台灣地區改變多發性硬化症病程的第一線治療藥物對於復發再住院率的影響

The Impact of Changing the Course of Multiple Sclerosis Treatment with First-Line DMT Medications on Hospital Readmission Rate in Taiwan

古鎮睿(Chen-Jui Ku)

指導教授 ： 柯黃盛

高雄醫學大學/藥學院/藥學系碩士班/碩士(2016年)

摘要

研究背景：
多發性硬化症（multiple sclerosis, MS）在台灣屬於罕見疾病，此病是一種中樞神經系統（central nervous system）發炎性脫髓鞘疾病，由於中樞神經系統反覆出現發炎反應，而造成神經髓鞘脫失。治療這類疾病以改變病程的長期治療（disease modifying therapy, DMT）用藥為主，而這當中又以免疫調節劑（immunomodulator）為要。

研究目的：
本研究主要分析探討interferon β：可分為 interferon β-1a（如 Rebif®）和 interferon β-1b（如 Betaferon®），以及 glatiramer acetate（如 Copaxone®）這三種改變病程藥物(Disease modifying drug,DMD)之治療為主的第一線藥物與多發性硬化症年復發率之相關性。

研究方法：
本研究設計是採回溯性研究（Retrospective study），而研究架構乃參考MS相關之文獻而成，以台灣地區MS疾病復發率及用藥、國內外盛行率的比較以及醫療資源耗用的影響；並參用國家衛生研究院所提供之台灣地區健保資料庫（特定多發性硬化症2007-2009資料庫全人檔），且以Rebif、 Betaferon及Copaxone作為用藥種類之分析。

研究結果：
第一部份：
台灣男性在2007-2009年，其多發性硬化症標準化盛行率分別為3.15、3.25、3.47，女性分別為9.41、10.46及10.79，多發性硬化症國人標準化盛行率女性高於男性。另外，國人女性盛行率也超過衛生福利部國民健康署所定義之罕病法對於罕見疾病的定義為：盛行率在萬分之一以下。
第二部分：
處方藥物分布比例以Rebif為最高（59.75％）其2007-2009年復發率(年因多發性硬化症為例)分別為(1.22/1.27/1.17)，其他依序為Betaferon（27.63％）2007-2009年復發率分別為(1.10/1.08/1.43)、Copaxone（17.01％）其2007-2009年復發率分別為(1.66/2.12/1.75)。而復發率定義為：當年因多發性硬化症再次住院一次以上計算。
第三部分：
病例組（Rebif、Betaferon、Copaxone）與對照組(本組為無使用藥物組，並且其定義為雖然沒有使用DMD，但是有使用口服類固醇或是其他藥物)無論在核磁共振影像(Magnetic Resonance Imaging, MRI)次數、門診次數、門診費用、住院次數、住院費用、住院天數皆達到統計上之差異（P ﹤0.0001)

研究結論：
目前多發性硬化症的長期治療還是以第一線 DMT為主，雖然第二線的藥物越來越多，但是因為國內上市時間僅有短短三年時間，所以在使用上仍需格外小心謹慎。雖然本研究的結果顯示各病例組以及與對照組在年復發率、MRI使用次數、整體醫療費用上相比有明顯差異，但是因為無法得知是否和病患的用藥醫囑性有關（有無併用中草藥治療或另類療法），所以仍然需進一步探討。

關鍵字

多發性硬化症 ； 改變病程的長期治療 ； 免疫調節劑 ； 核磁共振影像 ； 年復發率

並列摘要

Backgrounds
Multiple sclerosis (MS) is considered an uncommon and rare disease in Taiwan. MS is a chronic neuroimmunologic disorder and a demyelinating disease of the central nervous system that results in damage to the protective covering of the peripheral nerves (myelin sheath) and causes the loss of myelin (demyelination) due to this repeated inflammatory demyelinating condition. Disease-modifying therapies (DMTs) are a long-term comprehensive care for the treatment of people with MS. Using immunomodulatory agents (immunomodulators) is the main therapeutic strategy for managing the frequency of MS relapses.

Objective
There are three main disease-modifying drugs (DMDs) used as first-line treatments for MS. They are glatiramer acetate (Copaxone®) and interferon beta preparations, which are divided into interferon β-1a (Rebif®) and interferon β-1b (Betaferon®). The purpose of this study is to analyze and discuss the correlations of the annual MS relapse rate and the changing courses of treatment between three DMDs.

Methods
This was a multicenter and retrospective study that used MS literature citations as baseline references. This study compared annual MS relapse rate as a primary efficacy endpoint and the usage of the medications in Taiwan. The study determined the impact of the prevalence rate and the consumption of the medical resources between Taiwan and other countries in line with the adoption of specific MS 2007-2009 holistic file data from National Health Insurance Research Database provided by National Health Research Institutes. A comprehensive analysis of the types of medications such as Betaferon®, Copaxone® and Rebif® are also included in this study.

Results
Part I:
The prevalence of people with female MS patients in Taiwan regardless of gender is higher than the prevalence of MS by the world standards. In addition, the Taiwan Ministry of Health and Welfare worked in conjunction with the Taiwan Health Promotion Administration to set a standard definition of rare diseases as the prevalence rate of 1/10,000 or less. The prevalence of women with MS in Taiwan also exceeded the overall Taiwanese standard.

Part II:
Rebif® had the highest dispensing percentage of all three DMDs. The proportion of prescription drug distribution of Rebif® was 59.75% and its 2007--2009 annual relapse rate calculated according to the annual number of hospitalizations was 1.22 / 1.27 / 1.17. The proportion of prescription drug distribution of Betaferon® was 27.63% and its 2007 - 2009 annual relapse rate calculated according to the annual number of hospitalizations was 1.10 / 1.08 / 1.43. The proportion of prescription drug distribution of Copaxone® was 17.01% and its 2007--2009 annual relapse rate calculated according to the annual number of hospitalizations was 1.66 / 2.12 / 1.75.

Part III:
The case group (Betaferon®, Copaxone® and Rebif®) and the control group both achieved the statistical difference (P <0.0001) based on the number of magnetic resonance imaging (MRI) received, the number of hospitalizations, the associated costs for these hospital stays, the number of days spent per hospitalization, the number of physician office visits, and the costs of outpatient care.

Conclusions
At the present time, using the first‐line DMT medications is still the gold standard for the long‐term treatment of MS patients. There are more second‐line medications being developed and used for treating and managing MS in Taiwan. These medications were introduced to Taiwanese patients for mere three years. The medical practitioners should administer second‐line DMDs with extra caution and monitor patients carefully because the effectiveness of these medications and any adverse side effects have not been fully determined.
The results of this retrospective study showed that each case group and the control group reflected significant differences in annual relapse rate, MRI usage, and overall healthcare costs. However, this study could not verify the rate of adherence to DMTs among MS patients and could not identify patients who took herbal supplements or received other alternative therapies along with DMTs. Therefore, additional analysis of the components of the DMTs needs to be further explored.

並列關鍵字

Multiple sclerosis ； Disease-modifying therapies ； Immunomodulators ； Magnetic resonance imaging ； Annual relapse rate

參考文獻

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