Thiopurines類藥物可以改善發炎性腸道疾病患者的生活品質
作者：Nancy Fowler Larson
出處：WebMD醫學新聞
March 3, 2010 — 根據一項於3月2日線上發表在BMC腸胃醫學期刊的研究結果，接受thiopurine類藥物治療的發炎性腸道疾病（IBD）患者，可以體驗到生活品質的改善。
主要作者，來自西班牙瓦倫西瓦La Fe醫院腸胃科的Guillermo Bastida醫師在一篇新聞稿中表示，有良好的證據顯示，thiopurines類藥物不論是降低或是維持IBD消退都有其效果；這些藥物對於生活品質的效果一直備受關注，然而，有少數報告顯示這些藥物會讓病患覺得他們的生活在接受藥物治療時變得更加辛苦。
Thiopurines類藥物是一種在體內與許多食物中發現的自然物質。在這項研究之前，thiopurines類藥物治療對罹患IBD病患並沒有足夠與健康有關生活品質（HRQoL）影響之相關數據。這項研究的目的在於評估thiopurines類藥物對這些病患的HRQoL短期與長期效應，以及探索其效應在臨床與生物方面的關係。
這項研究前瞻性地針對一家西班牙醫院的92位病患，這些病患被診斷罹患兩種IBD的其中一種：克隆氏疾病或是發炎性腸道疾病。這些病患都接受azathioprine治療，許多thiopurines類藥物中的一種。每天50 mg的起始劑量在第一個月增加到2.5 mg/kg，也就是目標劑量。許多對azathiopurine無法耐受的病患改接受6-mercaptopurine治療。12位病患中有7位因為毒性而停止使用這個藥物。
每位受試者在試驗前、6個月後、1年時接受生活品質問卷評估，使用醫療預後研究36項短版健康調查（SF-36）以及發炎性腸道疾病問卷（IBDQ）。SF-36問卷包括8個部分，包括身體功能、情緒問題、精神健康、以及整體健康感受。該問卷分數以0（最差狀態）到100（最好狀態）百分比表示。
IBDQ分為5個部分：分別為腸胃道症狀、系統性症狀、功能受損、社交功能受損以及情緒功能。以7分李克氏量表評分，7分代表最佳功能。
【隨著治療時間繼續改善】
在試驗前，平均IBDQ分數為4.6分（範圍從2.31分到6.84分），在試驗族群的這5個部分都比西班牙一般大眾差。SF-36問卷結果顯示所有8個部分的生活品質都是較差的。
但隨著試驗進行，這兩項問卷的評量結果都出現進步。在6個月時，IBDQ分數中位數顯著改善（5.8分，範圍為1.58-6.97分），其他5個IBDQ部分也都是同樣的結果。SF-36問卷的8個部分也都看到顯著進步。在12個月時，IBDQ分數中位數為6.1分（範圍從2.7分到6.98分）；相較於試驗前與6個月的評估，所有部分都是恢復的。SF-36問卷所有部分分數都有相對應的增加。
Bastida醫師與其同事們表示，我們的研究結果顯示，在開始使用thiopurines類藥物之前，罹患IBD患者牽涉到HRQoL主要部分的認知健康狀態顯著變差。除此之外，更重要的是，這項研究提供了azathiopurines類藥物與6-mercaptopurine在IBD患者所有HRQoL部分正面與長期影響的證據。
美洲克隆氏症與腸炎基金會科學顧問主委、北卡羅萊納州立大學教堂山分校的R. Balfour Sartor醫師向Medscape腸胃醫學表示，這項研究是獨特的，且加強了他的臨床經驗。但是這項研究有幾項缺失，包括受試者個體多重差異。
Sartor醫師指出，這項研究中有數種誘發藥物。某些病患有術後再發，而其他則非手術病患。因此，在這多樣性高的群體中是有許多限制的，而且也沒有控制組；此外，並未與其他潛在維持性治療進行比較。
研究作者們表示，之後的研究應該評估提早導入thiopurines類藥物對IBD進程的影響，以及該藥物對生活品質的長期效應。他們也指出接受thiopurines類藥物治療病患，需要更多更密集的理學檢查。
Bastida醫師與其同事們寫到，在這項研究中，我們並未常規進行內視鏡檢查。另一個重要問題應該在未來的研究提到的是HRQoL的意義以及azathiopurine引起黏膜癒合的自然史。
UCB-Pharma贊助這項研究。研究作者們表示已無相關資金上的往來。
Thiopurines Improve Quality of Life for Patients With Inflammatory Bowel Disease
By Nancy Fowler Larson
Medscape Medical News
March 3, 2010 — Patients with inflammatory bowel disease (IBD) who undergo thiopurine therapy experience improved quality of life, according to a study published online March 2 in BMC Gastroenterology.
"The efficacy of thiopurines in the scenarios in which they are prescribed, either to induce or to maintain remission in IBD, is well proven," said lead author Guillermo Bastida, MD, from the gastroenterology unit, La Fe Hospital, Valencia, Spain, in a news release. "Their effect on quality of life has been a cause for concern however, with some reports suggesting that they can cause patients to perceive their lives as being more difficult while under treatment."
Thiopurines are natural substances found in the body and most foods. Before the study, adequate data did not exist on the effect of thiopurine treatment on health-related quality of life (HRQoL) in patients with IBD. The goal of the study was to assess the long- and short-term effect of thiopurines on HRQoL in these patients and to explore the association between the clinical and biological aspects of its effects.
Researchers prospectively studied 92 patients in a single Spanish hospital who were diagnosed with 1 of 2 types of IBD: Crohn's disease or ulcerative colitis. All were treated with azathioprine — one of several thiopurines. An initial dose of 50 mg daily was increased within the first month to 2.5 mg/kg, the target dose. A dozen patients with azathioprine intolerance received 6-mercaptopurine treatment. Seven of the 12 patients were taken off that drug because of its toxicity.
Each participant was evaluated for quality of life at the study's onset, at 6 months, and at 1 year, using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). The SF-36 consists of 8 dimensions including physical function, emotional problems, mental health, and general health perception. Its scores were shown as a percentage on a scale of 0 (least favorable status) to 100 (most favorable).
The IBDQ is divided into 5 dimensions: bowel symptoms, systemic symptoms, functional impairment, social impairment, and emotional function. Scoring is on a 7-point Likert scale, with 7 describing the best function.
Improvements Continue Over Time
At the beginning of the study, the mean baseline IBDQ score was 4.6 (range, 2.31 - 6.84), with poorer results in all 5 categories for the study population compared with the general population in Spain. The SF-36 results showed a worse quality of life in all 8 sections.
Both measures showed improvements as the study progressed. At 6 months the median IBDQ score (5.8; range, 1.58 - 6.97) showed marked improvement, as did all 5 IBDQ dimensions. Each of the 8 SF-36 categories also saw significant upgrades. At 12 months, the median IBDQ score was 6.1 (range, 2.7 - 6.98), with recovery in all areas compared with baseline and 6-month evaluations. The SF-36 produced a comparable increase in all categories.
"Our study shows that before initiating thiopurines, patients with IBD have greatly impaired perceived health status involving the majority of the aspects of HRQoL," write Dr. Bastida and colleagues. "Furthermore, and more importantly, this study provides evidence of the positive and long-lasting impact of azathioprine and 6-mercaptopurine on all dimensions of HRQoL in patients with IBD."
R. Balfour Sartor, MD, from the University of North Carolina, Chapel Hill, and chief scientific advisor of the Crohn's and Colitis Foundation of America, told Medscape Gastroenterology that the study is unique, and it reinforces his clinical experience. But Dr. Sartor also noted several drawbacks, including multiple differences among the participants' individual cases.
"There were variable-inducing drugs. Some patients had postoperative recurrences and others were nonsurgical," Dr. Sartor said. "So clearly there are limitations in the heterogeneous population, as well as a lack of a control group; you're not comparing it to the other potential maintenance therapies."
Subsequent studies should evaluate the introduction of thiopurines earlier in the progression of IBD and the drug's longer-term effect on quality of life, the study authors note. They also point out the need for more intense physical examination of patients undergoing thiopurine therapy.
"In this study, we did not routinely perform endoscopy," Dr. Bastida and colleagues write. "Another important issue that should be addressed in future investigations is the implications on HRQoL and in the natural history of azathioprine-induced mucosal healing."
UCB-Pharma supported the study. The study authors have disclosed no relevant financial relationships.
BMC Gastroenterol. Published online March 2, 2010.
