Interventions for pemphigus vulgaris and pemphigus foliaceus

 

Abstract

Background

A range of interventions have been described for treatment of pemphigus, however the optimal therapeutic strategy has not been established.

Objectives

To assess the efficacy and safety of all interventions used in the management of pemphigus vulgaris and pemphigus foliaceus.

Search methods

We searched the Cochrane Skin Group Specialised Register (October 2008), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2008), MEDLINE (2003 to October 2008), EMBASE (2005 to October 2008), LILACS (1981 to October 2008), Ongoing Trials Registers, reference lists of articles, conference proceedings from international pemphigus meetings and contacted experts in the field.

Selection criteria

Randomised controlled trials of any intervention in pemphigus vulgaris or pemphigus foliaceus.

Data collection and analysis

Two authors independently assessed quality and extracted data from studies. All investigators were contacted for further information. Adverse events were identified from included studies.

Main results

Eleven studies with a total of 404 participants (337 pemphigus vulgaris, 27 pemphigus foliaceus and 40 not specified ) were identified. The quality of included studies was not high, the majority of studies did not report allocation concealment, and power was limited by very small sample sizes. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor and traditional Chinese medicine. Ten studies included participants with newly diagnosed or newly active recurrent disease, and one trial included participants in maintenance phase.

There was sufficient data for 4 meta-analyses, each pooling results of two studies only. For the majority of interventions, results were inconclusive. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall. Mycophenolate was more effective in achieving disease control than azathioprine (1 study; n=40; RR 0.72; 95% CI 0.52 to 0.99, NNT 3.7). There was evidence of a steroid-sparing benefit of azathioprine (1 study; n=57; MWD -3919 mg prednisolone; 95% CI -6712 to -1126) and cyclophosphamide (1 study; n=54; MWD -3355 mg prednisolone; 95% CI -6144 to -566) compared to glucocorticoids alone. Topical epidermal growth factor decreased time to control (1 study; n=20; HR 2.35; 95% CI 1.62 to 3.41).

Authors' conclusions

There is inadequate information available at present to ascertain the optimal therapy for pemphigus vulgaris or pemphigus foliaceus. Further research is required, especially to assess the optimal glucocorticoid dose, the role of adjuvant immunosuppressive medications, and long-term adverse events to improve harm:benefit analyses.

 

Plain language summary

Interventions for pemphigus vulgaris and pemphigus foliaceus

This review of clinical trials aimed to find out which is the most effective and safest treatment option for pemphigus vulgaris and pemphigus foliaceus.

Pemphigus vulgaris and pemphigus foliaceus are rare diseases characterised by fragile blisters and sores on the skin and mucosa. They are auto-immune diseases which are caused by the body making an antibody against the person's own skin. These diseases are chronic and are not currently curable. Pemphigus vulgaris and foliaceus are managed with drugs which suppress the immune system. The aim of treatment is to suppress blister formation. Systemic glucocorticoids are the cornerstone of management in pemphigus, however adjuvant immunosuppressive and anti-inflammatory agents are commonly used. There are many treatments available, however it is not known which is the most effective or safest treatment option, or which is the best combination.

This review included data from 11 clinical trials involving 404 participants. The studies had very small numbers of participants, so can provide only limited information. Ten different active treatments were studied, including prednisolone, pulsed oral dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor and traditional Chinese medicine.

This review found insufficient information to conclude which is the most effective and safest treatment plan. We found that mycophenolate mofetil appears to be more effective than azathioprine in controlling disease, although no difference was seen in remission. We found that taking azathioprine and cyclophosphamide decreased the amount of glucocorticoids required. Topical epidermal growth factor decreased time required for lesions to heal by 6 days (median). We found no difference in withdrawal due to adverse events in any study, although differing adverse event profiles were observed for each intervention. We were not able to conclude which treatments are superior overall.

Multiple treatments are available for pemphigus vulgaris and pemphigus foliaceus and there is a variation in dosage plan and combination of drugs used, which makes choice of treatment schedule complex. In addition, response to treatment can vary between individuals. Treatments need to be chosen after careful consideration of the potential benefits and side effects, in the context of the individual's other medical conditions. This review found insufficient information to conclude which is the most effective and safest treatment regimen. Further studies are required to determine the optimal treatment regimen, especially to assess the optimal glucocorticoid dose, the role of adjuvant immunosuppressive medications, and long-term adverse events to improve harm:benefit analyses.

 

摘要

背景

尋常型天皰瘡及落葉型天皰瘡的治療

目前我們已經知道許多天皰瘡的治療方式，但尚未建立一種最理想的治療方式。

目標

評估尋常型天皰瘡及落葉型天皰瘡治療的效度及安全性

搜尋策略

我們搜尋了Cochrane Skin Group Specialised Register (2008年10月), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2008), MEDLINE (2003年至2008年10月), EMBASE (2005年至2008年10月), LILACS (1981年至2008年10月), 已註冊且持續進行中的試驗,文章的參考文獻,國際天皰瘡會議，以及此領域的專家。

選擇標準

有關尋常型天皰瘡及落葉型天皰瘡治療的隨機對照研究

資料收集與分析

此研究由兩位作者分別去評估研究的品質和數據。我們也聯繫了所有的評估者以獲得更多的資訊，並且包含了所有研究的不良反應。

主要結論

11個研究中,共有404位參與者 (337位尋常型天皰瘡,27位落葉型天皰瘡和40位未分類型) 。所概括的研究品質並不高，大部分的研究並沒有分組隱匿，而且效力皆受限於樣本數目很小。治療的評估包括了prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate,血漿置換,外用表皮生長因子和傳統中藥。

作者結論

到目前為止，尚未有足夠資訊來找出對於尋常型天皰瘡及落葉型天皰瘡最理想的治療方式。還需要更多的研究，來評估皮質類固醇最佳的劑量、輔助性免疫抑制劑的角色以及長期的副作用，來改善治療效果與副作用的分析結果。

翻譯人

本摘要由馬偕醫院尤彥棻翻譯。

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

總結

尋常型天皰瘡及落葉型天皰瘡的治療:這篇臨床研究回顧是為了找出尋常型天皰瘡及落葉型天皰瘡最有效且最安全的治療。這兩種罕見的疾病主要的表現為皮膚和黏膜產生易破的水泡和潰瘍。導因於身體本身產生抗體去攻擊自己的皮膚，屬於ㄧ種自體免疫疾病，是慢性且無法根治的疾病。尋常型及落葉型天皰瘡的治療是靠藥物來抑制免疫系統。治療的目的是抑制水泡的形成。系統性的皮質類固醇是天皰瘡治療的基石，其他輔助性的免疫抑制劑及抗發炎製劑也很常使用。治療上，目前有許多選擇，但哪個最有效、最安全或是最好的組合仍不確定。這篇回顧包括了11篇臨床試驗，404名受試者。但由於樣本數目很少，因此所能提供的資訊有限。。我們研究了十種不同的治療，包括了prednisolone, pulsed oral dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate,血漿置換,外用表皮生長因子和傳統中藥。本篇回顧並未找到足夠的證據來證實哪些是最有效且最安全的治療。我們發現mycophenolate mofetil比azathioprine更能有效的控制病情，但對緩解期的控制沒有差異。另外，合併使用azathioprine和cyclophosphamide 可以減少類固醇的使用量。外用的表皮生長因子可以使病灶癒合的時間平均減少6天。在所有的研究報告中，雖然每種治療都有不同的藥物不良反應，但是為此而停止用藥的情形並未有任何不同。我們沒辦法對於哪種是最好的治療來下定論。因為尋常型天皰瘡及落葉型天皰瘡有許多的治療方式，又每種治療計畫所併用的藥物和劑量又有所不同，因此讓治療計畫的決定更為複雜。除此之外，每個人對治療的反應也不盡相同。治療的選擇必需考量到可能的好處以及副作用，以及病人的其他疾病。本篇回顧沒有足夠的證據，來定論那個治療是最有效且最安全的。我們需要更多的研究來決定什麼是最理想的治療方法。尤其是去評估最佳的皮質類固醇劑量，輔助性免疫抑制劑的角色，還有長期使用下的藥物不良反應來改善治療效果與副作用的分析結果。