Prescription patterns of asthma preventers among paediatric patients in South Korea : ICS or montelukast?

다국어 초록 (Multilingual Abstract)

Background: Prescribing patterns of asthma preventers are diverse in different countries where ICS and montelukast are commonly used in young asthmatic patients. Our study was conducted to observe how South Korea prescribed asthma preventers among paediatric patients compared with other countries. With a recent announcement stated by the FDA regarding strengthening of ‘boxed warning’ on montelukast, our study focused on ICS and montelukast specifically among preventers.
Methods: The Health Insurance Review and Assessment Paediatric Patients Sample (HIRA-PPS) dataset 2018 was used in the study. Paediatric outpatients aged between 3 and 19 with asthma diagnostics (ICD-10, J45 and J46) with a history of a preventer and a reliever between Jan 1, 2018 to December 31, 2018 were selected. Preventers were defined as ICS, ICS+LABA, LTRA and sustained release xanthines. Study participants were divided into two age groups: 3-9 years as younger children group and 10-19 years as older children group. The proportion of patients on each preventer was calculated. To observe association between monteluakast compared with ICS and variables of interest, Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were estimated.
Results: LTRA was most widely prescribed with 90.6% in younger children group and 71.2% in older children group. Only 2.1% of younger patients were on ICS-based inhalers and 14.8% in older children. Proportion of patients on montelukast accounted for 73.4% as opposed to 4.8% on ICS-based inhalers. Compared with ICS, montelukast was more prevalently prescribed in younger age groups and in hospitals and clinics.
Conclusion: South Korea showed a strong preference towards LTRAs, especially montelukast over ICS. Considering an increase in neuropsychiatric side effects among paediatric patients after montelukast use, montelukast should be cautiously prescribed in asthmatic children.

국문 초록 (Abstract)

배경: 전세계적으로 소아 천식 유병률이 증가함에 따라 천식 예방약 처방 양상이 다양해지고 있다. 따라서, 다른 국가와 비교하여 한국 천식 약 처방약상을 연구하고자 한다. 최근 FDA에서 montelukast 관한 ‘boxed warning’ 강화발표를 참고하여 ICS와 montelukast를 구체적으로 비교하고자 한다.
자료 및 방법: 이 연구는 한국 건강보험심사평가원에서 제공하는 소아청소년환자 데이터셋을 활용하여, 소아환자군의 천식예방약 처방 양상 연구를 수행하였다. 연구대상은 2018년 1월 1일에서 2018년 12월 31일 사이 만 3세에서 19세 사이 소아청소년 외래환자 중 같은 ICD-10 천식코드 J45 또는 J46 내역과 천식 예방약과 및 천식 증상 완화약을 처방받은 내역이 있는 환자를 포함하였다. 천식예방약은 ICS, ICS+LABA, LTRA, xanthines로 정의하였다. 각 천식예방약 계열 별 속한 환자 수와 proportion을 산출하였다. Montelukast 처방양상이 ICS-based 흡입기 대비해 나이군, 성별, 의료기관 종류 그리고 시도 별 상대위험도 (Odds Ratio, OR) 및 95% 신뢰구간 (Confidence Intervals, CIs)를 산출하였다.
결과: LTRA를 복용하는 환자가 제일 많았다. 3-9살 소아환자 군에서는 90.6%, 10-19살 환자 군에서는 71.2%를 보였다. 반면 ICS-based inhalers를 복용하는 3-9살 환자는 2.1%였고 10-19살 환자군에서는 14.8%였다. 그 중 montelukast를 복용하는 환자는 전체 73.4%였고 ICS-based inhalers를 사용하는 환자는 4.8% 였다. ICS와 비교하여 montelukast 어린 환자 군 그리고 개인 병원 및 의원에서 처방이 많이 되는 양상을 보였다.
결론: 한국에서는 LTRA, 특히 montelukast를 복용하는 소아청소년 환자가 많았다. 소아환자군에서 montelukast 복용 후 신경정신 부작용을 생긴 점을 고려했을 때, 한국은 montelukast 처방이 많다. 따라서, 이 연구를 기반으로 하여 montelukast 관련 신경정신 부작용 연구진행 및 처방 시 주의가 필요로 하다.

목차 (Table of Contents)

• Chapter 1. Introduction 1
• 1.1 Background 1
• 1.2 Objectives 7
• Chapter 2. Literature Review 8
• 2.1 Previous studies on prescription patterns of asthma preventers in paediatric patients; western countries 8
• 2.2 Previous studies on prescription patterns of asthma preventers in paediatric patients; eastern countries 15
• 2.3 Previous studies on prescription patterns of asthma preventers in padiatric patients; South Korea 20
• Chapter 3. Material and Methods 25
• 3.1 Data source 25
• 3.2 Study design 30
• 3.3 Study subjects 32
• 3.4 Preventers definition 38
• 3.5 Relievers definition 40
• 3.6 Statistical analysis 41
• 3.7 Ethical approval 43
• Chapter 4. Results 44
• 4.1 Study population characteristics 44
• 4.2 Prescription patterns of asthma preventers by active ingredient 49
• 4.3 Prescription patterns of ICS and LTRA 52
• 4.4 Prescription patterns of ICS and montelukast in different types of medical institution 54
• 4.5 Association between montelukast and variables of interest 56
• 4.6 Association between ICS and variables of interest 58
• 4.7 Association between montelukast compared with ICS and variables of interest 61
• Chapter 5. Discussion 64
• 5.1 Comparison with previous studies; western countries 64
• 5.2 Comparison with previous studies; eastern countries 69
• 5.3 Comparison with previous studies; South Korea 74
• 5.4 Possible reasons behind asthma prescription pattern differences 77
• 5.5 Strengths 84
• 5.6 Limitations 86
• 5.7 Implications 89
• Chapter 6. Conclusion 93
• Reference 95
• Appendix 105
• Korean Abstract 121