Rifabutin for treating pulmonary tuberculosis

 

Abstract

Background

Rifamycins are an essential component of modern short-course regimens for treating tuberculosis. Rifabutin has favourable pharmacokinetic and pharmacodynamic properties and is less prone to drug−drug interactions than rifampicin. It could contribute to shortening of therapy or simplify treatment in HIV-positive people who also need antiretroviral drugs.

Objectives

To compare combination drug regimens containing rifabutin with those containing rifampicin for treating pulmonary tuberculosis

Search methods

We searched Cochrane Infectious Diseases Group Specialized Register (July 2009), CENTRAL (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to July 2009), EMBASE (1974 to July 2009), and LILACS (1982 to July 2009). We also searched the Indian Journal of Tuberculosis (1983 to 2006), conference abstracts, reference lists, and unpublished data on file at Pfizer Inc.

Selection criteria

Randomized and quasi-randomized trials including participants with sputum smear and/or culture-confirmed tuberculosis that compared a rifabutin-containing with an otherwise identical rifampicin-containing regimen.

Data collection and analysis

Two authors independently assessed study eligibility and methodological quality, and extracted data. Dichotomous data were analysed and combined using relative risks (RR) with 95% confidence intervals (CI) using a fixed-effect model. Subgroup analyses were carried out according to rifabutin dose.

Main results

Five trials with a total of 924 participants met the inclusion criteria; 5% of participants were HIV positive. Only one small trial was methodologically adequate. The two largest trials (818 participants) had unclear allocation concealment and included < 90% of randomized participants in the analysis. There was no statistically significant difference in between the regimens for cure (RR 1.00, 95% CI 0.96 to 1.04; 553 participants, 2 trials) or relapse (RR 1.23, 95% CI 0.45 to 3.35; 448 participants, 2 trials). The number of adverse events was not significantly different (RR 1.42, 95% CI 0.88 to 2.31; 714 participants, 3 trials), though the RR increased with rifabutin dose: 150 mg (RR 0.98, 95% CI 0.45 to 2.12; 264 participants, 2 trials); and 300 mg (RR 1.78, 95% CI 0.94 to 3.34; 450 participants, 2 trials). However, lack of dose adjustment by weight in the relevant trials complicates interpretation of this relationship.

Authors' conclusions

The replacement of rifampicin by rifabutin for first-line treatment of tuberculosis is not supported by the current evidence. HIV-positive people with tuberculosis, the group most likely to benefit from the rifabutin use, are under-represented in trials to date, and further trials in this group would be useful.

 

Plain language summary

Rifabutin for treating pulmonary tuberculosis

Among current challenges in tuberculosis treatment are reducing the length of time that drugs must be taken to less than six months and finding ways to safely combine tuberculosis drugs with those used in the treatment of HIV infection. Rifabutin is a drug that has the potential to address these issues if substituted for rifampicin, a mainstay of current treatment. This review identified five trials involving 924 people, but none were of high quality. The review found no significant differences between rifabutin- and rifampicin-containing treatment in curing tuberculosis and preventing relapse, but higher doses of rifabutin might be associated with more adverse effects and there was no evidence that it could shorten treatment. However, very few people with HIV and tuberculosis, who are most likely to benefit from use of rifabutin due to its lack of interaction with antiretroviral drugs, were included in the trials. Better quality clinical trials are needed to understand the place of rifabutin in the treatment of people with tuberculosis, particularly those who also have HIV.

 

摘要

背景

Rifabutin於肺結核治療評估

Rifamycins為目前短療程肺結核治療藥物之主要藥物，Rifabutin極佳藥物動力學與藥效學特性，相較於Rifamycins藥物，Rifabutin不易與&−藥物發生交互作用。Rifamycins應用價值在於可縮短療程或是對於HIV(+)且同時需服用antiretroviral藥物之病患,進行簡單治療。

目標

本研究目的主要討論藥物合併rifabutinri或fampicin對於肺結核治療效果。

搜尋策略

我們搜尋Cochrane Infectious Diseases Group Specialized Register(January 2007)、CENTRAL(The Cochrane Library 2006, Issue 4)、MEDLINE(1966 to January 2007)、EMBASE(1974 to January 2007)與LILACS(1982 to January 2007)等資料庫。同時也搜尋Indian Journal of Tuberculosis(1983 to 2006)、會議摘要論文、列出之參考文獻，及輝瑞藥廠中尚未發表之資料。

選擇標準

以隨機方式及半隨機方式進行臨床試驗，以痰抹片或經培養證實為結核患者作為臨床試驗對象的選擇，主要評估藥物合併rifabutinri或fampicin對於肺結核治療效果。

資料收集與分析

兩位作者個別獨自進行研究方法的品質評估與合格數據審定。對於二元變項數據(dichotomous data)，合併採用相對風險(relative risks;RR)之95%信賴區間(95% confidence intervals;CI)與固定效果模式(fixedeffect model)來評估。次群分析則依據rifabutin劑量計算。

主要結論

總共進行5個臨床試驗，924位受試者符合試驗篩選標準，其中，5%受試者為HIV陽性。只有一個小試驗的究方法是適當的.有2個最大的臨床試驗(818位受試者)其分配隱藏不清楚及隨機受試者小於90%。數據顯示，無論是以痊癒(RR值1.00,95%信賴區間0.96 – 1.04，553位受試者，2個臨床試驗)或復發(RR值1.23，95%信賴區間0.45 – 3.35，448位受試者，2個臨床試驗)來評估，兩種藥物均無統計學上顯著差異。總共進行5個臨床試驗，924位受試者符合試驗篩選標準，其中5%受試者為HIV(+)。只有一小部分研究方法品質是適當的。有2個臨床試驗(818位受試者)有不清楚的分配隱藏及小於90%隨機受試者族群。數據顯示，無論是以痊癒(RR值1.00，95%信賴區間0.96 – 1.04，553位受試者，22個臨床試驗)或復發(RR值1.23，95%信賴區間0.45 – 3.35，448位受試者，2個臨床試驗)來評估，兩種藥物均無統計學上顯著差異.不良反應件數來說，兩者無顯著差異(RR值1.42，95%信賴區間0.88 – 2.31，714位受試者，3個臨床試驗)，雖然當rifabutin劑量高達150 mg，RR值上升(RR值0.98，95%信賴區間0.45 – 2.12，264位受試者，2個臨床試驗)，高達300 mg時，RR值上升(RR值1.78，95%信賴區間0.94 – 3.34，450位受試者，2個臨床試驗)。不過，在本試驗中缺乏將權重因子納入適當的劑量評估內，使得彼此關聯性評估變的複雜。

作者結論

由目前證據並無法支持Rifabutin可以取代rifampicin作為第一線治療藥物。試驗至今，rifabutin對於少數同時感染肺結核與HIV患者來說，似乎是有益處的，本結果對未來臨床試驗相當有幫助。

翻譯人

本摘要由三軍總醫院樊修龍翻譯。

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

總結

Rifabutin應用在肺結核治療，目前最大的挑戰是降低少於6個月的服藥期，以及尋求一個安全的方法，可同時進行HIV感染治療。 Rifabutin是一種具潛力以取代rifampicin之治療藥物。本研究包括924人次之5項臨床試驗，但沒有一項是高品質的。由研究結果得知，比較服用含rifabutin或rifampicin藥物，對於肺結核治療與預防復發效果，兩者並無顯著差異。投與較高劑量rifabutin可能造成較多不良作用外，且無任何證據顯示可縮短療程。而因rifabutin與antiretroviral drugs不太發生藥物交互作用，而使得rifabutin在對於臨床試驗中少數同時感染肺結核與HIV患者來說，是有益處的。期望有更好的臨床試驗設計，能進一步了解以rifabutin藥物對肺結核感染治療效果，特別是同時感染HIV之患者。