Minocycline for acne vulgaris: efficacy and safety

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.

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.

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.

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.

27 randomised controlled trials met the inclusion criteria and were included in this review. The comparators used were placebo (2 studies), oxytetracycline (1), tetracycline (6), doxycycline (7), lymecycline (2), topical clindamycin (3), topical erythromycin/zinc (1), cyproterone acetate/ ethinyloestradiol (1), oral isotretinoin (2), topical fusidic acid (1) 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.

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.

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.