Objectives:

Acne is a common condition, particularly in adolescents and young adults, with potentially significant physical and psychological morbidity from scarring and from adverse effects of treatment, as well as significant economic burdens. The purpose of this review was to provide a comprehensive review of the literature on acne management.

Search strategy:

The following reference databases were searched: CENTRAL database of the Cochrane Collaboration (1948 through April, 1999), MEDLINE^® (1966 through April, 1999), OLDMEDLINE (1960 through 1965), PsycINFO^® (1887 through June, 1999), and CINAHL^® (1982 through June 1999). The CENTRAL search strategy was (acne-vulgaris*.me OR acne*.tw). Similar strategies were used for the other databases. The MEDLINE^® strategy combined, using a Boolean AND, a topic-specific strategy (acne vulgaris [mh] OR acne* [tw]) with a strategy designed to retrieve all controlled trials. Reference lists from key articles were hand reviewed.

Selection criteria:

In consultation with our partners and technical experts, the following questions were formulated: What treatments are effective? What is the responsiveness of first-line, second-line, and third-line treatments? What are the side effects of treatment? Controlled trials of acne therapy were sought that presented original, human data, written in English.

Data collection and analysis:

Identified articles were screened by independent reviewers in an abstract review process to determine eligibility for full article review. Eligible articles were reviewed serially by two or more abstracters who sought methodological and outcome data. The unit of analysis was the comparison between pairs of treatment arms. Comparisons were qualitatively synthesized into conclusions for which there were varying levels of evidence.

Main results:

Our searches identified 4,749 articles. After full article review, 250 articles reporting results of 274 controlled trials were included, from 31 countries. Of trials included, 74 percent reported data on subjects' age, 13 percent reported on phase of care at study entry, 8 percent reported on race, and none reported on sexual maturity rating. Investigators used 25 assessment schemes to classify acne severity, and 505 distinctly named outcomes over 4 periods of followup (usually <3 months). Two trials addressed psychological effects and 43 provided data concerning treatment compliance. None reported on cost. Only eight trials stratified results by patient demographics and none by degree or type of prior therapy. Trials that had only strengths numbered 45 (16 percent). Trials that had only weaknesses numbered 106 (39 percent). Trials that had a mix of strengths and weaknesses numbered 101 (37 percent). The remaining 22 (8 percent) were of intermediate quality or did not provide enough information to make a determination.

There were 250 pairwise comparisons of over 140 treatments. In grading the strength of evidence, there were 14 comparisons with Level A, 102 with Level B, and 134 with Level C evidence regarding effectiveness of treatment for acne. The Level A comparisons suggested the greater effectiveness of topical clindamycin, erythromycin, tetracycline, tretinoin, and norgestimate/ethinyl estradiol over vehicle in mild-to-moderate acne; the greater effectiveness of benzoyl peroxide and aluminum chlorhydroxide/sulphur over vehicle in unstated acne severity; and equal effectiveness among topical tretinoin, isotretinoin, and motretinide. The following Level A conclusions demonstrated equivalence: Benzoyl peroxide at various strengths was equally efficacious in mild/moderate acne; adapalene and tretinoin were equally efficacious in unspecificed severity; motretinide and tretinoin were equally effective; adding vitamin A to oxytetracycline conferred no added efficacy; cyproterone was equally effective at two different doses. For side effects data, 88 comparisons provided evidence for withdrawals, severe side effects, or side effects in more than 10 percent of subjects in at least one arm. There were 10 comparisons of Level A strength.

Conclusions:

Despite the large number of English-language controlled trials regarding acne therapy, their methodological limitations prevent our ability to evaluate the comparisons among therapies, and may limit the conclusions that others may draw in the future from this evidence base, even when coupled with expert knowledge. Multiple treatments, inconsistent information about baseline characteristics, and heterogeneity of assessment schemes and outcomes make it difficult to synthesize the evidence about best approaches to acne management. For future research to provide results for comparison, standardization among researchers is needed in these different areas. Research is needed to define the optimal sequence of acne therapy, and to define the relative roles of specialists and generalists in the care of acne.

This report was developed using accepted evidence-based techniques; however, as in other areas of research, the methodology was necessarily constrained by issues of feasibility and practicality so that, for example, the analysis was limited to clinical trials reported in the English language. Nonetheless, this report is a systematic effort to collect and summarize the available evidence on the management of acne and represents a potentially powerful resource for the field. As with any systematic review, to be accurate and comprehensive, the generation of guidelines requires additional information, such as expert opinion, to put the evidence into context.