Multiple Sclerosis : direct and indirect costs in Europe

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Multiple Sclerosis direct and indirect costs in
Europe

• Costs and quality of life of patients with
• Multiple Sclerosis in Europe
• Kobelt et al, JNNP, 2006 67 918-926
• N 13186 patients from 9 European countries
• The total mean annual costs per patient were
  estimated at
• 18000 euros for mild disease (EDSS lt 4)
• 36500 euros for moderate disease (EDSS 4-6,5)
• 62000 euros for severe disease (EDSS gt 7.0)
• The cost of a relapse was similar across the
  countries, ranging
• between 2800 euros and 4000 euros

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Multiple Sclerosis direct and indirect costs in
Belgium

• 2150 questionnaires from
• Cliniques Saint-Luc, UCL, Bruxelles
• Centre Neurologique et Réadaptation
  fonctionnelle, Fraiture
• MS and Revalidatiecentrum, Overpelt
• Elisabeth Ziekenhuis, Sijsele
• Response rate
• 38 or 799 patients, 68 female, mean age of
  48.1 years
• 14.5 of employed patients were on long-term
  sick leave (gt 3 months)
• 32.9 of patients had retired early due to MS

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Stability of the pathology
Treatment optimisation
Relapse / Disability
MRI activity
MRI Burden of disease
SPMS
Cerebral volume
Axonal loss
Preclinical
RRMS
Progression threshold
temps
Adapted from Goodkin. UCSF MS Curriculum. Jan
1999.
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The treatment of multiple sclerosis

• First line  ABCR 
• IFN-ß-1a IM qw - IFN-ß-1b od - IFN-ß-1a SC tiw
  - GA
• Second line Mitoxantrone - Natalizumab
• Third line Cyclophosphamide IV,
  methotrexate, Azathioprine ...

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Annual relapse rate in the pivotal studies(all
patients evaluated at 24 months)
2
Kappos 98
T0 before the studie PL Placebo
ITT analysis
1.72
1.5
1.5
1.48
1.28
1.27
1.2
1.17
1
0.91
0.91
0.9
0.87
0.84
0.65
IFN?-1b (1.6 MIU)
0.5
0.61
IFN?-1a
IFN?-1b (8 MIU)
IFN?-1a (22 ?g)
IFN?- 1a (44 ?g)
COP
T0
T0
PL
T0
PL
PL
T0
PL
0
(n338)
(n172)
(n560)
(n215)
IFN-ß-1b SC od
IFN-ß-1a IM qw
IFN-ß-1a SC tiw
GA
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Dose and Frequency are importantEVIDENCE - IRM
T2Active lesions / patient / MRIand Proportion
of active MRI/ patient
IFN-ß-1a SC tiw
1.5
1.4
IFN-ß-1a IM qw
p lt0.001 for all comparisons
0.9
1
Number Lesions Or Proportion
0.5
0.5
0.44
0.5
0.27
0
0
0
Active MRI
Active Lesions T2
Active MRI
Active Lesions T2
Adjusted Mean
Median
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Most patients treated with a DMD do not progress
80 of patients receiving DMD treatment did not
progress to SPMS1
70
58
60
50
50
40
Patients progressingto SPMS ()
30
20
20
10
0
PRISMS LTFU cohort(13.2 years after onset of
RRMS)
Natural historydataset 1
Natural historydataset 2
An incidence cohort, 10 years after the onset of
disease.2 A cross-sectional cohort of patients,
1115 years after onset of RRMS.3
1Kappos et al. Neurology 20066794453
2Weinshenker et al. Brain 198911213346
3Runmarker Anderson. Brain 199311611734.
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Decreasing the risk of poor adherence or
tolerability with DMD treatment

• Discontinuation rates of 1739 reported for
  patients with MS in first 35 years of
  disease-modifying drug therapy1,2
• Tolerability is critical for long-term treatment
  adherence
• Injection-site pain is a frequently reported
  local tissue side-effect associated with
  administration of sc IFN beta
• Discontinuation is potentially preventable by
  dose titration, patient education and concomitant
  therapy

1Tremlett Oger. Neurology 200361551554
2Mohr et al. Mult Scler 19962222226
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Tolerability injection-site reactions

• Improving the formulation to obtain a lower
  incidence of injection-site reactions (ISRs). New
  formulation compared to previous one in the
  EVIDENCE study

EVIDENCE, EVidence of Interferon Dose-response
European North American Comparative Efficacy
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Injection-site tolerability Evaluation of pain
In healthy volunteers

• Pain at injection similar to saline and much less
  than previous formulation

80
Maximum VAS scores
60
VAS score (mm)
40
20
0
New formulation
Previous formulation
Saline
Data from a double-blind, randomized,
(parallel-dose group), placebo-controlled study
to assess safety, tolerability, PK and PD of
single sc doses in healthy human
volunteers. Brearley et al. Int J Clin Pharmacol
Ther 20074530718.
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Future drugs in development

• ORAL
• Cladribine CLARITY (phase III)
• Fingolimod (FTY720) FREEDOMS, TRANSFORMS (phase
  III)
• Fumarate derivative DEFINE, CONFIRMS (phase
  III)
• Inosine ASIIMS (March 2008)
• Laquinimod (phase III)
• Teriflunomide (phase III)
• MONOCLONAL ANTIBODIES
• Alemtuzumab (ex-Campath anti-CD52 phase III)
• Daclizumab (anti-CD25 or anti-IL2 R a phase III)
• Rituximab (anti-CD20 phase III)
• Atacicept (anti-B cell receptor Taci phase II)
• The first three monoclonal antibodies are
  currently approved by the FDA for other
  indications (e.g. B-cell chronic lymphocytic
  leukemia)

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Multiple Sclerosis will be conquered when ...

• 1) it will be possible to completely stop the
  disease, in both aspects of acute inflammatory
  manifestations and silent background progression
  (progressive neurodegeneration)
• 2) it will be possible to protect the
  demyelinated neural fibers and to stimulate the
  remyelination of functional axons
• 3) it will be possible to detect persons at
  risk to develop the disease and to  vaccinate 
  them preventively