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作者：Kristina Rebelo  
出處：WebMD醫學新聞

　　【24drs.com】November 3, 2009（加州聖地牙哥訊）－即使是研究者也對這項臨床研究結果感到意外，緩釋型mesalamine（Asacol HD，Procter與Gamnble藥廠）每天使用一次與每天使用兩次的療程，在維持潰瘍性結腸炎（UC）消退上一樣有效。
　　
　　根據目前針對UC進行的最大型研究QDIEM（the QD Dosing Investigation for Efficacy in UC Maintenance），每天使用一次，病患的順應率比較高；這項研究結果發表在美國腸胃科醫學會2009年度科學會議的最新發展座談會上。
　　
　　第一作者與共同研究者，梅約診所醫學院醫學與腸胃科學研究教授，同時也是明尼蘇達羅徹斯特梅約診所腸胃肝膽科副主席的William J. Sandborn醫師在與Medscape腸胃醫學訪談中表示，我們對於這個結果有一點意外，因為緩釋型mesalamine在結腸末端與右大腸釋放上是快速的，因此目前並不清楚這個藥物是否可以一天投予一次。
　　
　　Sandborn博士繼續說道，需要有臨床研究來確認這個問題的解答，而QDIEM研究提供了確切的答案。
　　
　　QDIEM研究中，總共收納1,023位病患，這些病患在進入研究之前，每天使用mesalamine劑量範圍介於1.6至2.4 g之間，都處於疾病消退期（簡易臨床結腸炎活性指標分數低於2分）至少四個月以上。這些病患被隨機分派接受進入研究前維持相同、每天一次或每天兩次的劑量療程，例如，70%的病患每天接受2.4 g的mesalamine 、28%每天接受1.6 g的mesalamine 、2%每天接受2.0 g的mesalamine。
　　
　　試驗的主要終點為，每天一次以及每天兩次的療程，在六個月時維持疾病消退的情況。疾病再發定義為，簡易臨床結腸炎活性指標分數高於5分。沒有疾病再發的病患，則被認為是消退的。
　　
　　疾病消退所需的時間，每天一次和每天兩次的療程是相仿的（危險比值為1.19；95%信賴區間為0.77-1.82）；兩組在嚴重的不良反應與後續因不良反應而退出研究的比例，也是差不多的。
　　
　　Sandborn博士的團隊發現，在維持UC消退方面，以緩釋型mesalamine在劑量範圍1.6~2.4 g之間，每天投予一次（400 mg的錠劑）與每天兩次的劑量療程一樣有效。
　　
　　Sandborn博士表示，臨床醫師們應該使用這些數據作為投予緩釋型mesalamine用於維持療法，劑量達每天2.4 g的基礎。
　　
　　Sandborn博士表示，我們看到三個月間服藥順從性有顯著差異，但超過三個月後並無顯著差異。然而，當我們問病患是否願意每天服藥一次，絕大多數（58%）的病患都說他們在12個月時，對每日一次的療程非常滿意。
　　
　　美國腸胃科醫學會教育事務委員會主席、俄亥俄州克里夫蘭診所消化疾病中心腸胃科成員Jean-Paul Achkar醫師、FACG，在與Medscape腸胃科學訪談時宣稱，這是2009年年會中最重要的研究。表面上，這可能聽起來沒那麼有趣，但病患的順從性是個重要議題；我們曉得病患未依照醫囑服藥，有這麼一個簡化的、每天一次的療程，很可能因而改善病患的順從性。
　　
　　他附帶表示，美國食品藥物管理局（FDA）目前已經核准mesalamine每次兩顆、一天三次的劑量療程。許多執業醫師認為這並不切實際，許多醫師已經把這改為每天兩次，而這項研究提供了進一步的證據，我們可以進一步退回到每天投予一次。
　　
　　這項研究接受Procter與Gamble藥廠研究贊助，Asacol的製造廠商。Sandborn博士是Procter與Gamble藥廠的顧問。Achkar博士表示已無相關資金上的往來。

Once-Daily Mesalamine as Effective as Twice-Daily Treatment for Maintenance of Remission in UC

By Kristina Rebelo
Medscape Medical News

November 3, 2009 (San Diego, California) — In clinical trial results that surprised even the investigators, delayed-release mesalamine (Asacol HD, Procter Gamble) once a day was as effective as a twice-a-day regimen in keeping ulcerative colitis (UC) inactive.

Once-a-day dosing also made for much higher compliance rates in patients, according to findings of the QD Dosing Investigation for Efficacy in UC Maintenance (QDIEM) study, the largest UC study undertaken to date. Results were announced here at the American College of Gastroenterology 2009 Annual Scientific Meeting in a late-breaking session.

"We were a little surprised at the results since delayed-release mesalamine is more of a bolus in the terminal ileum and right colon, so it wasn't clear that it could be administered once daily," first author and coinvestigator William J. Sandborn, MD, professor of medicine and gastrointestinal research, Mayo Clinic College of Medicine, and vice chairman, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, commented in an interview with Medscape Gastroenterology.

Dr. Sandborn continued, "A clinical trial was required to determine the answer to this question, and the QDIEM trial provided a definitive answer."

There were 1023 patients in QDIEM who had been in remission for at least 4 months before the start of the study (Simple Clinical Colitis Activity Index score < 2 points) on mesalamine doses ranging from 1.6 to 2.4 g a day. Patients were randomly assigned to either a once- or twice-daily dosing regimen at the same total daily dose that the patient had been maintained on before study entry, such that 70% received 2.4 g mesalamine daily, 28% received 1.6 g mesalamine daily, and 2% received 2.0 g mesalamine daily.

The primary endpoint was maintenance of remission at 6 months on a once-daily dosing regimen compared with twice-daily dosing. Relapse was defined as an Simple Clinical Colitis Activity Index score higher than 5 points. Patients who had not relapsed were considered to be in remission.

The time to relapse was similar between once-daily and twice-daily dosing (hazard ratio, 1.19; 95% confidence interval, 0.77 – 1.82). Serious adverse reactions and subsequent trial withdrawals resulting from adverse events were similar between the 2 groups.

Dr. Sanborn's team found that once-daily dosing with delayed-release mesalamine at doses of 1.6 to 2.4 g daily (administered in 400-mg tablets) was as effective as twice-daily dosing for maintenance of remission in patients with UC.

"Clinicians could use these data as a basis for administering delayed-release mesalamine as maintenance therapy at doses up to 2.4 g a day," said Dr. Sandborn.

"We saw significant differences in medication adherence up through 3 months, but not beyond," Dr. Sandborn noted. "However, when we asked patients if they preferred to take their medication once daily, a majority (58%) said they were extremely satisfied at month 12 with once-daily dosing."

"This was the most important study to come out of the 2009 [meeting]," asserted Jean-Paul Achkar, MD, FACG, chair of the educational affairs committee of the American College of Gastroenterology and a member of the Department of Gastroenterology at the Digestive Disease Center, The Cleveland Clinic, Ohio, in an interview with Medscape Gastroenterology: "On the surface, this may not sound very exciting, but patient adherence had been an important issue; we realize that patients don't take medications as they should, so having a simplified regimen of once-daily dosing is likely to improve compliance."

He added: "Currently, the US Food and Drug Administration has approved mesalamine at a dose of 2 pills, 3 times a day. Many of us in practice thought that was not practical, and many of us have cut down that dose to 2 divided doses, and this study is further evidence that we can back off further and go to once-daily dosing."

The study received research support from Procter Gamble Pharmaceuticals, the maker of Asacol. Dr. Sandborn is a consultant for Procter & Gamble Pharmaceuticals. Dr. Achkar has disclosed no relevant financial relationships.

American College of Gastroenterology 2009 Annual Scientific Meeting: Abstract 39. Presented October 27, 2009.