Thank you for joining. The webinar will begin shortly This webinar - PowerPoint PPT Presentation

Thank you for joining. The webinar will begin shortly This webinar is organised and funded by Teva Pharmaceuticals Europe B.V. Date of Preparation: December 2018 | HQ/MTCNS/18/0009a

This webinar is organised and funded by Teva Pharmaceuticals Europe B.V. Date of Preparation: November 2018 | HQ/MTCNS/18/0009a

Welcome and Introduction Prof. Sven Schippling

Faculty Prof. Sven Schippling, Moderator Deputy Head of the Department of Neuroimmunology and Clinical Multiple Sclerosis Research (nims) at the University Hospital Zürich, Switzerland Prof. Gavin Giovannoni Chair of Neurology, Blizard Institute, Barts and The London School of Medicine and Dentistry, UK

Agenda Time (CET) Title Speaker 11:00–11:05 Welcome and introduction Sven Schippling 11:05–11:10 Understanding EDSS Sven Schippling 11:10–11:20 EDSS: Is it fit for purpose? Gavin Giovannoni 11:20–11:25 Ask the audience All 11:25–11:30 Beyond EDSS: How else can we evaluate disability progression? Sven Schippling 11:30–11:40 Exploring other clinical measures of disability: A discussion Gavin Giovannoni 11:40–11:45 Ask the audience All 11:45–11:55 How best to assess disability progression in everyday life? Patient contributor A patient’s perspective 11:55–12:00 Future perspectives Sven Schippling

? ? ? Join the discussion • There will be opportunity to ask questions throughout the webinar • Join the discussion during the Ask the Audience interactive sessions Participating is easy: 1. Take your mobile device 2. Go to www.sli.do 3. Enter the event code: #msmatters

Technical support • If you experience any technical problems during the webinar please get in touch: § Call our support team: +31(0)79 202 0001 § Email us at: support@republic-m.com

Understanding EDSS Prof. Sven Schippling

Disclosures • Sven Schippling is supported by the Swiss National Science Foundation (SNF), the Swiss Multiple Sclerosis Society, the Betty and David Koetser Foundation for Brain Research and the Myelin Repair Foundation (USA). • He is the Co-Director of the Clinical Research Priority Program for Multiple Sclerosis (CRPP MS ) supported by the University of Zurich. • He is a member of the International Clinical Consortium of the Guthy Jacksson NMO Charitable Foundation, California, USA. • He sits on the Steering committees of the OCTIMS, PASSOS, BENEFIT, REFINE, EMPIRE, ENSEMBLE and CLARIFY- MS trials, the MS in the 21 st Century and the ParadigMS initiatives. • He is a founding member of the Neuromyelitis Optica Study Group (NEMOS), Germany, and the Drug Development Network (DDNZ), Zurich, Switzerland. • He received travel support as well as speaker ´ s fees from Actelion, Almirall, Bayer Healthcare, Biogen, Sanofi/Genzyme, Merck, Novartis, Roche, Santen, TEVA.

A consequence of increasing disability in MS: Early loss of employment 1 Results based on a survey • Austria sent to 13,186 patients in Belgium 90 9 countries Germany ≤ 65 years of age working (%) 80 Italy Proportion of patients • The proportion of patients 70 Netherlands employed or on long-term Spain 60 Sweden sick leave is calculated as a 50 Switzerland percentage of patients 40 UK 65 years of age or younger 30 ~10 years 2 20 In a Danish cohort study, the • median time to early pension 10 was 10 years for patients and 0 24 years for controls 2 0.0/1.0 2.0 3.0 4.0 5.0 6.0 6.5 7.0 8.0/9.0 EDSS score EDSS=Expanded Disability Status Scale Adapted from 1. Kobelt G, et al. J Neurol Neurosurg Psych 2006;77:918–26; 2. Pfleger CC, et al. Mult Scler. 2010;16:878–82.

What is EDSS? Pyramidal • Method of quantifying and monitoring disability in MS over time Other Cerebellar • The EDSS scale ranges from 0–10 in EDSS 0.5 unit increments Cerebral functional • EDSS 1.0–4.5 refers to people with MS Brainstem function who are able to walk without any aid and systems is based on measures of impairment in 8 functional systems Visual Sensory function • EDSS steps 5.0–9.5 are defined by the Bowel and impairment to walking bladder function Adapted from https://www.mstrust.org.uk/a-z/expanded-disability-status-scale-edss; Accessed November 2018.

The Expanded Disability Status Scale (EDSS) EDSS Restricted to bed or chair Assistance required to Relatively Death walk severe disability Normal Restricted to Confined neurological Disability Minimal a wheelchair to bed examination precludes full disability daily activities Moderate disability No disability 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 Adapted from Kurtzke JF. Neurology 1983;33:1444–52.

EDSS: Is it fit for purpose? Prof. Gavin Giovannoni

Disclosures • In the last 5 years, Gavin Giovannoni has received compensation for serving as a consultant or speaker for, or has received research support from: • AbbVie, Actelion, Atara Bio, Biogen, Canbex, Celgene, Sanofi-Genzyme, Genentech, GlaxoSmithKline, Merck-Serono, Novartis, Roche, Synthon BV and Teva

? ? ? What is your experience of using EDSS? EDSS: Is it fit for What do your patients What are the think of the EDSS? purpose? strengths of EDSS? Are there any challenges What are the associated with performing weaknesses of EDSS? EDSS in the clinic?

Beyond EDSS: How else can we evaluate disease progression? Prof. Sven Schippling

Importance of bodily functions as rated by patients with MS Adapted from Heesen C, et al. Multiple Sclerosis 2008;14:988–91.

Optical coherence tomography Optical coherence tomography Detector Retina same (OCT) allows: Semitransparent distance as mirror #2 mirror splits light beam Infrared light • Rapid, non-invasive quantification 800nm wavelengths Detector of retinal nerve fibre layer Mirror #2 thickness and macular volume by A Transmitted light low coherent near infrared light • In vivo imaging of the retinal Infrared light 800nm wavelengths pathology B Reflected light Mirror #2 Adapted from Frohman EM, et al. Nat Clin Pract Neurol. 2008;4:664–75.

OCT findings in MS patients with a history of optic neuritis Significant difference between the groups ***: p<0.001 HC=healthy control RRMS=relapsing-remitting MS SPMS=secondary progressive MS ON=optic neuritis Adapted from Oberwahrenbrock T, et al. Mult Scler Int. 2012;2012:530305.

OCT findings in MS patients without a history of optic neuritis Significant difference between the groups: * p<0.05; **p<0.01;***p<0.001 HC=healthy control RRMS=relapsing-remitting MS SPMS=secondary progressive MS PPMS=primary progressive MS NON=No optic neuritis Adapted from Oberwahrenbrock T, et al. Mult Scler Int. 2012;2012:530305.

Structural retinal, functional visual damage and visual QoL 100 80 Macular RNFL r=0.31, P=0.0006 GCL+IPL OPL+INL 60 OPL+PRL r=0.49, P<0.0001 40 Photo courtesy of James 20 Fujimoto, PhD 0 60 70 80 90 100 Thickness of GCL+IPL (microns) NEI-VFQ-25 composite (best QoL=100 points) Low-contrast 2.5% (number of letters identified correctly) 95% confidence interval from SE of Prediction for fitted line Walter SD, et al. Ophthalmology 2012; Brandt AU et al. Akt Neurologie 2017

Retinal thickness is associated with worsening of MS 100 Lowest vs highest tertile HR=1.65, 95% CI 1.23-2.21, p=0.001 Intermediate vs highest tertile HR=1.00, 95% CI 0.72-1.38, p=0.982 • Patients with a pRNFL of pRNFL thickness 80 ≤87 μm (Spectralis) or Lowest Intermediate ≤88 μm (Cirrus) had double Cumulative % Highest 60 the risk of disability worsening at any time after 40 the first and up to the 3 rd year of follow up 20 • Risk increased almost four times after the 3 rd year and 0 up to the 5 th year of follow 0 1 2 3 4 5 Follow-up (years) up Number at risk Lowest pRNFL 297 278 175 89 29 15 Intermediate pRNFL 290 268 179 96 35 22 Highes pRNFL 292 272 206 123 45 24 pRNFL=peripapillary Adapted from Martinez-Lapiscina EH, et al. Lancet Neurol. 2016;15:574–84.

How ‘benign’ is benign MS? Benign MS: Cognitive psychological and social aspects in a clinical cohort • 163 patients with ‘benign’ MS (disease duration ≥15 years and EDSS score ≤3.0): – Cognitive impairment 45% – Fatigue 49% – Depression 54% Amato MP, et al. J Neurol. 2006;253:1054–9.

The hidden symptoms of MS: Cognitive functioning in clinically isolated syndrome • Deficits were found ≥ 2 cognitive tests (%) mainly in memory, Patients failing speed of information processing, attention and executive functions p<0.0001 Adapted from Feuillet L, et al. Mult Scler. 2007;13:124–7.

Cognitive impairment and grey matter volumes Cognitive parameters: • Memory task • Information processing speed • Attention • Verbal fluency NCV=normalised neocortical grey matter volume Adapted from Calabrese M, et al. Arch Neurol. 2009;66:1144–50.

Exploring other clinical measures of disability: A discussion Prof. Gavin Giovannoni

? ? ? EDSS vs MSFC Mobility tests Visual acuity tests (timed 25 foot walk) Disability assessment Tests in clinical practice vs Coordination tests, clinical trials e.g. 9-hole peg test Smart phone tests Cognitive testing

How best to assess disability progression in everyday life? A patient’s perspective Krish Chohan