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Research Update

Research Update. Marwa Kaisey, MD National MS Society Regional MS Summit September 28 th , 2019. Disclosures. Speaking & Consulting for Biogen, Genentech, and Celgene. Overview. Diagnostic criteria – what’s new, misdiagnosis Central vein/new imaging Neurofilament New DMTs

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Research Update

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  1. Research Update Marwa Kaisey, MD National MS Society Regional MS Summit September 28th, 2019

  2. Disclosures • Speaking & Consulting for Biogen, Genentech, and Celgene Neurology

  3. Overview • Diagnostic criteria – what’s new, misdiagnosis • Central vein/new imaging • Neurofilament • New DMTs • Remyelinating treatments • Stem cell treatment

  4. How do we diagnose MS? Neurology

  5. History of Multiple Sclerosis Diagnostic Criteria Charcot (1868) “La sclerose en plaques disseminees” Marburg (1906) anothertriad Allison and Millar (1954) “an arbitrary scheme” Broman (1965) dissemination in space and time McDonald (2005) Clinical evaluationstill important! Schumacher (1965) clinically definite McDonald (2017) CSF makes a come-back McDonald (2010) Diagnose with a single MRI McDonald (2001) MRI wide-spread McAlpine (1972) similar to Allison and Millar Rose (1976) similar to Schumacher McDonald and Halliday (1970s) evoked potentials Poser (1983) laboratory-supported definite and probable Neurology

  6. 2017 McDonald Criteria • STILL have to prove dissemination in space and dissemination in time of typical • symptoms with no alternate diagnosis. • Clinical • MRI • CSF (can now be used to replace dissemination in time)

  7. 2017 McDonald Criteria Neurology

  8. 2017 McDonald Criteria Neurology

  9. 2017 McDonald Criteria – The Updates Dissemination in time - new lesion on follow-up MRI OR - simultaneous enhancing* and non-enhancing lesions OR - CSF oligoclonal bands* *new in 2017 • Dissemination in space • - T2 hyperintense lesions in 2+ areas: • Periventricular • Juxtacorticalor cortical* • Infratentorial • Spinal cord Neurology

  10. So are we now perfect at diagnosing MS? Neurology

  11. Misdiagnosis: a big problem in multiple sclerosis “These brain cuttings were popular sessions… On one memorable occasion, we examined the brains of five patients who had been diagnosed in life as having multiple sclerosis. The brain cuttings, however, revealed that all of them had been misdiagnosed.” – Oliver Sacks, On the Move, 2015. Neurology

  12. Misdiagnosis in multiple sclerosis Neurology

  13. Misdiagnosis in multiple sclerosis Neurology

  14. Underdiagnosis Misdiagnosis in multiple sclerosis Overdiagnosis

  15. Misdiagnosis in multiple sclerosis

  16. New patients referred to Cedars-Sinai and UCLA neuroimmunology clinics July 2016-June 2017 Kaisey et al, unpublished

  17. New patients referred with firm diagnosis of MS July 2016-June 2017 17% do not have MS 19% do not have MS

  18. Final diagnosis in misdiagnosed patients Kaisey et al Neurology

  19. Final diagnosis in misdiagnosed patients Neurology

  20. Characteristics of patients with MS misdiagnosis Cedars-Sinai (n=115) UCLA (n=127) Multiple logistic regression α = 0.05

  21. How do we more accurately diagnose MS?

  22. New MRI techniques Neurology

  23. New MRI techniques: Central vein Absinta, 2016

  24. New MRI techniques: Central vein neuropathology-web.org

  25. New MRI techniques: Central vein

  26. New MRI techniques: Central vein

  27. New MRI techniques: Central vein

  28. New MRI techniques: Central vein

  29. What about new tools to monitor the disease over time?

  30. New serum tools: neurofilament light chains

  31. New serum tools: neurofilament light chains Gaetani et al. J Neurology, Neurosurgery & Psychiatry 2019

  32. New serum tools: neurofilament light chains Disanto et al, Annals of Neurology, 2017

  33. New serum tools: neurofilament light chains Nfl increases with: -age -other neuordegerative disease -brain injury Disanto et al, Annals of Neurology, 2017

  34. New serum tools: neurofilament light chains How do we more accurately diagnose MS? Barro et al. Brain 2018

  35. New serum tools: neurofilament light chains

  36. New serum tools: neurofilament light chains

  37. How do we know which treatment to pick for which patient?

  38. RRMS Treatment Selection

  39. What new treatments are on the horizon?

  40. MS Phenotypes Lublin et al, Neurology 2014

  41. MS Phenotypes Courtesy of National MS Society

  42. New(ish) MS Treatments • Cladribine – oral – purine analog (/azathioprine)

  43. New(ish) MS Treatments • Cladribine – oral – purine analog (/azathioprine) • Siponimod – oral – S1P1 (P5) receptor mod (/fingolimod)

  44. New(ish) MS Treatments

  45. New MS Treatments • Novel mechanism: evobrutinib – • Burton’s Tyrosine Kinase (BTK) inhibition

  46. New MS Treatments • Novel mechanism: evobrutinib – • Burton’s Tyrosine Kinase (BTK) inhibition • Phase III: evbobrutini BID PO vs interferon beta-1a IM

  47. New MS Treatments • Novel mechanism: evobrutinib – • Burton’s Tyrosine Kinase (BTK) inhibition • Phase III: ebobrutini BID PO vs interferon beta-1a IM • Target completion in 2023

  48. So we’re getting even better at preventing new activity. How about repairing old damage?

  49. Remyelination Strategies • Opicinumab (anti-Lingo 1)

  50. Remyelination Strategies • Opicinumab (anti-Lingo 1) • RENEW, Cadavid et al, Lancet Neurology 2017 • Phase II in acute ON • VEP • vs. placebo

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