SEVERE ASTHMA /BIOMARKERS Joint WORKING GROUP MEETING Co-chairs: Leif Bjermer & David Price Administration: Optimum Patient Care (OPC) DATE: Saturday 9th September 2017 TIME: 15.50 VENUE: Meliá Milano, Via Masaccio 19, Milan

Meeting attendees Arata Azuma Sajid Hansraj Alvaro Cruz Victoria Carter K F Chung Marcela Gavornikova Fulvio Braido Sheri Rogers Akio Niimi Dragos Bumbacea Ulla Seppala Akio Niimi Renaud Louis Kjell Alving Danny McBryan David Price Alberto Papi Richard Costello Glenn Crater Leif Bjermer Heather Hoch Therese Lapperre Mohsen Sadatsafavi Heather Hoch Pascal Pfis Lakmini Bulathsinhala

Agenda 15.50 -15.55 Welcome / Introduction Leif Bjermer & David Price 15.55 – 16.10: REG Projects 2017 Use of electronic medical records and biomarkers (published ECRJ 2017) David Price/Author present NICE/GINA FENO letter to the Editor: Kjell Alving OPC & OPRI Biomarker & Severe Asthma Projects David Price 16.10 –16.20 ISAR Initiative & Data Sources Update International Severe Asthma Registry (ISAR) Lakmini Bulathantisia Optimum Patient Care Research Database (OPCRD) Victoria Carter 16.20–16.40 New Projects & Initiatives New Projects Discussion All

REG SEVERE ASTHMA /BIOMARKERS Projects : ERS 2017 Update

Use of electronic medical records and biomarkers to manage risk and resource efficiencies Biomarkers used in isolation or combination are powerful composite metrics for predicting future risk. Promise of greater clinical insight through combining FeNO and blood eosinophil values to generate a ‘composite inflammatory biomarker An integrated EHR remains the ultimate goal, a ‘big data’ scenario - containing standard clinical information, new biomarker results, and behavioural/contextual data from connected devices M. Kerkhof1*, T. Tran2, M. van den Berge3, G. Brusselle4, G. Gopalan2, R. Jones5, J. Kocks3, A. Menzies-Gow6, J. Nuevo2, I. Pavord7, S. Rastogi2, D. Price1

Use of electronic medical records and biomarkers to manage risk and resource efficiencies

GINA / NICE FeNO Editorial Update Update from Kjell Alving – paper has been written but rejected from Lancet RM Update on the formal NICE publication Decision of next steps in regard to the paper Kjell to rework for re-submission of this paper to ERJ M. Kerkhof1*, T. Tran2, M. van den Berge3, G. Brusselle4, G. Gopalan2, R. Jones5, J. Kocks3, A. Menzies-Gow6, J. Nuevo2, I. Pavord7, S. Rastogi2, D. Price1

Predictive value of FeNO in patients with non-specific respiratory symptoms: a randomised controlled trial For every 10ppb increase in baseline FeNO, the improvement of ACQ was 0.071 greater in the extrafine ICS arm compared to the placebo arm

Health care resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population Less than 1% of patients in a UK general asthma population sample have SUEA

Rate Ratio of exacerbations Assessing the Use of FeNO and blood eosinophils as biomarkers in predicting asthma exacerbations Rate Ratio of exacerbations Lower CI (95%) Higher CI (95%) High FeNO and low BEC (n=98) 1.35 0.99 1.84 High BEC and low FeNO (n=186) 1.41 0.91 2.19 High BEC AND high FeNO (n=53) 1.72 1.00 20.93 The presence of FeNO ≥35ppb and BEC ≥300/µL adds to the accuracy in identifying patients who are at risk of exacerbation, compared to the presence of FeNO or BEC alone.

International Severe Asthma Registry Lakmini Bulathsinhala 9 September 2017

Live EDC System: CISIV Core variables: User Acceptability Testing (UAT) phase (complete Sept.11 2017)

Severe Asthma: Available Data Sources? First year of ISAR (2017): over 1000 patients records Expected start of data collection: Oct 2017 Data from the latest three years as of Dec 2017 OPCRD: a 3.4 million patient repository of routinely collected primary care data in UK. ISAR severe asthma patients’ primary care data linked to secondary care data benchmark analyses

ISAR SC : 2017 Research Prioritisation Research Topic Rank Feasibility Demographic, clinical characteristics, comorbidities, medical management of Severe Asthma patients worldwide 1 Yes Predictors of biologic response failure 2 Yes, Limited* Biologics progressing patient proportion 3 No Late versus early onset of Severe Asthma 4 Adherence (Quality use of therapy) 5 Quality of Life in Severe Asthma 6 Overlap in collected Biomarkers 7 Economic Burden of Severe Asthma 8 Asthma in young adults 9 Asthma in elderly 10 Characteristics of Asthma & COPD Overlap Syndrome in patients with severe asthma 11 Incidence of hidden severe asthma patients in primary care 12 * Variables not in core list or low sample size expected in 2017

Global Research Project: Timeline 2018 2017

ISAR Website and Publicity ISAR website: portal to raise awareness and passive recruitment Has been launched live in lieu of the ISC Meeting

Optimum Patient Care Research Database Victoria Carter 9 September 2017

OPCRD Biomarkers Data Category All Patients Number of records Asthma Patients COPD Patients Total 3,924,855 1,082,143,922 (Clinical) + 662,073,163(therapy) 798,546 152,788 Asthma Dx. (QoF) 3,527,324 46,750 COPD Dx. (QoF) 1,061,308 Rhinitis Dx 560,888 1,266,952 215,376 18,788 C reactive protein 655,264 1,929,812 152,335 47,550 Eosinophil Reading 2,131,253 13,060,575 474,294 126,916 FeNO 994(routine)+ 1156(clinical data) 1289(routine) + 1454(clinical data) 789(routine) + 1156(clinical data) 56 FeNO and Eosinophil reading 766 5,803 603 55 Neutrophil 1,586,976 8,538,834 322,151 86,197 Vitamin D level 54,291 139,283 12,805 3,526

New Project Ideas / Group Discussion

Previous Study Ideas from the Working Group… Evaluate the utility of blood eosinophils as a predictor of outcomes Utility of blood eosinophils as a predictor of response to therapy – dual bronchodilation vs ICS/LABA Link between smoking and FENO level Consider pulmonary vs systemic drivers of high blood eosinophils Link between eosinophenia and increase risk of pneumonia Consider opportunities to use biomarkers in the upper airway Incidence of hidden severe asthma patients in primary care M. Kerkhof1*, T. Tran2, M. van den Berge3, G. Brusselle4, G. Gopalan2, R. Jones5, J. Kocks3, A. Menzies-Gow6, J. Nuevo2, I. Pavord7, S. Rastogi2, D. Price1