Individuals with filaggrin-related eczema and asthma have increased long-term medication and hospital admission costs P. Soares, 1 K. Fidler, 1 J. Felton, 1 R. Tavendale, 2 A. Hövels, 3 S.A. Bremner, 1 C.N.A. Palmer, 2 S. Mukhopadhyay, 1 1 Brighton & Sussex Medical School, Brighton, UK. 2 University of Dundee, Dundee, U.K. 3 Utrecht University, Utrecht, The Netherlands British Journal of Dermatology. DOI: 10.111/bjd.16720

The lead researcher of the study Professor Somnath Mukhopadhyay Chair of Paediatrics Royal Alexandra Children’s Hospital Brighton and Sussex Medical School United Kingdom

Introduction What’s already known? Filaggrin gene defects are associated with the development of eczema in children. Filaggrin gene defects are associated with severe and persistent eczema and severe asthma.

Objective The aim of this study was to determine whether filaggrin mutations are associated with increased prescribing of medication for eczema and asthma and /or an increased number of asthma exacerbations in children and young adults and whether this translates into different healthcare costs.

Methods (1) BREATHE is a cross-sectional study of gene-environment interactions in 1100 children and young adults with physician- diagnosed asthma aged between 2 and 22 years. All participants in BREATHE were linked with the Scottish Morbidity Records-01 database, the Accident and Emergency database of Tayside, Scotland and the Community Pharmacy database.

Methods (2) All participants were followed for 9 years, from 2005 to 2013. Variables included in the analysis were filaggrin status, family history of eczema and asthma, cat ownership, age, gender, self-report of eczema and four filaggrin polymorphisms, common in the Caucasian population. The four polymorphisms were combined into two categories: no FLG mutation vs. one or more FLG mutations.

Methods (3) The outcomes are the number of eczema and asthma-related prescriptions dispensed and asthma exacerbations per patient for each year. The analyses regarding eczema were performed on 530 children and adults with eczema and asthma; the analyses concerning asthma were performed on 978 children and adults.

Methods (4) A cost analysis was performed on the prescribed medication based on Scottish (Information Service Division) prices obtained from 2005 to 2013.

Results (1) A strong association was found between the presence of filaggrin mutations and the number of emollients dispensed (IRR: 2.19, 95% CI: 1.36-3.52), and the presence of filaggrin mutations and the number of prescriptions dispensed for severe eczema (IRR: 2.18, 95% CI: 1.22-3.91).

Results (2) A strong association was found between the presence of filaggrin mutations and the number of LABA with ICS dispensed (IRR: 3.29, 95% CI: 1.68-6.43). Overall, children and adults with filaggrin mutations had significantly more asthma exacerbations than children and adults without filaggrin mutations (IRR: 1.76, 95% CI: 1.27-2.45).

Results (3) There was a £1182 (BCa CI: £258-£3012) difference in costs between children and adults with eczema and asthma with and without filaggrin mutations over a nine-year period of study. The figure is similar considering individuals with asthma, regardless of having eczema. Children and adults with filaggrin mutations and asthma cost £1076 (BCa CI: £335-£2366) more than children and adults without filaggrin mutations.

Discussion (1) Considering the prescribing cost for eczema, asthma and hospitalisations, one can extrapolate that over a nine-year period the NHS in Scotland may spend approximately an additional £1,918,000 (estimates vary between £598,000 and £4,218,000) treating children with asthma and filaggrin mutations than children with asthma without filaggrin mutations.

Discussion (2) Interventions can be targeted towards a population with disease carrying a specific biological and genetic defect. Targeted genotyping and precision medicine-based interventions from early childhood could in the longer term offer many decades of lower prescribing and reduced hospital costs.

Discussion (3) A major benefit of precision medicine in common chronic disease could be the more rational use of currently available therapies, such as daily use of emollients since birth, leading to major cost savings for healthcare systems and improvements in disease control and quality-of-life.

Discussion (4) What are the implications of having a gene test available at birth that predicts a person’s long-term cost to society? How large are differences between individuals when genetic profiling for thousands of genes become widely available? How large are these differences when compared over entire lifetimes?

Discussion (5) Do these differences pose additional questions for privatised healthcare systems where financial risk assessment is critical? As with the NHS moving towards privatisation, these issues could come closer to home.

Conclusions What does this study add? Patients with filaggrin gene mutations were dispensed more prescriptions for both eczema and asthma and had more asthma exacerbations over a nine-year period of study. This translates to higher costs for these patients. However children and adults with filaggrin gene mutations may benefit from targeted treatment regimes which could reduce morbidity and longer-term treatment costs.

Prof. Somnath Mukhopadhyay The research team Dr Roger Tavendale Prof. Colin Palmer Dr Jessie Felton Patricia Soares Prof. Somnath Mukhopadhyay Dr Stephen Bremner Dr Katy Fidler Dr Anke Hövels

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