探討台灣膀胱過動症的藥物流行病學

Evaluating the Pharmacoepidemiology of Patients with Overactive Bladder in Taiwan

周育如(Yu-Ju Chou)

指導教授 ： 陳崇鈺

高雄醫學大學/藥學院/藥學系臨床藥學碩士班/碩士(2020年)

摘要

研究背景與目的:
膀胱過動症是一個複合性症候群，包含尿急、夜尿、頻尿及尿急性尿失禁。雖然這是一種非致命性的疾病，但其幾乎無法被治癒，因此持續接受治療來控制症狀是重要的目標。治療膀胱過動症的藥物可分為毒蕈鹼拮抗劑和β3腎上腺素受體致效劑，後者目前只有mirabegron可被使用，台灣在2015年將此藥品納入健保給付範圍。而在mirabegron給付後，探討台灣膀胱過動症藥物流行病學的文獻十分缺乏。因此，將執行一項回溯性研究，以評估膀胱過動症的治療分布、比較不同藥物的服藥持續性及依順性，最後比較使用藥物治療膀胱過動症的依順性，是否影響泌尿道感染的風險。
研究方法:
本研究使用台灣全民健保資料庫的就醫資料 (2013年至2017年)，研究的目標族群為具有膀胱過動症診斷的病人，研究藥物涵蓋flavoxate、oxybutynin、propiverine、solifenacin、tolterodine、trospium 和 mirabegron。持續性和依順性將評估治療時間、藥物覆蓋天數的比例及停藥的風險。連續型變項包含治療時間及藥物覆蓋天數的比例以平均值 (標準差)及中位數 (四分位距)呈現，停藥及泌尿道感染的風險將以COX 回歸分析。
研究結果:
本研究納入了35,316位具有膀胱過動症診斷的病人，其中24,623 (69.72%) 曾經使用過研究藥物，10,693 (32.13%) 位沒有使用研究藥物的紀錄。在台灣2014年至2016年，膀胱過動症的盛行率分別為每一萬人中有6.84、7.58及10.97人。針對有用藥的族群，共有22,471位病人符合依順性分析的條件，其中平均治療天數為49.55 (80.86)天，中位數為14.0 (7.0-52.0)天，用藥天數最短的藥物是trospium，最長的是mirabegron，其次為solifenacin和tolterodine。至於覆蓋天數的比例，平均數為0.168 (0.245)，中位數為0.058 (0.019-0.200)。而停藥風險，經過多變項的校正，相較於mirabegron，flavoxate有4.618倍的風險，風險高低依序為 trospium、oxybutynin、propiverine、tolterodine (p值皆<0.0001)，而solifenacin 具有1.053 倍的風險 (p值=0.1644)。至於依順性是否影響泌尿道感染的風險，不論性別及先前是否有泌尿道感染，長期使用研究藥物並不會增加泌尿道感染的風險。
研究結論:
台灣膀胱過動症的盛行率正逐年增加，根據治療分布結果顯示，oxybutynin, trospium和mirabegron的使用量也逐年上升。Mirabegron在服藥依順性的比較中，明顯優於其他藥物，而其次為solifenacin，並且在停藥風險、治療天數及藥物覆蓋比例的指標中，和mirabegron的比較皆沒有差異。至於長期使用研究藥物並不會增加輕度或是嚴重泌尿道感染的風險。

關鍵字

膀胱過動症 ； 藥物流行病學 ； 抗膽鹼藥物 ； mirabegron ； 持續性 ； 依順性

並列摘要

Background and Objectives:
Overactive bladder (OAB) is a complex syndrome, including urgency, nocturia, and frequency, or incontinence. Although it is a non-fatal disease, however, the symptoms can be curable rarely. Continuous acceptance is an important goal for treatment. Medication for OAB involved anti-muscarinic agents and beta 3-adrenoceptor agonists, which the only mirabegron can be available and covered by National Health Insurance (NHI) in 2015 in Taiwan. After literature review, there was a limited study to survey the pharmacoepidemiology for OAB in Taiwan, especially after mirabegron covered. Therefore, we conducted a nationwide, population-based, retrospective study to evaluate the prevalence, treatment distribution, persistence and adherence, and UTI risk between high and low adherence.
Methods:
The data source was the medical records from 2013.01.01 to 2017.12.31 from National Health Insurance Research Database (NHIRD). The targeted population was the patient diagnosed OAB and targeted drugs were flavoxate, oxybutynin, propiverine, solifenacin, tolterodine, trospium, and mirabegron. Persistence and adherence would be evaluated by treatment duration, proportion of days covered (PDC), and risk of discontinuation. Continuous variables for prevalence, treatment duration, and PDC would be presented by means (standard deviation, SD) and median (Interquartile range, IQR). Risk of discontinuation and UTI would be evaluated by cox regression.
Results:
There were 35,316 OAB population, there were 24,623 (69.72%) drug users and 10,693 (32.13%) non-users. The prevalence was 6.84, 7.58, 10.97 person per 10,000 adults in Taiwan from 2014 to 2016. Among the drug users, there were 22,471 patients involved in persistence analysis. Mean (SD) of continuous use days was 49.55 (80.86) and median (IQR) was 14.0 (7.0-52.0) days. The shortest was trospium and the longest was mirabegron, followed by solifenacin and tolterodine. As for PDC analysis, mean was 0.168 (0.245) and median was 0.058 (0.019-0.200). The risk of discontinuation, flavoxate had 4.618 times compared to mirabegron and followed by trospium, oxybutynin, propiverine, tolterodine (all p-value<0.0001). Solifenacin had 1.053 times without significance in statistics (p-value=0.1644). As for the risk of UTI between high and low adherence, severe and mild UTI didn’t be influenced by targeted drugs for the long-term regardless of UTI history and gender.
Conclusions:
The prevalence of OAB in Taiwan was increasing by the year. The treatment distribution showed the usage amounts of oxybutynin, trospium, and mirabegron were rising. Mirabegron was the best selection in persistence analysis. Solifenacin wasn’t a significant difference with mirabegron in the risk of discontinuation, treatment duration, and PDC analysis. Long-term accepting targeted drugs didn’t increase the risk of severe and mild UTI.

並列關鍵字

overactive bladder ； pharmacoepidemiology ； anti-muscarinic agents ； mirabegron ； persistence ； adherence

參考文獻

1. B.T. Haylen, D. de Ridder, R.M. Freeman, S.E. Swift, B. Berghmans, J. Lee, et al., An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J, 2010. 21(1): 5-26.

2. S. Rahnama’i, Overactive Bladder. International continence society committees, 2018, https://www.ics.org/committees/standardisation/terminologydiscussions/overactivebladder.

3. M.J. Drake, Do we need a new definition of the overactive bladder syndrome? ICI-RS 2013. Neurourol Urodyn, 2014. 33(5): 622-624.

4. C.-C. Lu, Assessment of overactive bladder symptoms in a community-dwelling population using the Taiwanese version of the Overactive Bladder Symptom Score. Incont Pelvic Floor Dysfunct, 2009. 3: 60-61.

5. C.R. Chapple, W. Artibani, L.D. Cardozo, D. Castro-Diaz, M. Craggs, F. Haab, et al., The role of urinary urgency and its measurement in the overactive bladder symptom syndrome: current concepts and future prospects. BJU Int, 2005. 95(3): 335-340.