Minocycline for acne vulgaris: efficacy and safety

 

Abstract

Background

Minocycline is a tetracycline antibiotic that is commonly used in the treatment of moderate to severe acne vulgaris. Although it is more convenient for patients to take than first-generation tetracyclines, as it only needs to be taken once or twice a day and can be taken with food, it is more expensive. Concerns have also been expressed over its safety following the deaths of two patients taking the drug. There is a lack of consensus among dermatologists over the relative risks and benefits of minocycline. As most acne prescribing is undertaken by general practitioners, it is important that guidelines issued to them are based on the best available evidence rather than personal judgements.

Objectives

To collate and evaluate the evidence on the clinical efficacy of minocycline in the treatment of inflammatory acne vulgaris. Specific objectives were to compare the efficacy of minocycline with other drug treatments for acne and to collate information on the incidence of adverse drug reactions.

Search methods

Randomised controlled trials (RCTs) of minocycline for acne vulgaris were identified by searching the following electronic databases; MEDLINE, EMBASE, Biosis, Biological Abstracts, International Pharmaceutical Abstracts, Cochrane Skin Group's Trial Register, Theses Online, BIDS ISI Science Citation Index, National Research Register, Current Controlled Trials and Bids Index to Scientific and Technical Proceedings. Other strategies used were scanning the references of articles retrieved, hand-searching of major dermatology journals and personal communication with trialists and drug companies.

Selection criteria

To be eligible for the review, studies had to be RCTs comparing the efficacy of minocycline at any dose to active or placebo control, in subjects with inflammatory acne vulgaris. Diagnoses of papulo-pustular, polymorphic and nodular acne were also accepted. Trials were not excluded on the basis of language.

Data collection and analysis

Twenty-seven randomised controlled trials met the inclusion criteria and were included in this review. The comparators used were placebo (two studies), oxytetracycline (one), tetracycline (six), doxycycline (seven), lymecycline (two), topical clindamycin (three), topical erythromycin/zinc (one), cyproterone acetate/ ethinyloestradiol (one), oral isotretinoin (two), topical fusidic acid (one) and there was one dose response study. Two studies are ongoing and it remains to be clarified whether one further study is a RCT. Major outcome measures used in the trials included lesion counts, acne grades/severity scores, doctors' and patients' global assessments, adverse drug reactions and drop-out rates. The quality of each study was assessed independently by two assessors and an effect size calculated where possible. An additional three RCTs and three safety studies were identified by searches conducted in November 2002; these will be reviewed for a major update in early 2003 when it is anticipated that the results of the two ongoing studies will be available.

Main results

The trials were generally small and of poor quality and in many cases the published reports were inadequate for our purpose. Pooling of the studies was not attempted due to the lack of common outcome measures and endpoints and the unavailability of some primary data. Although minocycline was shown to be an effective treatment for acne vulgaris, in only two studies was it found to be superior to other tetracyclines. Both of these were conducted under open conditions and had serious methodological problems. A third study showed it to be more effective than 2% fusidic acid, applied topically, against inflammatory lesions in mild to moderate acne. Differences in the way adverse drug reactions were identified could have accounted for the wide variation between studies in numbers of events reported. This meant that no overall evaluation could be made of incidence rates of adverse events associated with minocycline therapy. No RCT evidence was found to support the benefits of minocycline in acne resistant to other therapies and the dose response has only been evaluated up to eight weeks of therapy.

Authors' conclusions

Minocycline is likely to be an effective treatment for moderate acne vulgaris, but this review found no reliable RCT evidence to justify its continued use first-line, especially given the price differential and the concerns that still remain about its safety. Its efficacy relative to other acne therapies could not be reliably determined due to the poor methodological quality of the trials and lack of consistent choice of outcome measures. Similarly the relative risk of adverse drug reactions could not be ascertained reliably and no recommendations can be made concerning the appropriate dose that should be used. It is hoped that this review will highlight the inadequacy of acne trials in general and encourage improvements in methodological quality and standards of reporting.

 

Plain language summary

Minocycline for acne vulgaris: efficacy and safety

The cause of acne is not fully understood but pores in the skin become blocked and infected due to a build up of excess skin oil, bacteria and other tissue. Antibiotics reduce bacteria and inflammation and minocycline is commonly prescribed to treat acne. It is however more expensive than other similar antibiotics and there are concerns about its safety. The review found that there was no reliable evidence that minocycline was better than any other acne treatment and that more research is needed.

 

摘要

背景

minocycline對於青春痘的療效和安全性

Minocycline是一種常被用來治療中度至重度青春痘的tetracycline類的抗生素。儘管比起第一代的tetracycline類抗生素而言較為方便，具有一天只要吃一到兩次並且可以與食物一起吃的優點，它也比較貴。在有兩例服用後死亡的個案之後，其安全性也開始受到質疑。皮膚科醫師對於這個藥的風險和好處也缺乏共識。因為大部分青春痘仍是由基層醫師所處方，治療的指引應該是根據目前可得之最好証據而不是個人經驗。

目標

整理和評估minocycline在治療發炎性青春痘之臨床療效的証據。特別的目標在於比較minocycline和其他藥物治療對於青春痘的療效，並且統計不良反應的發生率。

搜尋策略

藉由搜尋以下資料庫找關於minocycline對青春痘治療的隨機對照試驗：MEDLINE, EMBASE, Biosis, Biological Abstracts, International Pharmaceutical Abstracts, Cochrane Skin Group's Trial Register, Theses Online, BIDS ISI Science Citation Index, National Research Register, Current Controlled Trials and Bids Index to Scientific and Technical Proceedings。其他還包括已搜得文章之參考文獻、人工翻閱較大的皮膚科雜誌、以及與試驗設計者和藥商的討論。

選擇標準

必須是比較任一劑量的minocycline和其他藥物或安慰劑在發炎性青春痘之療效的隨機對照試驗才能被選入本次回顧。如果診斷是丘疹膿皰性、多型性、或是結節性青春痘也可以接受。試驗不會因為語言因素而被排除。

資料收集與分析

共有27個符合條件的隨機對照試驗納入本次回顧。其比較的對象包括安慰劑 (2個試驗) 、oxytetracycline (1個試驗) 、tetracycline (6個試驗) 、doxycycline (7個試驗) 、lymecycline (2個試驗) 、外用clindamycin (3個試驗) 、外用erythromycin/zinc (1個試驗) 、cyproterone acetate/ ethinyloestradiol (1個試驗) 、口服 isotretinoin (2個試驗) 、外用fusidic acid (1個試驗) ，並有一個試驗為劑量反應研究。兩個試驗仍在進行當中，其中一個是否為隨機對照試驗仍有待確認。主要的結果評估包括病灶數目，青春痘嚴重度等級，醫師和患者的評估，不良藥物反應，和實驗退出率。試驗的品質是由兩位審查員獨立評估，並且如果可能的話計算其效用大小。另外有3個隨機對照試驗和3個安全性試驗在2002年11月的搜尋中被找到；這幾個試驗，連同先前結果尚未出來的兩個隨機試驗，會一起在2003年初的回顧中審查。

主要結論

大部份的試驗個案數都很少而且品質不佳，並且很多情況下對於我們的研究目的而言都不足夠。我們並未試著將不同試驗合併統計，因為每個試驗的結果評估方式不同，而且有一些個案的基本資料也不全。雖然minocycline對青春痘而言是有效的治療方式，但是只有在兩個試驗中，它優於其他的tetracycline藥物。這兩個試驗都是在無條件控制的狀況下進行並且有嚴重的方法問題。另外一個試驗顯示minocycline比外用2% fusidic acid在輕中度的發炎性病灶上更有效。不良藥物反應的測定方式不同，可以解釋對於不同試驗中不良反應發生率的差異。這也表示使用minocycline治療的不良反應發生率很難整體性評估。沒有隨機對照試驗可以証明對於其他治療無效的青春痘而言，minocycline是有好處的；而且劑量成效評估也只追蹤了8個禮拜。

作者結論

Minocycline對於中度青春痘應該是有效的治療，但是本次回顧找不到可信的隨機對照試驗來支持它持續作為第一線用藥的証據，尤其是考量其價格差異和安全性方面仍是有顧慮的情況下。比較起其他青春痘治療而言，minocycline的效果也難以可信的評估，因為大部份試驗的方法學品質都不好，結果評估的方式也不同。同樣地其藥物不良反應也無法可信地評估，我們無法推薦一個合適的治療劑量。我們希望藉由本次回顧能突顯整體上青春痘試驗之不足，並且改善實驗設計品質和報告的標準。

翻譯人

本摘要由馬偕醫院黃政傑翻譯。

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

總結

Minocycline對於青春痘是一個有效的抗生素治療，雖然對於其安全性仍有疑慮並且其藥價也比其他抗生素貴。雖然青春痘的形成機轉仍未完全明朗，但我們觀察到皮膚毛孔被油脂、細菌、和其他組織阻塞並感染。抗生素可以減少細菌和發炎，minocycline很常被用於青春痘的治療。然而minocycline比其他抗生素貴，而且目前對於其安全性仍有疑慮。本次回顧發現沒有足夠証據顯示minocycline比其他治療更好，我們需要更多的研究。