|Management of acne
|Lehmann H P, Andrews J S, Robinson K A, Holloway V L, Goodman S N
To provide a comprehensive review on the management of acne.
The search utilised several electronic databases from inception to 1999, including the CENTRAL Register in the Cochrane Library, MEDLINE, OLDMEDLINE (from 1960 to 1965), EMBASE, CINAHL and PsycINFO amongst others. Details of the searches were given in the report. In addition, the reference lists from key articles were checked and key experts were consulted. Only full articles published in English were eligible for the review.
Study designs of evaluations included in the review
Only randomised controlled trials (RCTs) or quasi-RCTs were considered for the review. There were 259 (94%) studies of a parallel-group design, 15 (5%) crossover, 30 (11%) 'split-face', and 22 (8%) parallel studies with matched controls.
Specific interventions included in the review
Studies of first-, second- and third-line treatments for acne were eligible for inclusion in the review. The included studies were of 140 different treatments, which were classified as: cleansers, keratolytics, topical antibacterials, keratolytic/topical antibacterial combinations, topical retinoids, topical antibacterial/retinoid combinations, oral antibacterials, oral antibacterial/keratolytics, oral antibacterial/topical retinoids, oral retinoids, anti-androgens and other. All individual treatments are listed in the review. No single control intervention was specified as an inclusion criterion; 250 different pairwise comparisons were included in the review.
Participants included in the review
Patients with acne were included in the review. Studies of patients with complicating co-morbidities such as endocrinopathies, and specifically, chloracne, rosacea, acne venanta, acne fulminans and acne necroticans, were excluded. Studies from primary care, dermatology clinic and self-treatment (community) settings were included. Studies were classified by the level of acne severity at enrolment. The mean age was 21 (standard deviation 5) years.
Outcomes assessed in the review
The inclusion criteria for the outcomes were not specified. Twelve studies were excluded because they used surrogate outcome measures. The outcomes reviewed covered the categories of acne, adverse effects, psychological effects and compliance. The acne outcomes evaluated were very varied and included the physician's assessment of overall change, patient's assessment of overall change, and percentage change or count of specific aspects of the condition (e.g. inflammation, pustules, papules, comedones, severity). Those outcomes accounting for just over half of those reported in the included studies are listed in the report.
How were decisions on the relevance of primary studies made?
Decisions on selecting the studies were made by two reviewers. Any discrepancies were resolved by a third reviewer.
Assessment of study quality
Quality was assessed in terms of research design, treatment allocation, blinding, objectivity of measurements, withdrawals, analysis, and the potential for bias and generalisability. The form used for this assessment is given in the review. The quality assessment was performed by one reviewer and checked by a second.
The data were extracted by one reviewer and checked by a second. The form used for this assessment is given in the review. The reviewers attempted to standardise the definition of severe acne so that more accurate comparisons could be made between treatments. The classification system used is given in the review.
Methods of synthesis
How were the studies combined?
A narrative synthesis of the data was undertaken, focusing on pairwise comparisons. The evidence for any comparison was assessed as level A (at least two trials of acceptable quality), level B (weaker evidence, e.g. only one trial) or level C (poor or conflicting evidence). Full definitions for levels A, B and C are given in the report.
How were differences between studies investigated?
The studies and their findings were described and discussed by class of intervention, as well as by individual interventions.
Results of the review
A total of 274 controlled trials from 31 countries were identified. There were 250 pairwise comparisons of 140 treatments. The total number of participants was not stated.
The literature was extremely heterogeneous. Of the 250 comparisons, only 14 had level A evidence. These comparisons demonstrated the efficacy over placebo or inactive vehicle of the following: aluminium chlorhydroxide/sulphur, topical clindamycin, topical erythromycin, benzoyl peroxide, topical isotretinoin, tretinoin, oral tetracycline, and norgestimate/ethinyl estradiol. Level A evidence of equivalence between treatments was found for various strengths of benzoyl peroxide, adapalene and tretinoin, motretinide and tretinoin, two different doses of cyproterone, and oxytetracycline with and without vitamin A.
There were 102 comparisons with level B evidence and 134 with level C evidence. No useful data were available on whether the treatments were used first-, second- or third-line. In addition, there was no basis for relating efficacy with sequence of therapy.
Eighty-eight primary comparisons of side-effects were identified and of these 10 (or possibly 5) had level A evidence, primarily of local adverse reactions of retinoids. Clindamycin and erythromycin were equal in terms of withdrawals related to side-effects. It should be noted that there is some discrepancy in the report with one table (table 17) having only 5 level A comparisons.
This report represents a potentially powerful resource for the field of acne management. Despite the large number of controlled trials, their methodological weaknesses may limit the conclusions that others can draw from this evidence-base.
This review addressed a clinically important question using appropriate, but very broad inclusion criteria. Consequently, a large number of interventions were eligible for inclusion in the review, which resulted in an enormous review with little depth. The search strategies for published papers were thorough, but the exclusion of studies not published as full papers and the restriction to English language papers most certainly meant that relevant studies were missed. The review methodology appeared to be acceptable, although it was not always clearly described in the report. The quality of the studies was assessed and this assessment was used to inform the review findings. The narrative pooling of the study findings was appropriate, and assigning levels of evidence for identifiable comparisons was a particularly useful method of summarising the findings. Given the size and scope of this review, its findings cannot be adequately presented in an abstract and readers are referred to the report for information on particular comparisons or interventions. The authors' conclusions regarding the utility of their report and the conclusions based on level A evidence are supported by this review.
Implications of the review for practice and research
Practice: The authors did not draw any specific conclusions as to which treatments are effective. They referred readers to package inserts for information on potential side-effects.
Research: The authors make many recommendations regarding future research. Briefly, many interventions and comparisons need to be subjected to good-quality RCTs. Methodological issues such as the standardisation of baseline characteristics and optimal outcome measures need to be addressed. Research is needed to define the best sequence for therapy and to establish the relative roles of specialist and generalists in acne management.
Agency for Healthcare Research and Quality, contract number 290-97-006.
Lehmann H P, Andrews J S, Robinson K A, Holloway V L, Goodman S N. Management of acne. Rockville, MD, USA: Agency for Healthcare Research and Quality. Evidence Report/Technology Assessment; 17. 2001
Subject indexing assigned by CRD
Acne Vulgaris; Anti-Bacterial Agents /therapeutic use; Benzoyl Peroxide /therapeutic use; Dermatologic Agents /therapeutic use; Isotretinoin /therapeutic use; Retinoids /therapeutic use
Date bibliographic record published
Date abstract record published
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.