The invisible facets of MS and everyday challenges clinician s perspective. Mar Tintore

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1 The invisible facets of MS and everyday challenges clinician s perspective Mar Tintore Centre d Esclerosi Múltiple de Catalunya (Cemcat). Department of Neurology/Neuroimmunology Hospital Universitari Vall d Hebron Universitat Autònoma de Barcelona Barcelona

2 Disclosures M Tintoré has received compensation for consulting services and speaking honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Teva, Sanofi-Aventis, Novartis, Almirall and Roche.

3 MS diagnosis and prognosis CIS Will I develop further attacks? Will I develop disability? 3

4 CIS Translation to clinical practice Questions? Answers 4

5 Barcelona CIS cohort: Multivariate analysis at baseline Risk of conversion to CDMS Risk of reaching EDSS 3.0 ABCRE=Avonex, Betaseron, Rebif, Copaxone, Extavia (IFNβ/glatiramer acetate); HR=hazard ratio; OCB=oligoclonal bands. Tintoré M et al; Brain. 2015

6 Updated score for EDSS 3.0 High/ Very high baseline risk for EDSS NEW T2 NO/1-3 N=12 HR=15.0 (95%CI ) 1st year Treatment NO YES YES N=14 HR=5.2 (95%CI ) CDMS 12m NO NO N=24 HR=12.3 (95%CI ) 1st year Treatment YES N=24 HR=4.7 (95%CI ) N=15 YES HR=3.8 (95%CI ) CDMS 12m NO NO N=59 HR=7.4 (95%CI ) 1st year Treatment YES N=30 HR=4.4 (95%CI ) high/very high risk, 3+ new T2, CDMS Before 12m, No 1st year treat High/very high risk score Time to edss 0 12 Years from CIS 1 % edss free High/very high risk score % edss free Time to edss 0 12 Years from CIS high/very high risk, 3+ new T2, No CDMS Before 12m, No 1st year treat High/very high risk score Time to edss 0 12 Years from CIS high/very high risk, 3+ new T2, CDMS Before 12m, 1st year treat % edss free % edss free High/very high risk score 0 Time to edss 0 12 Years from CIS high/very high risk, No Or 1-3 new T2, CDMS Before 12m High/very high risk score Time to edss 0 12 Years from CIS high/very high risk, 3+ new T2, No CDMS Before 12m, 1st year treat % edss free % edss free high/very high risk, No Or 1-3 new T2, No CDMS Before 12m, 1st year treat High/very high risk score high/very high risk, No Or 1-3 new T2, No CDMS Before 12m, No 1st year treat High/very high risk score Time to edss 0 12 Years from CIS Time to edss 0 12 Years from CIS

7 Updated Risk calculator example

8 Calculating risks in MS

9 5. van der Zee, J. et al. A pan-european study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability, and pects of multiple sclerosis (MS) tential role f or salt as an MS rug performed well in clinical S drugs were shown to correlate MULTIPLE SCLEROSIS IN 2013 se progression. therapy for ALS and frontotemporal degeneration. Proc. Natl Acad. Sci. USA 110, E4530 E4539 (2013). Novel triggers, treatment targets and brain atrophy measures 2014); published online 7 January 2014; Can I improve my prognosis? that Xavier increased Montalban sodium and chloride Mar Tintoré concentrations can promote autoimmune diseases by stimulating 2013 witnessed induction advances of IL-17-producing many aspects of multiple sclerosis (MS) helper research. T (T H 17) Two cells studies from CD4 highlighted + T cells. Wu a potential role f or salt as an MS et trigger, al. showed and that one increased immunomodulator salt concentrations trials. in vitro Moreover, in mice treatment (via a high-salt effects diet) of MS drugs were shown to correlate y drug performed well in clinical induced inversely expression with brain of serum atrophy glucocorticoid and disease progression. kinase 1 (SGK1) in T cells and enhanced Montalban, X. & Tintoré, M. Nat. Rev. Neurol. 10, (2014); published online 7 January 2014; doi: / nrneurol Vitamin D Ross Everhard Dreamstime.com The year 2013 came to a close with improved understanding of how well-known environmental factors associated with multiple sclero sis (MS) contribute to the development of this disease. In addition, treatment advances have widened the scope to tackle brain atrophy and disease progression in patients with MS. The past 50 years have witnessed a marked increase in the incidence of autoimmune diseases, which has probably been driven by changes in environmental factors. Epidemiological Saltrisk factors for MS include vitamin D deficiency, exposure nrneurol com that increased sodium chloride concentrations can promote autoimmune diseases by stimulating induction of IL-17-producing helper T (T H 17) cells from CD4 + T cells. Wu et al. showed that increased salt concentrations in vitro or in mice (via a high-salt diet) induced expression of serum glucocorticoid kinase 1 (SGK1) in T cells and enhanced Smoking BMI Epstein Barr virus

10 Is there a treatment for me? DRUGS LICENCED TO TREAT RELAPSING MS Interferon beta 1a s.c. Interferon beta 1b s.c. Interferon beta 1a i.m. Glatiramer acetate Mitoxantrone Natalizumab Fingolimod Teriflunomide Fumarate Peg IFN Alemtuzumab Daclizumab Ocrelizumab

11 Which is the risk benefit ratio? Benefit Risk

12 Shared Decision is crucial when discussing treatment options Patient and Disease Profile Therapy Attributes Patient Preferences Geographic and Economic Factors

13 Many questions will araise during MS journey Relapsing-remitting Secondary progressive Primary progressive

14 Which are the risks of a pregnancy for my disease? Which problems multiple sclerosis can cause to my pregnancy?

15 Why I am so fatigued? Frequency: 75-95% Main symptom: 50% Interferes with quality of life No existing treatment Bakshi R et al Mult Scler 2003; Freal JE et al, 1984; Branas P et al., 2002

16 What about depression? Frequency, lifetime: 40-55% Frequency, 12 months prevalence: 25% Interferes with quality of life Should be identified and treated Fromont A, et al J Neurol 2013; Marrie RA, et al. BMC Neurol 2013;13:16.Marrie RA, Neurology 2016

17 Probability I have been fired out. Unemployment Probability of Remaining in Active Employment After Onset of MS 1.0 Control Persons MS Patients Time (years) Pfleger CC et al. Mult Scler. 2010;16:

18 Probability Divorce and Separation Crude Probability of Remaining in a Relationship After Onset of MS* Population Controls MS Patients Time to Event or End of Observation (years) *Life table method. Pfleger CC et al. Mult Scler. 2010; 16:

19 What about my earnings? 5 years after diagnosis Mean earnings of MS patients: 72% of earnings among References Higher education/qualified occupation Higher levels of earnings Largest relative differences Those with lowest level of earnings lower education less qualified occupations Exception: Managers Large difference MS vs Ref MS % of Ref All % Education -Higher % -Secondary % -Lower 84 53% Occupation Managers % Office % Manual % Unknown % No work 28 68% (1000 SEK ~100 Euro) ECTRIMS, Barcelona 2015 Michael Wiberg

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21 MRI