Intervention Review

Pegloticase for chronic gout

  1. Amy Anderson2,
  2. Jasvinder A Singh1,*

Editorial Group: Cochrane Musculoskeletal Group

Published Online: 17 MAR 2010

Assessed as up-to-date: 30 JUN 2009

DOI: 10.1002/14651858.CD008335.pub2


How to Cite

Anderson A, Singh JA. Pegloticase for chronic gout. Cochrane Database of Systematic Reviews 2010, Issue 3. Art. No.: CD008335. DOI: 10.1002/14651858.CD008335.pub2.

Author Information

  1. 1

    Birmingham VA Medical Center, Department of Medicine, Birmingham, USA

  2. 2

    Minneapolis VA Medical Center and University of Minnesota, Medicine, Minneapolis, MN, USA

*Jasvinder A Singh, Department of Medicine, Birmingham VA Medical Center, Faculty Office Tower 805B, 510 20th Street South, Birmingham, AL 35294, USA. jasvinder.md@gmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 17 MAR 2010

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Pegloticase is a potential new treatment option for patients with chronic gout intolerant to other urate-lowering therapies.

Objectives

To assess safety (adverse events, death) and efficacy (pain, function, frequency of flares, quality of life, uric acid level, radiographic damage) of pegloticase in various doses or as compared to placebo or other interventions for treatment of hyperuricemia in patients with chronic gout.

Search methods

We searched six databases: The Cochrane Central Register of Controlled Trials (CENTRAL), via The Cochrane Library, OVID MEDLINE, CINAHL (via EBSCOHost), OVID SPORTdiscus, EMBASE and the Science Citation Index (Web of Science).

Selection criteria

All published randomized controlled trials (RCTs) or controlled clinical trials that compared various doses of pegloticase alone or pegloticase alone or in combination with other urate-lowering or anti-inflammatory medications to placebo alone or placebo in combination with these medications, in patients with gout.

Data collection and analysis

Two review authors (AA, JS) independently extracted data from the included trials, including trial and population characteristics, primary and secondary outcomes. For dichotomous and continuous outcomes, we calculated the risk ratio and mean difference, respectively with 95% confidence interval. Major outcomes were: (a) Efficacy: frequency of gout flares and change in serum uric acid; and (b) safety: adverse events, serious adverse events, withdrawals and death. Minor/secondary outcomes were pain, patient/physician global assessment, tophus burden, health related quality of life, function and radiographic progression.

Main results

Only one open-label, phase-II RCT (n=41) met the selection criteria that compared various doses of pegloticase without comparison to placebo or another treatment. Patients were randomized to one of the four doses of pegloticase for 12 to 14 weeks - 4mg every 2 weeks, 8mg every 2 weeks, 8mg every 4 weeks and 12mg every 4 weeks. Percent responders (uric acid below 6 mg/dl 80% or more time) in the four dose groups were 56%, 88%, 52% and 62%. Percent time without hyperuricemia (uric acid below 6 mg/dl) was 78%, 92%, 76% and 76% respectively. No between dose differences were noted. Most common adverse events (10% or more patients) included nephrolithiasis, arthralgia, anemia, dyspnea, headache, muscle spasms, nausea and pyrexia. 89% reported one or more gout flares during the study. Pain, patient/physician global, function, quality of life, tophus size/regression and radiographic progression were not reported in this study.

Authors' conclusions

There are no published double-blind, placebo-controlled RCTs of pegloticase. More evidence is needed to assess risks/benefits of pegloticase in patients with chronic gout.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Pegloticase for chronic gout

This summary of a Cochrane review presents what we know from research about the effect of pegloticase on chronic gout. There was one study included in this review which looked at different doses. The review shows that:

-        it is unknown whether pegloticase can improve the pain and function of people with chronic gout.

Even though there were no differences in improvement, no matter which dose of pegloticase was taken, the uric acid was better controlled in the 8 mg every 2 week dose.  In patients who had not responded to other medications, 90% of patients had below normal levels of uric acid at this dose.   

We often do not have precise information about side effects and adverse events. This is particularly true for rare but serious side effects.  Possible side effects of pegloticase are kidney stones, joint pain and anemia.

What is gout, and what is pegloticase?

Gout is a sudden, very painful joint inflammation (arthritis) that usually affects the big toe.  Due to increase in the uric acid level in blood and then in the joints, urate crystals form on the joint and make it painful to move your toe or even to touch it.   A sudden attack of gout can sometimes be followed years later by chronic gout that affects both small and large joints of hands and feet. 

Pegloticase is meant to work by converting the urate crystals to something that will not form on the joints.  It might also enable the body to handle the urate crystals that have already built up on the joint.  Pegloticase is a new gout drug that is still under development. This means that it is currently not available because it is still being tested.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

Pegloticase 對於慢性痛風的應用

Pegloticase 對於無法使用其他降低尿酸藥物的慢性痛風患者而言,是一項可能的新選擇。

目標

對於慢性痛風病患的高尿酸血症的治療,評估pegloticase在不同劑量下,或是與安慰劑或其他療法的對照下的安全性 (副作用,死亡數) 以及效果 (疼痛,生活功能,發作頻率,生活品質,尿酸濃度,影像學上的破壞) 。

搜尋策略

我們找尋了六個資料庫:The Cochrane Central Register of Controlled Trials (CENTRAL) via The Cochrane Library, OVID MEDLINE, CINAHL (via EBSCOHost) , OVID SPORTdiscus, EMBASE 以及 Science Citation Index (Web of Science) 。

選擇標準

◆ 所有刊登的隨機對照試驗或對照性臨床試驗,包括比較單獨使用不同劑量的pegloticase、單獨使用pegloticase或合併其他降尿酸、抗發炎藥物或安慰劑一起使用、以及單獨使用安慰劑或合併上數這些藥物,在痛風的病人使用。

資料收集與分析

兩位作者各自從選取的試驗中汲取資料,包括試驗和人口結構的特徵,重要和次要的結果。從二分類和連續的結果中,我們計算出風險比例和平均差異 (兩者的95% 信賴區間) 。主要的結果: (a) 效果:發作頻率和血清尿酸濃度的改變 (b) 安全性:副作用,嚴重副作用,退出試驗和死亡的個數。次要的結果:副作用、嚴重副作用、退出試驗和死亡的個數。次要的結果:疼痛、病患/醫生的全面性評估、痛風石的量、健康相關的生活品質、生活功能和影像學上的進展。

主要結論

只有一個 (n = 41) 開放性且進入第二階段的隨機對照性試驗符合選擇標準。它比較了不同劑量的pegloticase,但並沒有將之與安慰劑或其他療法做比較。病患在12 – 14個禮拜間被隨機分配到四種劑量的群組中 (每兩週4毫克/分升,每兩週8毫克/分升,每兩週8毫克/分升,每兩週12毫克/分升) 。四個群組中有效 (尿酸濃度低於6毫克/分升在至少80% 的研究期間中) 人數比例分別為56%, 88%, 52%, 62%. 四個群組中尿酸濃度低於6毫克/分升的次數比例分別為78%, 92%, 76%, 76% 。在不同劑量兼併沒有統計上差異。最常見的副作用 (大於10% 的病患) 包括腎結石,關節痛,貧血,呼吸困難,頭痛,肌肉痙攣,噁心,和發燒。在試驗期間,89% 的病患曾有一次以上的痛風發作。疼痛,病患/醫生的全面性評估,生活功能,生活品質,痛風石大小/消減,和影像學上的變化則沒有被記錄在這個試驗中。

作者結論

目前沒有雙盲,安慰劑對照的pegloticase隨機性對照試驗被刊登。還需要更多的證據來評估其對於慢性痛風病患的優點和風險。

翻譯人

本摘要由羅東博愛醫院洪綱翻譯。

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

總結

一,pegloticase對於慢性痛風病患 這篇考科藍的回顧代表了目前我們對於pegloticase對慢性痛風病患其效果的認識。本篇只涵蓋了一篇對不同劑量的做研究的文章。它顯示對於慢性痛風病患能否改善疼痛和促進生活功能仍然未知。雖然對於不同劑量的病患來說,進步是差不多的,但是尿酸的控制在每兩週8毫克/分升這組中是比較好的:對於對其他藥物沒有反應的病患來說,90% 的病患其尿酸濃度可以達到低於正常水準。 我們通常不會有關於副作用和不良事件的確切的資訊,尤其是少見且嚴重的副作用。可能的副作用包括:腎結石,關節痛,和貧血。 二,什麼是痛風,又什麼是pegloticase? 痛風是一個突發性非常疼痛的關節發炎,同常好發於大拇趾。尿酸會因為血液中的濃度升高而在關節中產生結晶,不但移動腳指會痛,甚至碰一下都痛。有時候影響手腳的大小關節的慢性痛風,會在幾年後造成急性痛風的突然發作。Pegloticase的作用是把尿酸結晶轉化為其他不會堆積在關節上的物質。它也會幫忙對付已經堆積在關節中的尿酸結晶。Pegloticase是一個仍在開發階段的新藥,仍在測試當中,也因此它目前還買不到。