trevor pickersgill, looking to the future, treatments

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!!