Drugs for discoid lupus erythematosus

 

Abstract

Background

Discoid lupus erythematosus is a chronic form of cutaneous (skin) lupus which can cause permanent scarring if treatment is inadequate. Many drugs have been used to treat this disease and some of these are potentially very toxic.

Objectives

To assess the effects of drugs for discoid lupus erythematosus.

Search methods

In June 2009 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2009), MEDLINE, EMBASE, LILACS, and online ongoing trials registers. The reference lists of relevant reviews were searched. Index Medicus (1956 to 1966) was handsearched and we approached authors for information about unpublished trials.

Selection criteria

We included all randomised trials of drugs to treat people with discoid lupus erythematosus. Drugs included in the search were azathioprine, chloroquine, clofazimine, corticosteroids, (oral and topical), dapsone, gold, interferon alpha-2a, methotrexate, phenytoin, retinoids, sulphasalazine, thalidomide, topical calcineurin blockers (pimecrolimus and tacrolimus), and biological agents (etanercept, efalizimab, infliximab, and rituximab).

Data collection and analysis

Two reviewers independently examined each retrieved study for eligibility.

Main results

Two trials involving 136 participants were included. No new trials were included in this update.

In a cross-over study of 12 weeks duration, fluocinonide 0.05% cream (a potent topical corticosteroid), appeared to be better than hydrocortisone 1% cream (a mild corticosteroid) when the first arm of the trial involving 78 participants was analysed at 6 weeks. Clearing or excellent improvement was seen in 27% of people using fluocinonide and in 10% of those using hydrocortisone, giving a 17% absolute benefit in favour of fluocinonide (95% CI 0.0 to 0.34, NNT (Number needed to treat) 6).

In the second trial, acitretin (50mg/day) was compared with hydroxychloroquine (400mg/day) in 58 people in a parallel trial of 8 weeks duration. There was marked improvement or clearing in 46% of people using acitretin and in 50% of those on hydroxychloroquine but there was no significant difference between the 2 interventions. The adverse effects were more frequent and more severe in the acitretin group. In this trial clearing of erythema was measured and found to be better in the hydroxychloroquine group (RR 0.61, 95% CI 0.36 to 1.06).

Authors' conclusions

Fluocinonide cream may be more effective than hydrocortisone in treating people with discoid lupus erythematosus. Hydroxychloroquine and acitretin appear to be of equal efficacy, although adverse effects are more frequent and more severe with acitretin. There is not enough reliable evidence about other drugs used to treat discoid lupus erythematosus.

 

Plain language summary

Drugs for discoid lupus erythematosus

Discoid lupus erythematosus (DLE) is a severe form of skin inflammation which occurs particularly on sun-exposed skin. It can cause permanent scarring but this can be prevented by early treatment. All forms of cutaneous lupus erythematosus are most common in women of childbearing age: this is particularly important because some treatments, including thalidomide and retinoids, cause birth defects. This review found that fluocinonide cream is more effective than hydrocortisone. Hydroxychloroquine and acitretin appear to work equally well, although acitretin has more frequent and severe adverse effects. Participants taking acitretin showed a small increase in serum triglyceride, not sufficient to require withdrawal of the drug. The acitretin trial was flawed by the inclusion of people with subacute cutaneous lupus and by the lack of a placebo arm. The trial does not provide evidence that either hydroxychloroquine or acitretin will be effective in people not responding to the other agent as it did not use a cross-over design.

 

摘要

背景

盤狀紅斑性狼瘡的藥物治療

盤狀紅斑性狼瘡是一種慢性的皮膚紅斑性狼瘡，若無適當治療，可導致永久性的疤痕。許多藥物都被用來治療這個疾病，其中有些藥物潛在地具有相當大的毒性。

目標

評估盤狀紅斑性狼瘡各種藥物的治療效果。

搜尋策略

2009年6月，我們更新了搜尋，包括the Cochrane Skin Group Specialised Register，the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2009年第二期), MEDLINE, EMBASE LILACS, 以及網路上註冊進行中的臨床試驗。也搜尋了相關回顧性文獻的參考書目。我們也翻閱了Index Medicus (1956到1966) ，並且諮詢了未出版臨床試驗的作者意見。

選擇標準

針對盤狀紅斑性狼瘡藥物治療的隨機臨床試驗。包含的藥物有：azathioprine, chloroquine, clofazimine, corticosteroids (口服及外用), dapsone, gold, interferon alpha2a, methotrexate, phenytoin, retinoids, sulphasalazine, thalidomide, 外用calcineurin blockers (pimecrolimus 及 tacrolimus), 以及生物製劑 (etanercept, efalizimab, infliximab, 及rituximab) 。

資料收集與分析

2位獨立作業的審查員檢視各檢索研究的資格。

主要結論

本文總共收錄2件臨床試驗，共包含136位病人。在此更新版中並沒有加入新的臨床試驗。第一個為其12週的橫斷性研究中，在第6週時分析本試驗第一組的78位受試者，發現使用fluocinonide 0.05% cream (強效的外用類固醇) 明顯地比使用hydrocortisone 1% cream (溫和的外用類固醇) 來得有效。在fluocinonide組裡，病灶的清除或明顯地進步共占27% ，而在hydrocortisone組，只有10% 。因此fluocinonide有17% 的絕對好處 (95% CI 4.5到29.5% ，NNT6 (Number needed to treat需要治療數目) 6)) 。在第二個為期8週的平行臨床試驗 (parallel trial) 中，比較了58位病人使用hydroxychloroquine (50mg/day) 與acitretin (400mg/day) 的效果。使用acitretin病人有46% 達到明顯改善或病灶消失，而hydrochloroquine則是50% 。副作用方面，acitretin組的發生率和嚴重度均較高。本試驗裡，清除紅斑的效果在hydroxychloroquine組較好 (RR 0.61, 95% CI 0.36到1.06) 。

作者結論

對盤狀紅斑性狼瘡的治療，Fluocinonide可能比hydrocortisone更有效。 Hydroxychloroquine與acitretin的療效似乎差異不大，但acitretin的副作用較常見，且較嚴重。在其他治療盤狀紅斑性狼瘡的其他藥物，目前並沒有足夠可靠的研究證據。

翻譯人

本摘要由馬偕醫院王仁佑翻譯。

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

總結

盤狀紅斑性狼瘡的藥物治療。 盤狀紅斑性狼瘡 (discoid lupus erythematosus, DLE) 是一種嚴重的皮膚發炎性疾患，好發在日照部位；也可造成永久性的疤痕，但早期治療可以避免疤痕產生。各種形式的DLE都是最常發生於孕齡婦女，這對於某些治療方式非常重要。因為有些治療，包括thalidomide及retinoids，可造成嬰兒的缺陷。本篇回顧性研究發現，fluocinoinide乳霜比hydrocortisone有效。而hydroxychloroquine與acitretin效力相當，不過acitretin較常有較嚴重的副作用。使用acitretin的病人會出現血清三酸甘油脂的小幅上升，但尚未需要因此停藥。此acitretin臨床試驗的缺陷是同時納入了亞急性皮膚紅斑性狼瘡的病人，而且缺乏一個安慰劑組。此臨床試驗並未使用交叉治療的設計，所以無法對使用hydroxychloroquine或acitretin無效的病人，換用另一藥物是否有效提供證據。