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Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia

  • Review
  • Intervention

Authors


Abstract

Background

Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red blood cells.

Repeated transfusions results in excessive accumulation of iron in the body (iron overload), removal of which is achieved through iron chelation therapy. Desferrioxamine is the most widely used iron chelator. Substantial data have shown the beneficial effects of desferrioxamine. However, important questions exist about whether desferrioxamine is the best schedule for iron chelation therapy.

Objectives

To determine the effectiveness (dose and method of administration) of desferrioxamine in people with transfusion-dependent thalassaemia.

Search methods

We searched the Cochrane Haemoglobinopathies Trials Register, MEDLINE, EMBASE, ZETOC, Current Controlled Trials and bibliographies of relevant publications. We also contacted the manufacturers of desferrioxamine and other iron chelators.

Date of last searches: April 2004.

Selection criteria

Randomised controlled trials comparing desferrioxamine with placebo; with another iron chelator; or comparing two schedules of desferrioxamine, in people with transfusion-dependent thalassaemia.

Data collection and analysis

Four authors working independently, were involved in trial quality assessment and data extraction. Missing data were requested from the original investigators.

Main results

Eight trials involving 334 people (range 20 to 144 people) were included. One trial compared desferrioxamine with placebo, five compared desferrioxamine with another iron chelator (deferiprone) and two compared different schedules of desferrioxamine. Overall, few trials measured the same outcomes.

Compared to placebo, desferrioxamine significantly reduced iron overload. The number of deaths at 12 years follow up and evidence of reduced end-organ damage was less for desferrioxamine than placebo. When desferrioxamine was compared to deferiprone or a different desferrioxamine schedule there were no statistically significant differences in measures of iron overload. Compliance was recorded by two trials. Compliance was less for desferrioxamine than deferiprone in one trial and of no difference in comparison with desferrioxamine and deferiprone combined with a second trial.

Adverse events were recorded in trials comparing desferrioxamine with other iron chelators. There was evidence of adverse events in all treatment groups. In one trial, adverse events were significantly less likely with desferrioxamine than deferiprone, relative risk 0.45 (95% confidence interval 0.24 to 0.84).

Assessment of the methodological quality of included trials was not possible, given the general absence of these data in the trials.

Authors' conclusions

We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

摘要

背景

利用desferrioxamine mesylate來治療輸血依賴型海洋性貧血患者的鐵負荷過多

重度海洋性貧血(thalassemia major)是一種血紅素製造能力下降的遺傳性疾病;其所造成的貧血,要透過紅血球輸血來處理。反覆輸血會造成鐵質在身體裡過度堆積(鐵負荷過多),得藉由鐵螯合治療(iron chelation therapy)才能把這些鐵給排除。Desferrioxamine是最廣泛使用的鐵螯合劑(iron chelator; 俗稱「排鐵劑」),已有大量資料顯示其益處。然而,desferrioxamine是否為最好的鐵螯合治療方針仍有疑問。

目標

探討desferrioxamine用於輸血依賴型海洋性貧血的療效(劑量與給藥方式)。

搜尋策略

我們搜尋了Cochrane Haemoglobinopathies Trials Register、MEDLINE、EMBASE、ZETOC、Current Controlled Trials等資料庫以及相關文獻的參考書目。我們也與desferrioxamine及其他鐵螯合劑的製造商連絡。最後搜尋時間:2004年4月。

選擇標準

針對輸血依賴型海洋性貧血患者,比較desferrioxamine與安慰劑;與其他鐵螯合劑;或兩種不同的desferrioxamine給藥時程的隨機對照試驗(randomised controlled trials)。

資料收集與分析

由4位作者獨立工作,評估試驗品質並選取資料。資料有缺,則向原研究者索取。

主要結論

本文共引入了包含334位病人(範圍從20到144人)的8個試驗。有1個試驗比較desferrioxamine與安慰劑,5個比較desferrioxamine與另一種鐵螯合劑(deferiprone),而2個比較不同的desferrioxamine給藥時程。整體而言,只有少數試驗測量相同的預後因子。與安慰劑相比,desferrioxamine顯著降低鐵負荷,且在12年後追蹤的死亡人數和終端器官損傷(endorgan damage)的情況皆比安慰劑少。當desferrioxamine與deferiprone或不同的desferrioxamine給藥時程相比,在鐵負荷過多的測量方面並沒有顯著統計差異。有2個試驗有紀錄給藥順從性(compliance);其中1個顯示desferrioxamine的給藥順從性比deferiprone差,另1個則發現desferrioxamine和desferrioxamine與deferiprone合併使用的給藥順從性沒有差異。在比較desferrioxamine和其他鐵螯合劑的試驗中,有紀錄到不良事件(adverse events)。實際上所有治療組都有不良事件。在1個試驗中,desferrioxamine的不良事件發生率顯著低於deferiprone (RR 0.45, 95% CI 0.24 to 0.84)。由於相關資料廣泛地不足,本文所引入試驗的方法學品質(methodological quality)無法評估。

作者結論

我們找不到改變現有治療建議的理由。然而,在輸血依賴型海洋性貧血患者中,孰為適當的desferrioxamine給藥時程仍存有一定的不確定性。

翻譯人

本摘要由臺灣大學附設醫院劉彥麟翻譯。

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

總結

隨機對照試驗尚無充分數據證明鐵螯合劑desferrioxamine用於輸血依賴型海洋性貧血患者的療效 海洋性貧血是一種血紅素製造能力下降的遺傳性疾病。規則輸血治療會導致身體中的鐵過多,而移除這些過多的鐵對於預防重要器官損傷非常重要。鐵螯合治療可將過剩的鐵移除,其中用得最廣的是desferrioxamine。本回顧發現利用desferrioxamine進行鐵螯合治療雖對某些人有副作用,但與沒有鐵螯合治療相比仍具療效。然而,孰為適當的desferrioxamine給藥時程仍存有一定的不確定性。

Plain language summary

Desferrioxamine mesylate for managing excess iron levels in the blood in people with thalassaemia who depend on blood transfusions

Thalassaemia is a genetic disease. People with thalassaemia are not able to produce enough haemoglobin. Haemoglobin is the part of the blood which carries oxygen around the body. A lack of this leads to anaemia. Treatment with blood transfusions leads to high levels of iron in the body. Excess iron must be removed to prevent damage to major organs. This is done through iron chelation therapy: the most widely used drug is desferrioxamine. The review includes eight trials which compared desferrioxamine to placebo or another iron chelator or to different doses of desferrioxamine. The review found that desferrioxamine is better than no iron chelation. But the drug does have side effects in some people. One trial showed fewer adverse events with desferrioxamine than another iron chelator. The best dosage of desferrioxamine is still very uncertain. Further research should answer this question. We can not recommend any change in practice at this time.

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