-fold).

0.00

0.25

0.50

0.75

1.00

Pro

port

ion n

ot re

lap

sed

0 .5 1

Years since baseline

MSCOMET TOP

Unmatched, unadjusted

0.00

0.25

0.50

0.75

1.00

Pro

port

ion n

ot re

lap

sed

0 .5 1

Years since baseline

MSCOMET TOP

Propensity matched

Spelman T et al. Presented at ECTRIMS; October 10-13, 2012, New Orleans, LA. P303. IFN=interferon; GA=glatiramer acetate.

18

0.0

0.5

1.0

1.5

2.0

2.5

3.0

AFFIRM TOP Danish Switzerland/Germany

Switzerland France Belgium Italy TYSEDMUS

AR

R

Pre-Natalizumab

Natalizumab

Natalizumab: Low ARR Across Registries

and Independent Studies

19

*As of June 1, 2011, 3484 patients were enrolled. Overall in TOP, patients received a mean of 14.6 (±11.21) natalizumab infusions; 57% (n=1981)

of patients analyzed were followed for 1 year; 22% (n=761) were followed for 2 years; 7% (n=230) were followed for 3 years; †median. y=years;

mo=months; wk=weeks. 1. Polman C et al. N Engl J Med. 2006;354:899-910; 2. Hotermans C et al. Presented at WCN; November 12–17, 2011;

Marrakesh, Morocco; 3. Oturai A et al. Eur J Neurol. 2009;16:420-423; 4. Putzki N et al. Eur J Neurol. 2010;17:31-37; 5. Putzki N et al. Eur Neurol.

2010;63:101-106; 6. Outteryck O et al. J Neurol. 2010;257:207-211; 7. Belachew S et al. Eur J Neurol. 2011;18:240-245; 8. Sangalli F et al. Neurol Sci.

2010;31(suppl 3):299-302; 9. Vukusic S et al. Presented at ECTRIMS; October 19–22, 2011; Amsterdam, The Netherlands; P970.

n= 627 3484 234 97 85 384 45 285 456

Mean follow-up 2 y 14.6 mo* 11.3 mo† 1 y 1 y 1 y 44 wk 2 y 3 y

1 2 3

4

5 6 7 8 9

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

Switzerland/Germany

Switzerland France Belgium Sweden TYSEDMUS

EDSS

Sco

re (

me

an)

Pre-NatalizumabNatalizumab

Registries and Independent Studies:

Stable EDSS Scores

N 97 85 384 45 901† 2855 Mean follow-up 1 y 1 y 1 y 44 wk 2 y 3 y

EDSS=Expanded Disability Status Scale; RRMS=relapsing-remitting multiple sclerosis.

1. Putzki N et al. Eur J Neurol. 2010;17:31-37; 2rol. 2010;63:101-106; 3. Outteryck O et al. J Neurol. 2010;257:207-211;

4. Belachew S et al. Eur J Neurol. 2011;18:240-245; 5. Holmen C et al. Mult Scler. 2011;17:708-719; 6. Confavreux C et al. Presented at

EMA; May 3–6, 2011; London, England.

1

2 3 4 5 6

20

3.5 3.3 3.3 3.3

3.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

Baseline Year 1 Year 2 Year 3 Year 4

Me

an

ED

SS

Sc

ore

TOP: Mean EDSS Scores by Natalizumab

Treatment Duration

*Sustained (6-month) improvement was defined as a ≥1.0-point decrease in EDSS score from baseline; †sustained (6-month) progression was defined as a ≥1.0-point increase in EDSS score from baseline. EDSS=Expanded Disability Status Scale.

Pellegrini F et al. Presented at the 28th Congress of ECTRIMS, Lyon, France, Oct 10–13, 2012. P519.

n=4402 n=1839 n=1043 n=218 n=461

21

TOP: Clinically Disease Activity Free

89

65 59

0

20

40

60

80

100

Sustained progressionfree

Relapse free Clinical disease activity-free

Pro

po

rtio

n o

f p

atie

nts

(%

)

Sustained progression was defined as an increase of ≥1.0 point in the EDSS score sustained for 6 months; clinical disease

activity-free was defined as no relapses and no 24-week confirmed EDSS progression.

Pellegrini F et al. Presented at the 28th Congress of ECTRIMS, Lyon, France, Oct 10–13, 2012. P519.

22

Registries and Independent Studies and AFFIRM:

% Disease Activity Free on Natalizumab

Over 90% of AFFIRM patients were treatment naïve, and the remainder had been on a previous therapy for no more than 6

months, but not treated in the 6 months prior to enrolment. In contrast, approx 90% of patients in registries and independent

studies were switched to natalizumab after experiencing disease activity on a prior therapy.

*Relapse-free (freedom from progression not reported); EDSS worsening not determined in this analysis.

1. Belachew S et al. Eur J Neurol. 2011;18:240-245; 2. Putzki N et al. Eur J Neurol. 2010;17:31-37; 3. Fernandez O et al. J Neurol.

2012 Jan 31 [Epub ahead of print]; 4. Sangalli F et al. Neurol Sci. 2010;31(suppl 3):299-302; 5. Outteryck O et al. Presented at

ECTRIMS; October, 2011; Amsterdam, Netherlands; 6. Havrdová E et al. Lancet Neurol. 2009;8:254-260.

Cohort

Belgium1

(N=45)

Germany/

Switzerland2

(N=97)

Spain3

(N=825)

Italian4

(N=285)

French5

(N=603)

AFFIRM6

(N=942)

Follow-up 44 weeks 1 year 1 years 2 years 2 year 2 years

Freedom from

clinical disease

activity, %

82 63.9 -- 78* 45 64

Freedom from

radiologic disease

activity, %

71 64.9 94.6 69 68 58

Composite clinical

and radiological

freedom from

disease activity, %

62 48.5 63 63 49 37

23

Factors Predicting the Ultimate Goal of Disease

Activity Silencing

Havrdova E. et al. ECTRIMS Meeting poster 905, Gothenburg, Sweden 2010.

Havrdova E. et al. Neurology 2010 ;74:S3-7.

Variables Associated with Overall Freedom from Disease Activity (No Clinical or MRI Activity) over 2 Years in a Multivariate Logistic Regression Analysis

AFFIRM

Natalizumab-treated patients with fewer relapses, fewer MRI lesions, and lower EDSS scores at therapy initiation and who did not develop persistent anti-natalizumab antibodies were more likely to achieve freedom from disease activity over the course of the 2-year AFFIRM study.

24

Factors Predicting the Ultimate Goal of Disease

Activity Silencing

Prosperini L et al. J Neurol Sci. 2012;323:104-112.

Real-life

Stepwise logistic regression analysis showing the predictive variables for having a “full” response to natalizumab (i.e. no clinical and MRI activity) during a 24-month follow-up period.

Natalizumab appears to be more prone to induce a clinical and MRI remission of MS if started in patients with less aggressive disease (i.e. few relapses and mild disability)

25

Factors Predicting the Ultimate Goal of Disease Activity

Silencing

Relapses in prior 12

months

EDSS at

natalizumab start

Gd+ lesions at

baseline MRI scan

≤2 >2

Adj. P value <0.0001

<3.0 3.0–5.5

Adj. P value <0.001

>5.5

>2 ≤2

Adj. P value <0.0001

91.6%

disease

activity free

77.2%

disease

activity free

48.0% with

clinical activity

55.6% with

clinical activity

Patients with Clinical Activity

(poor responder)

Patients with MRI Activity

(partial responder)

Patients Free of Clinical and MRI Activity

(full responder)

26

Prosperini L et al. J Neurol Sci. 2012;323:104-112.

TOP: Earlier Natalizumab Treatment Favors ARR

Outcomes

P value was from the negative binomial model adjusted for gender, baseline relapse status (0 or 1 vs >1 relapse), EDSS score

(0.0–2.0, 2.5–4.0, and 4.5–9.5), disease duration (<8 vs ≥8 years), prior DMT use (0, 1, or >1), and treatment duration (<3 vs ≥3 years).

n=1836 n=2107

Baseline EDSS Score

Po

stb

aselin

e

Mean

An

nu

ali

zed

Rela

pse R

ate

P=0.0003

Number of Prior DMTs

n=366 n=1744 n=1866

P<0.0001

Kappos L et al. Presented at ENS; June 9–12, 2012; Prague, Czech Republic. O261.

TOP: Subgroup Analyses

27

TOP: Overall Stabilization of EDSS Scores in

Patients with Either a High or Low Starting EDSS

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

0 6 12 18 24 30 36 42 48

Med

ian

ED

SS

Sco

re

Time (months)

Kappos L et al. Presented at ENS; June 9–12, 2012; Prague, Czech Republic. O261.

28

Baseline EDSS Score ≤3.0 (n=1591)

Baseline EDSS Score >3.0 (n=1840)

Natalizumab should be used according to the SmPC

Natalizumab Effect on Neurofilament Light Levels

in Cerebrospinal Fluid of Patients with MS

29

NFL = Neurofilament light.

Gunnarsson M et al. Ann Neurol. 2011;69:83–89.

When to escalate the needed efficacy ?

Disease

progression

Escalating therapy/efficacy

• Persisting clinical/MRI activity

• Choice of second-line therapy

30

Disease

progression

Escalating therapy/efficacy

• Persisting clinical/MRI activity

• Choice of second-line therapy

When to escalate the needed efficacy ?

31

Risks

32

Balancing Benefits and Risks of Treatment

vs Risk of Poorly Controlled MS

33

Gilenya® (fingolimod) [summary of product characteristics]. East Hanover, NJ: Novartis Pharmaceuticals.

http://www.medicines.org.uk/EMC/medicine/24443/SPC/Gilenya+0.5mg+hard+capsules/. Accessed April 24, 2012

Tysabri® (natalizumab) [summary of product characteristics]. Dublin, Ireland: Biogen Idec; 2011.

http://www.medicines.org.uk/EMC/medicine/18447/SPC/TYSABRI+300+mg+concentrate+for+solution+for+infusion/. Accessed April 24, 2012.

Fingolimod Natalizumab

Risks

• PML

• Other CNS opportunistic infections

• Treatment during pregnancy if clinically required

• Hypersensitivity

• Other AEs per labelling

• Unknown long-term safety profile

Benefits

• Relapse rate

• Disability progression

• Freedom from disease activity

• Quality of life

• Brain atrophy (neuroprotective)

• Functional improvements

• Consistent effects in long-term real-life clinical use

• Well-defined safety profile and ability to stratify risk

Benefits

• Relapse rate

• Disability progression

• Freedom from disease activity

• Quality of life

• Brain atrophy (neuroprotective)

• Emerging safety profile and ability to de-risk cardiovascular issues

• Oral therapy

Risks

• Cardiovascular issues

• Macular edema

• Teratogenic potential

• Live vaccination contraindicated

• Other AEs per labelling

• Unknown long-term safety profile

Natalizumab PML risk stratification tool

Anti-JC virus antibody status

Negative Positive

Prior immunosuppressant use

Natalizumab treatment

>2 Years

Natalizumab treatment

>2 Years

No Yes

No Yes No Yes

Lowest Highest Relative PML Risk

< 1 in 10,000 1 in 94 1 in 256 1 in 668 1 in 1887

Mitoxantrone

Azathioprine

Methotrexate

Cyclophosphamide

Mycophenolate

Cladribine

Rituximab

Etc.

34

Treatment exposure time or prior IS use do not impact the risk estimates as long as the patient remains JCV Ab negative

Negative Anti-JCV

Antibody Status

PML Risk

≤0.07/1000*

Data beyond 4 years of treatment are limited. *Based on natalizumab exposure and 285 confirmed PML cases as of September 5, 2012. Prior IS data in overall natalizumab-treated patients based

on proportion of patients with IS use prior to natalizumab therapy in TYGRIS as of May 2011; and prior IS data in PML patients as of September 5,

2012. The analysis assumes that 55% of natalizumab-treated MS patients were anti-JCV antibody positive and that all PML patients test positive for

anti-JCV antibodies prior to the onset and diagnosis of PML. The estimate of PML incidence in anti-JCV antibody negative patients is based on the

assumption that all patients received at least 1 dose of natalizumab . Assuming that all patients received at least 18 doses of natalizumab , the estimate

of PML incidence in anti-JCV antibody negative patients was generally consistent (0.1/1000; 95% CI 0.00–0.62).

Biogen Idec, data on file.

35

Plavina et al., AAN Meeting 2013, San Diego, CA

S30.001 Longitudinal stability of anti-JC virus antibody status in multiple sclerosis patients: results of STRATIFY-1

Anti-JCV Antibody Status Over 18 Months

Pe

rce

nta

ge o

f b

as

eli

ne J

CV

an

tib

od

y n

eg

ati

ve

(%

)

36

STRATIFY-1: Longitudinal Serostability in Patients

Who Were Anti-JCV Antibody Negative at Baseline

Consistently high probability of staying all time-point negative based on three successive

6-monthly tests confirms longitudinal serostability of anti-JCV Ab negativity status

37

Plavina et al., AAN Meeting 2013, San Diego, CA

S30.001 Longitudinal stability of anti-JC virus antibody status in multiple sclerosis patients: results of STRATIFY-1

Putting MS in perspectives for your patient: Impact on

mortality, QoL, employment, and healthcare costs

38

Worsening

disability

SAEs

Remission

No

SAEs

IFN-GA

Natalizumab

Fingolimod

Mitoxantrone

Alemtuzumab*

Daclizumab*

Ocrelizumab*

Escalation

Risk/Risk and Benefit/Benefit considerations

Patient vs Physician

Risk

Benefit

Risk

Benefit

*Not currently licensed for treatment of MS.

• Patients and physicians should be equal partners in managing

MS

– Important for physicians to convey risks of MS and MS

therapy, but allow patients to make the ultimate decision

– Physicians should not project own perception of treatment

risks on patients

– This partnership may improve the long-term outcome of

patients with MS

Conclusions

40

http//www.peervoice.com/o1/pvr64. Accessed April 19, 2013.