trevor pickersgill, looking to the future, treatments
TRANSCRIPT
Looking to the Future: Next 21yrs
Dr Trevor Pickersgill
Consultant Neurologist
University Hospital of Wales
Royal Glamorgan Hospital
Declarations• Research post 1996-8 - Schering AG ESPMS trial• Travel/Conference hospitality: Biogen-Idec, Merck-Serono, Novartis, Roche,
Sanofi-Genzyme• Advisory Board Remuneration/Honoraria: Biogen-Idec, Teva, Roche,
MedDay, Novartis, Merck-Serono• Educational Grants: GSK, Teva, UCB • Director & Trustee: Association of British Neurologists; Hospital Medical
Staffs Defence Trust• Council Member: ABN, BMA
What do we want?
• Technology....?• Crystal ball• Drugs drugs drugs
• Anti-inflammatory• Restorative/remyelinative• protective
• ‘cure’.....
RM dob 1987….inflammation in 2005(18)
….atrophy 2012….
• Fig 2. Comparison of the survival in MS patients with the survival of the French general population.
Leray E, Vukusic S, Debouverie M, Clanet M, Brochet B, et al. (2015) Excess Mortality in Patients with Multiple Sclerosis Starts at 20 Years from Clinical Onset: Data from a Large-Scale French Observational Study. PLOS ONE 10(7): e0132033. https://doi.org/10.1371/journal.pone.0132033http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132033
Kaplan-Meier survival curves of patients with multiple sclerosis (MS) in Hordaland county from birth (left column: A, C, E, G) and from disease onset (right column: B, D, F, H).
Hanne-Marie Bøe Lunde et al. J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2016-315238©2017 by BMJ Publishing Group Ltd
What can we do to stop PWMS dying and getting disabled?
More better drugs...?
• “me-too” xxxxxxxxx-mabs• New kids in a crowded market
• Need to be game changing (easy....oral....)• Or cheap.....• Or risk-free......
• Identifying new immune targets• Leads to more and unexpected problems..?
Treatment with disease‐modifying drugs for people with a first clinical attack suggestive of multiple sclerosis
Cochrane Database of Systematic Reviews25 APR 2017 DOI: 10.1002/14651858.CD012200.pub2http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD012200.pub2/full#CD012200-fig-0007
Organised inpatient (stroke unit) care for stroke
Cochrane Database of Systematic Reviews11 SEP 2013 DOI: 10.1002/14651858.CD000197.pub3http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000197.pub3/full#CD000197-fig-00109
Odds of death occurring by end of scheduled follow up in stroke unit compared with conventional care.
British Medical Journal Publishing Group BMJ 1997;314:1151©1997 by British Medical Journal Publishing Group
Odds ratio (95% confidence interval) of death or requiring institutional care at the end of scheduled follow up in patients receiving stroke unit compared with conventional care.
British Medical Journal Publishing Group BMJ 1997;314:1151©1997 by British Medical Journal Publishing Group
• HASU......
• HANU.....HABU...?
• Regional Units 8 beds...?
• Does it really add up?
What about prevention?
Cox proportional hazard regression graph showing survival from birth (A) by lifelong smoking status and (B) latest smoking status.
Improving Disability?
Estimates of differences between treatments:
Highly significant difference between treatments, but not periods.
TreatmentEffect
Estimateddifference
95% CI
Hospital - None 1.4 0.62, 2.14
Home - None 1.5 0.73, 2.26
Home - Hospital 0.1 -0.65, 0.87
Neuroprotection: Atrophy
What about the biology...
• More PMs• More pathology research/brain bank• More risk factors• Smoking• Vit D• Infection• Genes
• Biomarkers....Bioprediction• Neurofilament NFL - CSF (serum)• Genetic array
And more trials in Progressive MS!!