What do dermatologists and patients need from topical formulations?

Transcription

1 Dermatology and Topical Formulation 11:15-11:50 h What do dermatologists and patients need from topical formulations? Richard Weller University of Edinburgh, United Kingdom What do dermatologists and patients need from topical formulations? Richard Weller MD, FRCP University of Edinburgh Department of Dermatology & Centre for Inflammation Research

2 Active research areas affecting topical treatments Sunblocks The good and the bad. Novel treatments Microbiome Skin Barrier Eczema prevention 1. Intelligent sunblock not all sun is bad. Sunblocks (A and B) prevent Sunburn Photoaging Non melanoma skin cancer But what about: Vitamin D Contact sensitisation General health?

3 Serum vitamin D levels inversely correlate with BP and CVD Ann Intern Med. 2010;152(5): Serum vitamin D levels inversely correlate with Diabetes and metabolic syndrome Levels of vitamin D and cardiometabolic disorders: Systematic review and meta-analysis Johanna Parker, Omar Hashmi, David Dutton, Angelique Mavrodaris, Saverio Stranges, Ngianga-Bakwin Kandala, A... Maturitas, Volume 65, Issue 3, 2010,

4 Fig 2 Association of circulating 25-hydroxyvitamin D concentrations with all cause mortality, based on primary prevention cohorts. *Indirect comparisons based on available studies with relevant information in each category; summary estimates presented were calculated using random effects models. Chowdhury R et al. BMJ 2014;348:bmj.g by British Medical Journal Publishing Group Oral Vit D supplementation has no effect on BP Ann Intern Med. 2010;152(5):

5 .or IHD, Stroke or Cancer Bolland et al. Lancet Diabetes Endocrinol No Vitamin D causation Vitamin D Health Osteomalacia All cause Cardiovascular BP Stroke MS Metabolic synd DM IBD

6 but what about skin cancer? Entire Danish population aged > million individuals Confounders Occupation Education Exposures NMSC MM Outcomes MI Hip fracture Death but what about skin cancer? Non-melanoma skin cancer. OR all cause death ( ) OR MI 0.87 ( )

7 Melanoma in Southern Sweden Lindqvist et al. J Int Med ,000 Swedish Women 20 years follow up Sun habits Sun bed use Summer sunbathing Winter sunbathing Foreign hols Confounders Marital status Education Income Smoking Alcohol Pregnancies Comorbidity DM/Anticoag/CVS BMI Exercise Sun exposure Alive Dead HR 95%CI Ref Lindqvist et al. J Internal Med. 2014

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9 an ambitious and unique study: it was conducted in a region with the highest rate of skin cancer in the world, had a follow-up period of 10 years after the trial, and achieved relatively high rates of compliance among the participants assigned to the group using sunscreen. 4 Gimotty and Glanz JCO this carefully executed and ambitious study is commendable Hensin Tsao. NEJM Journal Watch 2011 unprecedented and is not likely to be replicated given the magnitude of the study, the long-term follow-up, and the high rate of compliance of participants. Bigby and Kim. Arch Derm Nambour Skin Cancer Prevention Trial follow-up profile. Green A C et al. JCO 2011;29: by American Society of Clinical Oncology

10 Nambour Skin Cancer Prevention Trial follow-up profile. Green A C et al. JCO 2011;29: by American Society of Clinical Oncology Nambour Skin Cancer Prevention Trial follow-up profile. Dead Alive Sunblock Control p= by American Society of Clinical Oncology Green A C et al. JCO 2011;29:

11 Nambour Skin Cancer Prevention Trial follow-up profile Green A C et al. JCO 2011;29: by American Society of Clinical Oncology

12 Can we make better sunblock?

13 2. The skin microbiome and disease The skin microbiome and disease

14 Regional skin disease Development of skin disease Modified hygiene hypothesis Persistent/recurrent infection Grice and Segre Nature Reviews Microbiology 9, (April 2011) doi: /nrmicro2537

15 Grice and Segre Nature Reviews Microbiology 9, (April 2011) doi: /nrmicro2537

16 Emollients and skin flora Current technology Cetrimide Fusidic acid Antibiotics Can we encourage a healthy flora? What is a healthy flora? How determined? Regional preparations?

17 3. Skin barrier and eczema AD- 20% of all children Atopic march Incidence has plateaued Risk of occupational dermatitis

18 Figure 1 Journal of Investigative Dermatology (2009) 0, doi: /jid Increased resting TEWL in subjects with FLG null mutations Mean resting TEWL g/m 2 /hr (a) FLG null n=19 P=0.009 WT n=60 Mean resting TEWL g/m 2 /hr (b) FLG null AD n=11 * WT AD n=42 FLG null non AD n=8 WT non AD n=18

19 Response to tape-strips is significantly higher in unaffected forearm skin of those with FLG-null mutations P=0.025 P=0.009 *** (a) (b) (c) * * * FLG null n=19 WT n=63 AD n=52 Non-AD n=25 FLG null AD n=12 WT AD n=45 FLG null non AD n=7 WT non AD n=18 Filaggrin deficiency correlates with activated APCs independently of eczema A B p=< P= % CD11c hi cells % CD11c hi cells 0 0 WT non-ad WT AD FLG-null non-ad FLG-null AD WT FLG-null

20 Can we prevent eczema with emollient therapy? Conclusions Are we doing things right? Broad based sunblock Non-specific antiseptic/antibiotic preparations How does new disease understanding affect our agents? What opportunities are available for new therapies? Collaborations? Devices/medicines/cosmeceuticals