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Tegaserod for the treatment of irritable bowel syndrome and chronic constipation

  • Review
  • Intervention

Authors


Abstract

Background

IBS is a complex disorder that encompasses a wide profile of symptoms. The symptoms of chronic constipation frequently resemble those of constipation-predominant IBS. Current drug treatments for irritable bowel syndrome (IBS) are of limited value. Many target specific symptoms only. Tegaserod, a 5HT4 partial agonist, represents a novel mechanism of action in the treatment of IBS and chronic constipation.

Objectives

The objective of this review was to evaluate the efficacy and tolerability of tegaserod for the treatment of IBS and chronic constipation in adults and adolescents aged 12 years and above.

Search methods

MEDLINE 1966-December 2006 and EMBASE 1980 to December 2006 were searched. The text and key words used included "tegaserod", "HTF 919", "irritable bowel", "constipation" and "colonic diseases, functional". The Cochrane Central Register of Controlled Trials, and the Inflammatory Bowel Disease Review Group Specialized Trials Register were also searched. Searches stopped on 15th December 2006. Relevant articles were retrieved, and their reference lists were also reviewed.

Selection criteria

Randomised or quasi-randomised controlled trials comparing tegaserod with placebo, no treatment or any other intervention (pharmacological or non-pharmacological) in subjects aged 12 years and above with a diagnosis of IBS or chronic constipation, focusing on clinical endpoints were considered for review.

Data collection and analysis

Study inclusion and exclusion, data extraction and quality assessment was undertaken by two authors independently. Meta-analysis was performed where study populations, designs, outcomes, and statistical reporting allowed combination of data in a valid way, using the summary statistics relative risk for dichotomous data and weighted mean difference for continuous data, both with 95% CI. Thirteen short-term placebo-controlled studies fulfilled the inclusion criteria. These were predominantly conducted in women. Ten studies evaluated the efficacy of tegaserod on global gastrointestinal (GI) symptoms in patients with constipation-predominant IBS (C-IBS). One small study evaluated safety in patients with diarrhoea-predominant IBS. Two studies evaluated the effectiveness of tegaserod for the treatment of chronic constipation.

Main results

In patients with C-IBS, the relative risk (RR) of being a responder in terms of global relief of GI symptoms during the last 4 weeks of treatment was significantly higher with both tegaserod 12 mg and 4 mg doses compared with placebo. Although the pooled results indicate statistically significant benefit with tegaserod, the a priori minimal clinically important differences set in two of three studies were not reached. The responder rate for this endpoint was also higher when considered for the first 4 weeks of treatment (tegaserod 12 mg only). Tegaserod did not significantly improve the patients' individual symptoms of abdominal pain and discomfort although bowel habit showed a statistically significant improvement with tegaserod 4 mg and there was a non-significant trend in this outcome in favour of tegaserod 12 mg. In patients with chronic constipation, the RR of being a responder in terms of complete spontaneous bowel movements per week with tegaserod 12 mg was 1.54 (95% CI 1.35 to 1.75), WMD for this endpoint compared with placebo 0.6 (95% CI 0.42 to 0.78). Differences between tegaserod and placebo in increases in frequency of bowel movements were small (less than one per week). The proportion of patients with either diagnosis who experienced diarrhea was significantly higher in the tegaserod 12 mg group compared with placebo (RR 2.80, 95% CI 2.13 to 3.68), with a number needed to harm (NNH) of 20. Effects of tegaserod on GI symptoms such as bloating, stool consistency, and straining were not consistent across the studies.

Authors' conclusions

Tegaserod appears to improve the overall symptomatology of IBS, and the frequency of bowel movements in those with chronic constipation. The clinical importance of these modest improvements is not clear. There are currently few data on its effect on quality of life. In addition, more information is needed about its efficacy in men. It would also be of interest to know whether treatment with tegaserod leads either directly, or indirectly, to changes in visceral sensitivity or psychopathology, which are also considered important in the pathophysiology of these conditions.

摘要

背景

Tegaserod對於腸躁症和慢性便秘的治療

腸躁症(IBS)是涵括廣泛症狀的一種複雜性疾病。慢性便秘的症狀經常類似於那些便秘型的躁腸症。目前的藥物治療腸躁症是有限的。許多的治療只針對特異的症狀。一種部分促效劑,代表著一種新的機制作用在治療腸躁症和慢性便秘。

目標

本回顧的目的是評估tegaserod對於治療成年人和青少年12歲及以上腸躁症和慢性便秘的療效和耐受性

搜尋策略

檢索資料包括MEDLINE 1996年到2006年12月和EMBASE 1980年到2006年12月使用的搜尋文字和關鍵詞包括tegaserod,HTF 919,irritable bowel,constipation和colonic disease, functional。我們同時也搜尋The Cochrane Central Register Central Register of Controlled Trials 和the Inflammatory Bowel Disease Review Group Specialized Trials Reigster等資料庫。搜尋的時間直到2006年十二月十五日。檢索相關文章,同時也進行了審查他們的參考文獻目錄。

選擇標準

考慮回顧的隨機或半隨機對照試驗為比較tegaserod與安慰劑,不治療或任何其他處置(藥物或非藥物)在12歲及以上的病人被診斷為腸躁症或慢性便秘並且重點在臨床最終結果。

資料收集與分析

兩位作者獨立地進行研究納入和排除,資料提取和品質評估。綜合資料分析以研究族群,設計,成果,和統計報告能夠利用一個有效的方式結合數據進行,使用摘要統計方法二分類數據以relative risk表示而連續性數據以加權平均差異表示,兩者皆含帶95%CI。13個短期安慰劑對照研究符合納入標準。這些研究主要是在婦女進行的。10個研究評估tegaserod療效為針對便秘型腸躁症的患者全胃腸道(GI)的症狀。一個小型研究在腹瀉型腸躁症患者的安全性。兩份研究報告評估tegaserod對於治療慢性便秘的有效性。

主要結論

在C  IBS的患者,相對危險度(RR)為反應在過去4週的治療胃腸道症狀大致減輕的現象,與安慰劑相比12毫克和4毫克劑量tegaserod顯著較高。雖然匯集統計結果表示,統計學上tegaserod顯著有益,三個研究中有兩個並沒有達到在臨床上重要的輕微差異現象。當考慮前4週tegaserod的治療(tegaserpd僅12毫克),tegaserod在此端點反應率也較高tegaserod並沒有顯著改善患者腹部疼痛和不適的個別症狀,雖然使用4毫克tegarserod大便習慣表現出顯著性的改善,而且在使用tegaserod 12毫克時對於該結果也沒有出現顯著的趨勢。在使用12毫克tegasero慢性便秘患者,以每週完全自發性排便為反應條件的RR為1.54(95% CI 1.35 to1.75),與安慰劑相比這個端點的加權平均差異0.6(95%CI 0.42 to 0.78)。 tegaserod和安慰劑之間的差異在增加排便頻率是小的(少於每週一次)。在該兩種診斷(CIBS和DIBS)患者經歷腹瀉的比例,與安慰劑組相比12毫克tegaserod顯著地較高(RR 2.80,95%CI 2.13 to 3.68),NNH為20。tegaserod對於胃腸道症狀,如腹脹,大便硬度和用力的影響在各個研究間並不一致。

作者結論

tegaserod似乎改善慢性便秘患者整體IBS的症狀,以及排便頻率。這些中度改善的臨床重要性目前尚不清楚。目前只有一些數據針對生活品質的影響。此外,需要更多信息有關其對於男性的療效。作者也有興趣知道是否tegaserod會直接或間接地改變內臟的敏感性或精神病理情形,這也被視為這些狀況在病理生理學上重要的現象。

翻譯人

本摘要由臺中榮民總醫院王建得翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

當tegaserod使用在治療便秘型腸躁症和慢性便秘可產生中度的益處。腸躁症是一種以腹痛和困擾的排變習慣為特點的慢性和復發性疾病。慢性便秘的症狀經常類似於那些便秘型的躁腸症。tegaserod 是一種刺激腸胃道平滑肌的藥物,每天4 或12毫克使用12周於便秘為主要症狀的腸躁症患者時,與安慰劑相比可以產生一些益處。使用tegaserod患者報告他們的腸躁症症狀有整體的改善,每天腸道蠕動次數的增加,沒有腸道蠕動天數的減少tegaserod是否改善腹痛,腹脹,大便硬度和用力等症狀是不清楚的。當使用於治療慢性便秘時,腸子蠕動頻次隨tegaserod增加,但是在安慰劑的增加是少的。腹瀉的現象在服用12毫克的個體發生地較頻繁。需要進一步的研究評估tegaserod對生活品質的影響。因為大多數的研究對象是女性,需要更多信息有關其對於男性的療效。

Plain language summary

Tegaserod for the treatment of irritable bowel syndrome and chronic constipation

Irritable bowel syndrome (IBS) is a chronic, relapsing condition characterized by the presence of abdominal pain and disturbed bowel habit. Symptoms of chronic constipation frequently resemble those of constipation-predominant IBS. Tegaserod (4 or 12 mg/day for 12 weeks), a drug that stimulates smooth muscle in the gastrointestinal tract, produces some benefit over placebo when used to treat IBS where constipation is a major symptom. Patients taking tegaserod reported an overall improvement in their IBS symptoms, an increase in number of bowel movements per day and a reduction in number of days without bowel movements. It is not clear if tegaserod improves symptoms such as abdominal pain, bloating, stool consistency and straining. When used to treat chronic constipation, the frequency of bowel movements increased with tegaserod, but increases over those seen with placebo were small. Diarrhea occurred more often among individuals taking high dose tegaserod (12 mg/day). Further studies are needed to assess the effect of tegaserod on quality of life. More information is needed on its effectiveness in men, as most of the studies involved women.

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