Changing the paradigm for liver disease - Nick Sheron
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The eighth presentation delivered at the 'Big Data in health and care: using data to gain new insights’ event, hosted by Wessex Academic Health Science Network (AHSN) on 19 April 2015.
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Digital Editing Software: Photoshop is commonly used by designers to edit
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Spanish University for Distance Education, UNED
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This document discusses hypertension (high blood pressure). It defines hypertension and provides normal and elevated blood pressure readings. It describes the types and causes of primary and secondary hypertension. It discusses the risk factors, mechanisms, diagnosis, clinical presentation, complications and treatment of hypertension, including lifestyle modifications and medication options. The goal of treatment is to reduce blood pressure levels to lower the risks of complications like stroke, heart disease and kidney damage.
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Cell Therapy Expansion and Challenges in Autoimmune Disease
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
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Changing the paradigm for liver disease - Nick Sheron
- 1. 0 20 40 60 80 100 120 % Years Percentage change in standardised UK mortality rates (age 0-64) normalised to 100% in 1970 circulatory ischaemic heart cerebrovascular neoplasms respiratory endocrine / metabolic diabetes Data from WHO-HFA database downloaded Oct 2013
- 2. 0 100 200 300 400 500 600 % Years Percentage change in standardised UK mortality rates (age 0-64) normalised to 100% in 1970 circulatory ischaemic heart cerebrovascular neoplasms respiratory liver endocrine / metabolic diabetes Data from WHO-HFA database downloaded Oct 2013
- 3. Sheron, Gilmore BMJ 2015 in press Liver mortality Directly attributable alcohol mortality
- 4. Williams et al Lancet 2015 0100200300400500 1980 1983 1986 1989 1992 1995 1998 2001 2004 2007 2010 %changesince1980 Trends in mortality from alcohol related liver disease in England and Wales , consumption of spirits, wine, beer and cider, and changes in duty Alcohol related liver deaths E&W % White spirits consumption % Whisky consumption % Cider consumption % Wine consumption % Total lager / beer consumption alcohol % Packaged strong lager %
- 6. Dr Foster data, in-hospital mortality all E &W acute trusts
- 7. Nick Sheron, unpublished analysis Survival of admissions to the Liver Unit Southampton 1/3 1/3 1/3
- 8. 76% P<0.001 Prior liver outpatient referrals in 5,112 Southampton first admissions with cirrhosis Nick Sheron unpublished analysis ¾ of people who will die of cirrhosis have no idea they are ill
- 12. Liver cell Liver Enzymes eg ALT, AST, ALP, GGT
- 13. Necrosis = cell swells, membrane leaks, enzymes escape Liver enzymes are raised in blood Viral hepatitis Autoimmune hepatitis
- 14. necrosis apoptosis Cell shrinks with membrane intact
- 15. necrosis apoptosis Liver enzymes normal Alcohol Obesity
- 17. The current system for treating liver disease doesn’t work Because it picks up people too late
- 18. The Southampton Liver Traffic Light Test 4,343 subjects followed for 12 years
- 19. 30% reduced drinking to safe levels 65% reduced drinking to safe levels Traffic light test given to 400 heavy drinkers in primary care follow up data at one year
- 21. Emma Greatorex, Katie Minards, David Cable, Alan Hales Biochemistry data Haematology data Endoscopy data PAS data Pathology data Hampshire Health Record data
- 22. Acknowledgments: POLeMMIC Colin Newell Magdy El-Gohari Emily Stimpson Jo Dash Tina Reinson Jackie Hollis Lucy Gruner Maria Baggot Natalie Stanton Wendy O’Brien Andrea Jarman Mike Moore Paul Roderick Julia Sinclair Miranda Kim Maheswaran Naranjan Topher Woelk Data: HHRIGG NHS SCW CSU Funding: British Liver Trust NIHR BRC