Final report V1.5 16 th January 2020 1 Observational and Pragmatic Research Institute Pte Ltd Final report Hidden Severe Asthma in Primary Care versus ISAR Cohort Describe the extent of hidden (not referred) patients with severe asthma in a primary care setting versus ISAR and compare their demographic and clinical characteristics Date: 16th January 2020 AZ contact: Marianna Alacqua & Trung N. Tran OPRI Pte Ltd 5 Coles Lane Phone +44 (0) 1223 967884 Blk 883 North Bridge Road, Oakington #02-05 Southbank Cambridge CB24 3BA Web site http://www.opri.sg Singapore 198783 United Kingdom 1 Final report V1.5 16 th January 2020 2 Chief Investigator: Professor David Price, Professor of Primary Care Respiratory Medicine and Director of Observational and Pragmatic Research Institute Pte Ltd Office number: +44 2081233923 Skype ID: respiratoryresearch Email: [email protected] Research Lead: Dr Heath Heatley Observational and Pragmatic Research Institute Pte Ltd 5 Coles Lane, Oakington, Cambridgeshire CB24 3BA, United Kingdom Email: [email protected] Study sponsor: AstraZeneca Primary contacts Marianna Alacqua & Trung N. Tran Email: [email protected] & [email protected] 2 Final report V1.5 16 th January 2020 3 Title Hidden Severe Asthma in Primary Care vs. ISAR Cohort Subtitle Describe the extent of hidden (not referred) patients with severe asthma in a primary care setting versus ISAR and compare their demographic and clinical characteristics Final report version 1.5 EU PAS Registration Number EUPAS28611 ADEPT Approval Number ADEPT0319 Country of study United Kingdom Author OPRI Pte Ltd Blk 883 North Bridge Road #02-05 Southbank Singapore 198783 3 Final report V1.5 16 th January 2020 4 Contents 1.0 BACKGROUND ................................................................................................................................................ 7 2.0 STUDY AIMS AND OBJECTIVES ..................................................................................................................... 10 2.1 AIMS ......................................................................................................................................................................... 10 2.2 OBJECTIVES ................................................................................................................................................................ 10 3.0 STUDY DESIGN ............................................................................................................................................. 11 4.0 STUDY POPULATIONS AND DATA SOURCES ................................................................................................. 13 4.1 OPTIMUM PATIENT CARE RESEARCH DATABASE ................................................................................................................ 13 4.2 INTERNATIONAL SEVERE ASTHMA REGISTRY ...................................................................................................................... 14 5.0 STUDY OUTCOMES ....................................................................................................................................... 15 5.1 STUDY GROUPS ........................................................................................................................................................... 15 5.1 STUDY OUTCOMES ....................................................................................................................................................... 15 5.2 STATISTICAL ANALYSIS ................................................................................................................................................... 20 6.0 RESULTS ....................................................................................................................................................... 21 6.1 ELIGIBLE PATIENTS ....................................................................................................................................................... 21 6.2 CATEGORISATION BY GINA (2018) TREATMENT , EXACERBATIONS AND BY REFERRAL ................................................................ 21 6.3 CATEGORISATION ACCORDING TO MAINTENANCE AND ACUTE OCS USE .................................................................................. 24 6.4 DEMOGRAPHICS BY PATIENT GROUPS ............................................................................................................................... 25 6.5 CLINICAL CHARACTERISTICS BY PATIENT GROUPS ................................................................................................................. 30 6.6 COMORBIDITY CHARACTERISTICS BY PATIENT GROUPS ......................................................................................................... 42 6.7 ADDITIONAL FOLLOW -UP ANALYSIS ................................................................................................................................. 44 7.0 SUMMARY ................................................................................................................................................... 47 8.0 APPENDIX .................................................................................................................................................... 49 8.1 ALGORITHM TO SEPARATE ACUTE AND MAINTENANCE OCS USE ............................................................................................ 49 8.2 CODE LISTS ................................................................................................................................................................. 50 9.0 RESEARCH TEAM ........................................................................................................................................ 120 10.0 REFERENCES ............................................................................................................................................... 121 4 Final report V1.5 16 th January 2020 5 Index of Figures Figure 1 - Study Design ................................................................................................................ 12 Figure 2 - Number of patients by GINA (2018) treatment step....................................................... 22 Figure 3 - Proportion of patients in primary care with (a) high maintenance therapy asthma and potential severe asthma and (b) proportion of those with potential severe asthma who were not managed in specialist care, i.e. “hidden patients”. ............................................................ 23 Figure 4 - Categorisation of patients as either probable maintenance or acute OCS users ........... 24 Figure 5 - Patient Group: Age ....................................................................................................... 26 Figure 6 - Patient Group: Gender .................................................................................................. 26 Figure 7 - Patient Group: Ethnicity ................................................................................................ 27 Figure 8 - Patient Group: Height ................................................................................................... 27 Figure 9 - Patient Group: BMI ....................................................................................................... 28 Figure 10 - Patient Group: Smoking Status ................................................................................... 28 Figure 11 - Patient Group: Exacerbations ..................................................................................... 34 Figure 12 – Patient Group: Exacerbation Count Per Year ............................................................. 34 Figure 13 – Patient Group: Asthma Control .................................................................................. 34 Figure 14 – Patient Group: Blood Eosinophil Count ...................................................................... 34 Figure 15 – Patient Group: BEC Histogram................................................................................... 35 Figure 16 - Patient Group: FEV 1.................................................................................................... 36 Figure 17 – Patient Group: % Predicted FEV 1 ............................................................................... 36 Figure 18 – Patient Group: FVC .................................................................................................... 36 Figure 19 – Patient Group: % Predicted FVC ................................................................................ 36 Figure 20 – Patient Group: FEV 1/FVC ratio ................................................................................... 37 Figure 21 – Patient Group: Peak Expiratory Flow.......................................................................... 37 Figure 22 – Patient Group: Adherence .......................................................................................... 37 Figure 23 – Patient Group: ICS combination medication ............................................................... 37 Figure 24 – Patient Group: SABA, Theophylline and Biologic Medication ..................................... 38 Figure 25 – Patient Group: Comorbidities ..................................................................................... 43 Figure 26 – The number of patients with potentially severe asthma with referral records at any time .............................................................................................................................................