Hydroxyurea for sickle cell disease

 

Abstract

Background

Sickle cell disease is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea, an oral chemotherapeutic drug, is expected to ameliorate some of the clinical problems of sickle cell disease, in particular that of pain, by raising fetal haemoglobin.

Objectives

To assess the effects of hydroxyurea therapy in people with sickle cell disease (all types), of any age, regardless of setting.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.

Date of the most recent search: 12 May 2010.

Selection criteria

All randomised or quasi-randomised controlled trials comparing the use of hydroxyurea for one month or longer with placebo, standard therapy or other interventions for the treatment of people with sickle cell disease.

Data collection and analysis

Three authors independently assessed study quality and extracted data from the two included studies.

Main results

Two studies found by the searches, which reported results from a total of 324 adults and children, were suitable for inclusion in the review. From the data provided in the published reports, only one study (the MSH study to the United States of America) could be analysed. This study showed marked differences in favour of hydroxyurea treatment as compared with placebo in terms of annual crisis rate, use of transfusions, and life-threatening complications (in particular, acute sickle chest syndrome). Both studies documented the expected rise in fetal haemoglobin. No serious adverse effects were reported from either study.

Authors' conclusions

While hydroxyurea appears both effective and safe in severely affected SS adults over a two-year period; further studies are required to elucidate its role in other patient groups and for other conditions.

 

Plain language summary

Hydroxyurea for people with sickle cell disease

Haemoglobin is the substance within the red blood cells that carries oxygen around the body. Sickle cell disease (SCD) is an inherited genetic disorder where there are problems with the haemoglobin. Crystals form in the red blood cells and block the blood flow. This causes pain and organ damage. Fetal haemoglobin stops crystals forming in the sickle haemoglobin within the red blood cell. So, raising the fetal haemoglobin level in people with SCD can reduce the effects of the disease. The drug hydroxyurea is used to raise fetal haemoglobin. We looked for studies which compared hydroxyurea to placebo for longer than one month. The review includes two studies with 324 people. One study is waiting to be assessed. We were only able to analyse data from one study which lasted two years. This study favoured hydroxyurea compared with placebo for the outcomes: annual crisis rate; use of transfusions; and life-threatening complications. Both studies described the expected rise in fetal haemoglobin. No serious adverse effects were reported from either study. We conclude that hydroxyurea can raise fetal haemoglobin levels in adults with SCD without any adverse effects.

 

摘要

背景

Hydroxyurea用於鐮刀型貧血症(sickle cell disease)

鐮刀型貧血症(sickle cell disease)是世界上最常見的遺傳疾病之一，它會減少患者的壽命並且終生患病。Hydroxyurea是一種口服化學治療藥物，有人預期藉由它增加胎兒血紅素(fetal haemoglobin)的效果可以改善鎌刀型貧血症的臨床症狀，特別是在疼痛方面。

目標

評估在各類型、各年齡的鐮刀型貧血症患者使用Hydroxyurea治療的效果。

搜尋策略

我們搜尋了Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Register，其中包含電子資料庫、期刊、研討會的摘要手冊。最新的搜尋結果是：2006年11月。

選擇標準

所有隨機對照(randomised controlled)或半隨機對照試驗(quasirandomised controlled trial)，比較使用Hydroxyurea與安慰劑、標準療法或其他療法，對於鐮刀型貧血症患者的效果。

資料收集與分析

3個作者各自獨立從2篇收納的研究中擷取數據與分析研究品質。

主要結論

我們搜尋到2篇研究，合計有324個成人與小孩符合本篇回顧的收納標準。從已發表的研究數據來看，只有1篇研究可以拿來分析(美國的MSH study)。這篇研究顯示不管在每年鐮刀型貧血症引起的血管阻塞危機(Sickle cell crisis)、輸血次數和危及生命的併發症(特別是急性胸腔症候群，使用Hydroxyurea治療者明顯比安慰劑好很多。除此之外，兩篇研究都觀察到胎兒血紅素的增加，也都沒有發現任何嚴重的副作用。

作者結論

雖然Hydroxyurea對嚴重SS型鐮刀型貧血症成人患者在2年內可說是相當安全而且有效，使用在其他患者身上還需要進一步研究來闡明它的效果。

翻譯人

本摘要由臺灣大學附設醫院陳敬軒翻譯。

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

總結

對於許多鐮刀型貧血症患者，Hydroxyurea可以增加胎兒血紅素的量。血紅素是紅血球裡面負責攜帶氧氣到全身的物質。鐮刀型貧血症是一種血紅素生成異常的遺傳疾病。紅血球內會形成晶體，阻塞血流造成疼痛與器官損害。胎兒血紅素的增加干擾了紅血球內晶體的形成，進而減少疾病帶來的影響。由這篇回顧可知：Hydroxyurea是治療鐮刀型貧血症有效又沒有副作用的藥物。