作者：Deborah Brauser
出處：WebMD醫學新聞
October 10, 2008(佛州奧蘭多) — 根據一項大型多中心第2期試驗的次級分析研究，Rifaximin可以顯著改善腹瀉型腸躁症(irritable bowel syndrome and diarrhea，IBS-D)病患的生活品質。
在原本的四週雙盲試驗中，388名成人(106名男性、282名女性)診斷有IBS-D (根據羅馬準則第二版)，他們於美國的75個研究中心進行治療。研究人員給予他們每天兩次的rifaximin 550 mg (n= 191)或者安慰劑(n= 197)，為期14天；之後，兩組的所有病患都接受14天的安慰劑。試驗結束時的結果顯示，相較於安慰劑組，rifaximin明顯改善IBS症狀。
之後進行次級分析研究，以評估此藥物在同樣劑量下對於病患生活品質(QOL)的影響；密西根大學健康系統的醫學教授William Chey醫師將此第2b期試驗的結果發表在美國腸胃道學會(ACG)2008年科學座談會與畢業後課程的海報。
在發表時，Chey醫師表示，最近的這些資料來自2b期臨床試驗，與其他進行中的試驗認為rifaximin對IBS病患可以提供臨床好處，至於對於生活品質的效果則無報告；基於該症狀對於生活品質有所影響，這的確是此病最重要的問題之一。
他進一步表示，這是人們常問的問題，如果可以改善症狀最好，但接著，是否可實際改善生活品質呢？這個生活品質分析是設計良好的隨機控制試驗，且使用正式的工具進行分析，結果顯示，相較於安慰劑，rifaximin對生活品質有明顯的幫助。
當被問到如何定義生活品質時，Chey 醫師表示，他們使用腸躁症生活品質問卷(IBS-QOL)，那是一個有34個問題的調查表，已經證實可以準確評估生活品質且對改變有敏感度，因此，它是一個可以幫助醫師在提供診斷介入前後的合理工具。
根據Chey醫師的發表，在開始時和第四週時填寫IBS-QOL，每一次的給分從1分(完全沒有)到5分(強烈或者非常)，這些回應轉為0-100分(分數越高表示QOL越佳)，並計算整體的QOL分數和8個次量表分數；此外，也評估副作用(adverse events (AEs))。
四週研究結束時，相較於安慰劑(15.8; P= .02)，rifaximin治療顯著改善病患的QOL分數(20.4)；此外，相較於安慰劑，治療組的整體QOL改善了28.7%。
另外，相較於安慰劑，rifaximin組在以下指標都有明顯改善(P< .05)：煩躁(25.2%)、身體心象(37.4%)、健康憂慮(30.6%)、社會反應(31.6%)與關係(39.5%)。
兩組發生AEs的報告相似，大部份屬於輕微到中度反應。
發表後，Chey醫師向Medscape Gastroenterology 表示，這些結果實際報告出rifaximin不只讓個人症狀更好，也改善了疾病相關的生活品質。
當被問到對於未來的看法時，Chey醫師回覆，下一步驟是從兩個進行中的大型第3期臨床試驗釐清資料；坦白說，我們在第2期試驗資料中看到很多藥物效果不錯，實際上，更大型且方法更嚴謹之第3期臨床試驗的證據更有效。
McMaster大學醫學中心胃腸科名譽專家、醫學講座、Alexander Ford醫師向Medscape Gastroenterology表示，整體來說，此試驗是個不錯的研究；Ford醫師未參與該試驗；他指出，這個試驗設計不錯且有不少病患，顯然地，它是一個隨機安慰劑控制試驗，因此它的證據力相當高。
他進一步表示，這些病患的生活品質改善比使用安慰劑者多25%以上，這對於IBS病患相當鼓舞且很有趣。
當被問到是否有任何顧慮時，Ford醫師表示，指出症狀的影響是有趣的，顯然的，真正的顧慮在於這是個四週的追蹤，因此雖然有令人鼓舞的改善，但長久以往是否依舊有效，則還有爭議；我會注意這兩組病患的長期追蹤與更多的症狀資料。
本研究由Salix Pharmaceuticals資助。 Chey醫師任職於Salix發言部門。Ford 醫師宣稱沒有相關資金上的往來。
美國腸胃道學會2008年科學會與畢業後課程：海報P-691。發表於2008年10月6日。
Rifaximin Appears to Improve Quality of Life in Patients With IBS-D
By Deborah Brauser
Medscape Medical News
October 10, 2008 (Orlando, Florida) — Rifaximin may significantly improve quality-of-life symptoms in patients with irritable bowel syndrome and diarrhea (IBS-D), according to a secondary-analysis study evaluating data from a large multicenter phase?2 trial.
In the original 4-week double-blind trial, 388 adult patients (106 men, 282 women) diagnosed with IBS-D (according to Rome?II criteria) were enrolled and treated at 75 study centers throughout the United States. They were given either a twice-daily dose of rifaximin 550?mg (n?= 191) or placebo (n?= 197) for 14 days. Then, all patients in both groups received placebo only for an additional 14 days. Results at the end of that trial showed significantly improved IBS symptoms with rifaximin, compared with placebo.
A secondary-analysis study was then designed to evaluate the efficacy of the drug's same dosage in improving quality of life (QOL) in these same patients. The results from this phase?2b study were presented in a poster session here at the American College of Gastroenterology (ACG) 2008 Annual Scientific Meeting and Postgraduate Course by William Chey, MD, professor of medicine at the University of Michigan Health System, in Ann Arbor.
During his presentation, Dr. Chey said that although "there are recent data from a phase?2b clinical trial, as well as other preceding trials, that suggest that rifaximin offers clinical benefits for patients with IBS, there have been no data reported on the effect of the drug on quality of life. And given the fact that the symptoms have a profound impact on quality of life, that's really 1 of the most dramatic effects of the illness."
He continued: "It's a natural question then to ask. It's great that it makes the symptoms better, but in terms of the next step, does it really improve quality of life? This analysis was a rigorously designed randomized controlled trial that assessed quality of life. And using a formal instrument, it shows clear benefits on quality of life for rifaximin, compared with placebo."
When asked how his research team defined quality of life, Dr. Chey said that they used the Irritable Bowel Syndrome Quality-of-Life Instrument (IBS-QOL). "This is a 34-item survey instrument that's been validated as an accurate means of assessing quality of life and appears to be sensitive to change. So it's a reasonable tool to use to look at before and after [clinicians] offer some kind of a therapeutic intervention."
According to Dr. Chey's presentation, the IBS-QOL was filled out at baseline and at week 4, and each item was scored on a scale from 1 (not at all) to 5 (extremely or a great deal). These responses were then converted to a scale ranging from 0 to 100 (higher scores indicating better QOL) and used to compute the overall QOL score and 8 subscale scores. In addition, adverse events (AEs) were evaluated.
At the end of the 4-week study, treatment with rifaximin resulted in significantly greater improvement from baseline in overall patient QOL scores (20.4), compared with placebo (15.8; P?= .02). Plus, there was a 28.7% improvement in overall QOL in the treatment group, compared with placebo.
In addition, the rifaximin group showed significantly greater improvements over placebo from baseline in the subscale scores for dysphoria (25.2%), body image (37.4%), health worry (30.6%), social reaction (31.6%), and relationships (39.5%), compared with placebo (P?< .05).
The incidence of reported AEs was similar in both groups, with most reported as being of mild to moderate intensity.
After the presentation, Dr. Chey told Medscape Gastroenterology that these results "just really support the message that [rifaximin] not only makes the individual symptoms better, but it also improves disease-specific quality of life."
When asked what he predicts for the future, Dr. Chey replied: "The next step is clearly data from the 2 large ongoing phase?3 clinical trials. Let's be honest, we've seen lots of drugs with very promising phase?2 data. And really, the proof of the pudding is going to be in those much larger methodologically rigorous phase?3 clinical trials."
Alexander Ford, MD, lecturer in medicine and honorary specialist registrar in gastroenterology at McMaster University Medical Centre, in Hamilton, Ontario, told Medscape Gastroenterology that overall, "this trial looks like a great study." Dr. Ford was not involved in the trial. "It's very well designed with a large number of patients. And obviously, it's a randomized placebo-controlled trial, so it's on the highest levels of evidence that we have."
He continued: "The quality-of-life scores improved by more than 25% over those patients who received placebo, which is obviously very interesting and encouraging for people with IBS."
When asked if he had any concerns, Dr. Ford replied: "It would be interesting to note what the effect on symptoms was. And the caveat really is that, obviously, this was a 4-week follow-up. So although the improvement is encouraging, whether or not that would continue in the long term is up for debate, I guess. I'd like to see a longer follow-up and more symptom data from both groups of patients."
This study was funded by Salix Pharmaceuticals. Dr. Chey has been on the Salix Speakers Bureau. Dr. Ford has disclosed no relevant financial relationships.
American College of Gastroenterology (ACG) 2008 Annual Scientific Meeting and Postgraduate Course: Poster P-691. Presented October 6, 2008.
[ 本帖最後由 goodcat1111 於 2008-10-20 23:15 編輯 ] |
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