Darbepoetin for the anaemia of chronic kidney disease

  • Review
  • Intervention

Authors

  • Suetonia C Palmer,

    1. University of Otago Christchurch, Department of Medicine, Christchurch, New Zealand
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  • Valeria Saglimbene,

    1. Mario Negri Sud Consortium, Clinical Pharmacology and Epidemiology, Santa Maria Imbaro, Chieti, Italy
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  • Jonathan C Craig,

    1. The University of Sydney, Sydney School of Public Health, Sydney, NSW, Australia
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  • Sankar D Navaneethan,

    1. Glickman Urological and Kidney Institute, Cleveland Clinic, Department of Nephrology and Hypertension, Cleveland, OH, USA
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  • Giovanni FM Strippoli

    Corresponding author
    1. The University of Sydney, Sydney School of Public Health, Sydney, NSW, Australia
    2. The Children's Hospital at Westmead, Cochrane Renal Group, Centre for Kidney Research, Westmead, NSW, Australia
    3. University of Bari, Department of Emergency and Organ Transplantation, Bari, Italy
    4. Mario Negri Sud Consortium, Department of Clinical Pharmacology and Epidemiology, Santa Maria Imbaro, Italy
    5. Diaverum, Medical-Scientific Office, Lund, Sweden
    6. Amedeo Avogadro University of Eastern Piedmont, Division of Nephrology and Transplantation, Department of Translational Medicine, Novara, Italy
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Abstract

Background

Erythropoiesis-stimulating agents are used to treat anaemia in people with chronic kidney disease (CKD). Several agents are available including epoetin alfa or beta as well as agents with a longer duration of action, darbepoetin alfa and methoxy polyethylene glycol-epoetin beta.

Objectives

To assess the benefits and harms of darbepoetin alfa to treat anaemia in adults and children with CKD (stages 3 to 5, 5D, and kidney transplant recipients).

Search methods

We searched the Cochrane Renal Group's Specialised Register (to 13 January 2014) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE.

Selection criteria

We included randomised controlled trials of any darbepoetin alfa treatment of at least three months duration in adults or children with CKD (any stage).

Data collection and analysis

Data were extracted by two independent investigators. Patient-centred outcomes (need for blood transfusion, iron therapy, progression of kidney disease, total and cardiovascular mortality, cardiovascular events, cancer, hypertension, seizures, and health-related quality of life) and other outcomes (haemoglobin levels) were assessed using random effects meta-analysis. We calculated risk ratios for dichotomous outcomes and mean differences for continuous outcomes, both with 95% confidence intervals.

Main results

We identified 32 studies comprising 9414 participants; 21 studies in 8328 participants could be included in our meta-analyses. One study (4038 participants) compared darbepoetin alfa to placebo, 16 studies (2955 participants) compared darbepoetin alfa to epoetin alfa or beta, four studies (1198 participants) compared darbepoetin alfa to methoxy polyethylene glycol-epoetin beta, three studies (420 participants) compared more frequent with less frequent darbepoetin alfa administration and four studies (303 participants) compared intravenous with subcutaneous darbepoetin alfa administration.

In a single large study, darbepoetin alfa reduced the need for blood transfusion and iron therapy compared with placebo in adults with CKD stage 3 to 5, but had little or no effect on survival, increased risks of hypertension, and had uncertain effects on quality of life. Data comparing darbepoetin alfa with epoetin alfa or beta or methoxy polyethylene glycol-epoetin beta were sparse and inconclusive. Comparisons of differing dosing schedules and routes of administration were compared in small numbers of participants and studies. Evidence for treatment effects of darbepoetin alfa were particularly limited for children with CKD, adults with CKD stage 5D, and recipients of a kidney transplant.

Studies included in this review were generally at high or unclear risk of bias for all items (random sequence generation, allocation concealment, incomplete outcome data, blinding of participants and personnel, blinding of outcome assessment, selective outcome reporting, intention to treat analysis and other sources of bias). One large study comparing darbepoetin alfa with placebo was at low risk of bias for most items assessed.

Authors' conclusions

Data suggest that darbepoetin alfa effectively reduces need for blood transfusions in adults with CKD stage 3 to 5, but has little or no effect on mortality or quality of life. The effects of darbepoetin alfa in adults with CKD stage 5D and kidney transplant recipients and children with CKD remain uncertain as do the relative benefits and harms of darbepoetin alfa compared with other ESAs (epoetin alfa or beta and methoxy polyethylene glycol-epoetin beta).

摘要

以Darbepoetin治療慢性腎臟疾病的貧血症

背景

使用紅血球生成刺激劑 (erythropoiesis-stimulating agent) 治療慢性腎臟疾病 (chronic kidney disease, CKD) 患者的貧血。目前有幾種市售產品可供利用,包括epoetin alfa、epoetin beta,以及作用時間較長的darbepoetin alfa和methoxy polyethylene glycol-epoetin beta。

目的

評估以darbepoetin alfa治療CKD (第3至5期、5D和接受腎臟移植患者) 成人及兒童患者的利弊得失。

搜尋策略

我們聯絡試驗搜尋協調員,利用與本次文獻回顧相關的字彙,搜尋考科藍腎臟群組專業註冊 (Cochrane Renal Group's Specialised Register) (截至2014年1月13日為止)。透過專為CENTRAL、 MEDLINE和EMBASE設計的搜尋策略,找出專業註冊所收錄的試驗。

選擇標準

我們收錄隨機對照試驗,以任何darbepoetin alfa治療成人或兒童CKD患者 (任何期數),且治療時間持續至少3個月。

資料收集與分析

由2位獨立的試驗主持人進行資料萃取。採用隨機效果後設分析 (random effects meta-analysis),評估以患者為中心的結果 (輸血需求、鐵劑治療、腎臟疾病的進展、總死亡率與心血管死亡率、心血管事件、癌症、高血壓、癲癇和健康相關生活品質 [health-related quality of life]) 以及其他結果 (血紅素濃度)。我們計算二元性結果資料的風險比 (risk ratio) 和連續性結果的平均差 (mean difference),並報告兩者的 95% 信賴區間 (confidence interval)。

主要結果

本次文獻回顧找到32篇試驗,包含9414名受試者,並將其中21篇試驗 (包含8328名受試者) 納入後設分析。其中有1篇試驗 (4038名受試者) 比較darbepoetin alfa與安慰劑;有16篇試驗 (2955名受試者) 比較darbepoetin alfa與epoetin alfa或epoetin beta;有4篇試驗 (1198名受試者) 比較darbepoetin alfa與methoxy polyethylene glycol-epoetin beta;有3篇試驗 (420名受試者) 比較darbepoetin alfa的使用頻率 (高、低);有4篇試驗 (303名受試者) 比較靜脈注射與皮下注射darbepoetin alfa。

有一篇大型試驗指出,相對於安慰劑,darbepoetin alfa可降低第3至5期CKD成人患者的輸血與鐵劑治療需求,但對存活期的影響很小或毫無影響;會使高血壓風險增加,但對生活品質的影響不明。darbepoetin alfa與epoetin alfa、epoetin beta或methoxy polyethylene glycol-epoetin beta的比較資料很少,而且結果亦不明確定。比較各種劑量與給藥途徑的試驗,不但數量很少,而且收錄的受試者人數也不多。關於darbepoetin alfa對CKD兒童患者、5D期CKD成人患者,以及接受腎臟移植患者的療效證據尤其有限。

本次文獻回顧所納入的試驗,所有項目的偏差風險 (產生隨機序列的方式、分組隱匿 [allocation concealment]、不完整的研究結果報告、受試者和試驗人員的盲性、結果評估的盲性、選擇性結果報告、治療意向分析 [intention to treat analysis],以及其他來源的偏差) 通常偏高或不明。有1項比較darbepoetin alfa與安慰劑的大型試驗,大部分評估項目的偏差風險偏低。

作者結論

資料顯示,darbepoetin alfa可降低第3至5期CKD成人患者的輸血需求,但對存活期或生活品質的影響很小或毫無影響。至於比較darbepoetin alfa和其他紅血球生成刺激劑 (ESA) (epoetin alfa、epoetin beta和 methoxy polyethylene glycol-epoetin beta) 的相對效益和傷害試驗則顯示,darbepoetin alfa對第5D期CKD成人患者、接受腎臟移植成人患者和CKD兒童患者的療效尚不明確。

譯註

翻譯者:臺北醫學大學實證醫學研究中心。本翻譯計畫由衛生福利部補助經費,臺北醫學大學實證醫學研究中心、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行。

Plain language summary

Darbepoetin alfa to treat anaemia in people with chronic kidney disease

People who have chronic kidney disease (CKD) frequently experience anaemia. Several different medicines that treat anaemia are available including darbepoetin alfa.

We investigated whether darbepoetin alfa might have different effects in people with CKD compared to placebo or no treatment, or similar other treatment options called epoetin or methoxy polyethylene glycol-epoetin beta, and whether differing ways of administering darbepoetin (route and frequency of treatment) might have different benefits and harms for people who have CKD.

While darbepoetin alfa reduced the need for patients to have blood transfusions to treat severe anaemia, darbepoetin alfa had little or no effect on survival or chances of needing dialysis therapy and their overall quality of life.

There were not enough studies comparing darbepoetin alfa with other similar treatment options to provide sufficient information to guide clinical decision-making about choosing which medicine is best for an individual patient.

Little information was available about darbepoetin treatment for children who have CKD and adults who have received a kidney transplant or those treated with dialysis.

淺顯易懂的口語結論

以Darbepoetin alfa治療慢性腎臟疾病患者的貧血症

慢性腎臟疾病的患者經常發生貧血,目前已有數種不同的藥物可用來治療貧血,包括darbepoetin alfa在內。

我們希望相對於安慰劑、無治療介入,類似的其他治療選擇 (即 epoetin 或 methoxy polyethylene glycol-epoetin beta),探究darbepoetin alfa對CKD患者是否具有不同的療效;並且研究不同的darbepoetin用法 (治療途徑和頻率),對CKD患者是否具有不同的療效和傷害。

雖然darbepoetin alfa可降低患者因嚴重貧血而必須輸血治療的需求,但darbepoetin alfa對患者的存活期、需要透析治療的機率以及整體生活品質,影響卻很小或毫無影響。

關於darbepoetin alfa和其他類似治療選擇的比較試驗數量不足,無法提供充分的資訊,引導醫師針對個別患者的狀況進行臨床決策,選擇最適當的藥物治療。

關於 CKD兒童患者、接受腎臟移植成人患者,以及接受透析治療患者的darbepoetin治療資訊相當有限。

譯註

翻譯者:臺北醫學大學實證醫學研究中心。本翻譯計畫由衛生福利部補助經費,臺北醫學大學實證醫學研究中心、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行。

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