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Switching DMDs and new pipeline therapies - Dr Eli Silber
The document discusses the current landscape of multiple sclerosis (MS) therapies, focusing on the need for new treatments, switching strategies, and classification challenges of progressive MS. It highlights the complexity of treatment decisions, risks associated with various therapies, and the importance of patient-specific factors in determining treatment efficacy and safety. Additionally, the document outlines recent trends in disease-modifying therapies and the outcomes of stem cell transplants at King's College Hospital.
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Switching DMDs and new pipeline therapies - Dr Eli Silber
- 1. Switching DMDs andnew pipeline therapies Dr Eli Silber Consultant neurologist Kings College Hospital
- 2. Outline • Where arewe now – Therapies • Uncertainties – Induction v.s escalation v.s. rescue – Modelling outcomes – What is progressive disease, SP &PP – Risk reduction • Why is there a need for new therapies? • When is there a need to switch? Silber; MSRT 2016
- 3. A double edgedsword Safety First line B Interferon Copaxone Nil Natalizumab JCV Pos Alemtuzumab Fingolimod DMF Natalizumab JCV -ve Teriflunomide 0% 30% 50% 70% Silber; MSRT 2016 Efficacy: Reduction in relapse rate
- 4. Choice of therapy Disease Severity;Relapses MRI Disability Patient Attitude to risk Work/ lifestyle Pregnancy Funding/ Guidance Silber; MSRT 2016
- 5. Induction v.s. escalationv.s. rescue Silber; MSRT 2016
- 6. How we decidewho is going to do badly? At onset • Gender/ age / race • Relapses – Number – Site – Recovery? • MRI – Lesion load/ T1 During therapy • Rio scores – Clinical – MRI Silber; MSRT 2016
- 7. Early attacks predictlong term disability Silber; MSRT 2016
- 8. Rio & modifiedRio scores help to predict long term prognosis after DMTs have been started Imperial study day September 2016
- 9. How useful andachievable is NEDA? Silber; MSRT 2016
- 10. How you youdefine treatment failure? Silber; MSRT 2016
- 11. What do wemean by progressive disease? Silber; MSRT 2016
- 12. 1996 Classification ofMS Silber; MSRT 2016
- 13. 2013 Classification: Relapsingdisease Silber; MSRT 2016
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- 15. Progressive MS isdirty and complicated • Some SP patients relapse when DMTs are withdrawn • A minority of PP patients have a high lesion load and may respond to DMTs • Progression is like middle age….obvious after some time but the transition is variable • Many of my patients in a “grey area” Silber; MSRT 2016
- 16. What to dowith high JCV antibody positive natalizumab patients? Close monitoring “step down” or “step aside” • What drugs? • Fingolimod • What about DMF? • ? New agents such as dacluzimab Silber; MSRT 2016
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- 21. Adding to thespectrum Safety First line B Interferon Copaxone Nil Natalizumab JCV Pos Alemtuzumab HSCT Fingolimod DMF Natalizumab JCV -ve Teriflunomide 0% 30% 50% 70% Ocreluzimab Daclizumab Cladribine Silber; MSRT 2016
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- 24. Ocrelizumab in RRMS Silber; MSRT 2016
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- 27. Ocrelizumab in PPMS Silber; MSRT 2016
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- 31. Dacluzimab: Mechanism ofaction Silber; MSRT 2016
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- 40. ? Copy cator improved • Ponesimod – Selective SIP1 inhibitor – Shorter half life thus more rapid immune reconstitution – More selective- Fewer cardiac effects • Ofatunimab – Fully human monoclonal v.s. CD20 – Licensed in CLL Silber; MSRT 2016
- 41. Opicunimab: Anti-LINGO Silber; MSRT2016 EDSS T25F Walk 9RPT PASAT
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- 43. Going back tothe drawing board: Cladribine Silber; MSRT 2016 Oracle MS: Cladribine reduces the risks of converting to CDMS
- 44. Cladribine vs. placeboin RR MS Silber; MSRT 2016
- 45. HSCT: Magic bulletor snake oil • Three types of stem cells – Regeneration- experimental (Mesenchymal) – Reconstitution post immune ablation (HSCT) – The charlatans Silber; MSRT 2016
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- 50. HSCT at King’sCollege Hospital • 30 transplants completed at KCH (with further 8 awaiting) • Detailed audit ongoing of transplant process with short/long term outcomes Year Number of transplants 2012 4 2013 3 2014 3 2015 9 2016 11 Gender N (%) Female 16 (53.3) Male 14 (46.7) MS type N (%) RRMS 18 (60) SPMS 10 (33.3) PPMS 2 (6.7) Average age at transplant (range) Overall 41.2 (22-60) Female 38.3 (29-60) Male 43.8 (22-49)
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- 52. Thank you: LEJOG2016 Silber; MSRT 2016
Editor's Notes
- #51 The further 8 will be transplanted late 2016/early 2017 No mortalities Following up a further 2 patients transplanted in 2009 and 2011 at GSTT (both male with SPMS) Audit looking at aspects such as time since first symptom/diagnosis, disability scores/MRI results before and after transplant, number of DMT’s tried before transplant etc.