New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne Group

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The Global Alliance to Improve Outcomes in Acne published recommendations for the management of acne as a supplement to the Journal of the American Academy of Dermatology in 2003. The recommendations incorporated evidence-based strategies when possible and the collective clinical experience of the group when evidence was lacking. This update reviews new information about acne pathophysiology and treatment–such as lasers and light therapy–and relevant topics where published data were sparse in 2003 but are now available including combination therapy, revision of acne scarring, and maintenance therapy. The update also includes a new way of looking at acne as a chronic disease, a discussion of the changing role of antibiotics in acne management as a result of concerns about microbial resistance, and factors that affect adherence to acne treatments. Summary statements and recommendations are provided throughout the update along with an indication of the level of evidence that currently supports each finding. As in the original supplement, the authors have based recommendations on published evidence as much as possible.

Introduction

In 2003, a group of physicians and researchers in the field of acne, known as the Global Alliance to Improve Outcomes in Acne, published recommendations for the management of acne.1 The goal was to make recommendations that were evidence based when possible and that included input from numerous countries. Since the initial meeting of the Global Alliance in 2001, the group has continued to meet regularly to discuss various aspects of acne management and create educational initiatives for dermatologists around the world. Regional groups in Europe, Asia, and Latin America have been established. Global Alliance members have actively worked with national dermatology societies to formulate guidelines for management of acne that take into account the individual characteristics of the country while harmonizing with the international recommendations. In addition, the Global Alliance presented a written consensus opinion to the US Food and Drug Administration (FDA) Guidance for Industry on Acne Vulgaris (Docket No. 2005D-0340) regarding development of drugs for acne and design of clinical trials in this arena. A subgroup of European members of the alliance formulated a response to recent changes in the European Union regulations for use of oral isotretinoin. As new issues come up, the alliance will continue to advocate for clinicians who treat patients with acne and the patients' rights to optimal treatment. Finally, the Global Alliance has established a World Wide Web site (www.acneglobalalliance.org), which provides information about the management of acne and recent developments in the field.

The first publication in 2003 encompassed current information about acne pathophysiology and comprehensive treatment recommendations. This edition includes updates on pathophysiology and treatment, including our research into treatments that have recently emerged–such as lasers and light therapy–and areas where published data were sparse in 2003 but are now available, including combination therapy, revision of acne scarring, and maintenance therapy. In addition to an updated discussion of acne pathophysiology and treatment, we share in this supplement a new way of looking at acne as a chronic disease, a discussion of the changing role of antibiotics in acne management, and factors that affect adherence to acne treatments. As in the original supplement, we have tried to base recommendations on published evidence as much as possible. However, it should be noted that some recommendations are based primarily on our expert opinion (level V evidence) because of a lack of studies and different designs and methodologies of existing studies. We have strived to clearly acknowledge in text which recommendations are based primarily on opinion, citing them as supported by Level V evidence.

In addition, a number of the clinical trials included in our evaluations of data were performed as registration trials for regulatory approval. We acknowledge that a particular type of patient is selected for study and results may not be generalizable to all patients; regulatory bodies typically address this in the package insert. In acne, the registration trial study inclusion and exclusion criteria often exclude patients with cystic acne (>2 nodules or cysts), truncal acne is often not evaluated, and minimum and maximum numbers of inflammatory and noninflammatory lesions at baseline are specified to give an objective measure of acne severity. To our knowledge, there are no data suggesting that acne in various population subgroups–adolescent, adult, male, female–is different in terms of pathophysiology with the exception of a greater effect of hormones in female patients. Assessment of population differences would be an interesting topic for future studies.

In the case of acne, monotherapy is used relatively rarely despite that regulatory bodies require monotherapy studies for drug approval. Because acne is a multifactorial disease, multiple classes of drugs are typically used in the clinical setting. Indeed, combination therapy is now recommended as the first-line approach for acne.1 In this publication, the Global Alliance group considered the type and severity of acne in making recommendations. The Global Alliance plans to publish additional articles on the topics of hormonal/antiandrogenic therapy and the current use of oral isotretinoin.

The following definitions were used to evaluate the strength of the evidence for recommendations in the supplement:

  • I—Strong evidence from systematic review of multiple well-designed, randomized, controlled trials;

  • II—Strong evidence from at least one properly designed, randomized, controlled study of appropriate size;

  • III—Evidence from well-designed trials without randomization, single group pre/post, cohort, time series, or matched case-controlled studies;

  • IV—Evidence from well-designed nonexperimental studies from more than one center or research group;

  • V—Opinions of respected authorities, based on clinical evidence, descriptive studies, or reports of expert committees.

Section snippets

Recognizing the chronicity of acne

Editor's note: This section summarizes ideas that were presented in full in a recent article in the American Journal of Clinical Dermatology.2

It is important for dermatologists to take the lead in educating other clinicians that acne is often a chronic disease and not just a self-limiting disorder of teenagers. For many patients, acne has the following characteristics that have been used to define chronicity3, 4: a prolonged course, a pattern of recurrence or relapse, manifestation as acute

Update: Pathogenesis of acne

More detailed information regarding the molecular events contributing to the pathogenesis of acne has emerged since 2003. There are 4 primary pathogenic factors, which interact in complex manner to produce acne lesions: (1) sebum production by the sebaceous gland; (2) P acnes follicular colonization; (3) alteration in the keratinization process; and (4) release of inflammatory mediators into the skin. Now, cellular culture studies have provided more information about the role of sebaceous

Update: Treatment of acne

Several aspects of acne management have been evolving since the 2003 Global Alliance recommendations.1 These include the role of antibiotics in treatment, use of lasers and light-based therapies, issues regarding maintenance therapy, and treatment of acne scars. There is increased evidence supporting the recommendation of a combination of a topical retinoid plus an antimicrobial agent as first-line therapy for most patients with acne as a means of targeting multiple pathogenic features and both

Optimizing adherence with acne therapy

Acne medications should be started soon after the appearance of acne lesions to minimize the potential for physical and emotional scarring. This is especially important because the clinical severity of acne does not correlate well with the impact on the patient; thus, the patient may feel significant embarrassment, anger, or other psychologic disturbance even when disease is mild.230, 231, 232 Several studies have demonstrated that the impact of acne on the quality of life of adult patients is

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    Supported by an educational grant from Galderma International.

    Disclosure: Dr Berson has served on advisory boards for Galderma, Kao, Stiefel, Dusa, Johnson & Johnson, and Ortho Neutrogena and received honoraria. Dr Bettoli has served as an investigator for Galderma, Intendis, Astellas, and La Roche Posay and a speaker for Galderma, Intendis, Astellas, Stiefel, and La Roche Posay and received grants in compensation. Dr Dréno has served on advisory boards for Galderma, La Roche Posay, and Expansicone and has been a speaker for Pierre Fabre and an investigator for Biollevis and received honoraria. Dr Finlay has served on advisory boards and as speaker for Galderma and Pierre Fabre and on advisory boards for York Pharma and has received grants or honoraria. Dr Goh has served as a consultant to Galderma and received travel grants. Dr Gollnick has served as an investigator and speaker for Schering, Stiefel, and Galderma, and on advisory boards for Galderma; in addition, he has been a consultant to Basilea and IMTM and has received honoraria for these duties. Dr Herane has served as an investigator for Bioderma, Vichy, and Isden and a speaker for Galderma and Stiefel and has received honoraria and other financial benefits for this work. Dr Kang has served as an investigator and consultant for Galderma and an investigator for Stiefel and has received honoraria or grant support. Dr Kubba has served as a consultant to Galderma and Schering-Plough and in another capacity for Ranbaxy and Janssen-Cilag and has received grants and honoraria. Dr Layton has served as an advisor, speaker, and investigator for Galderma and received grants and gravel grants and has also been an investigator for Roche, receiving grants. Dr Leyden has served as a consultant and on advisory boards for Allergan, Galderma, Obagi, SkinMedica, Medicis, and Stiefel and received grants and honoraria. Dr Miyachi has served on advisory boards for Galderma, Otsuka, and Sanofi-Aventis and has received grants and honoraria. Dr Piquero Martin has served as a speaker for Galderma and received benefits. Dr Ramos-e-Silva has served on advisory boards for Galderma, Johnson, Stiefel, Novartis, La Roche Posay, and Roche; she has been an investigator for Galderma, Johnson, Stiefel, Novartis, La Roche Posay, Biolab, Aventis, and Pfizer, and has been a speaker for Galderma, Johnson, Stiefel, Novartis, LaRoche Posay, Vichy, and Roche and has received honoraria or grant support. Dr See has received honoraria as a speaker for Galderma and L'Oreal. Dr Shalita has served as a consultant to Galderma, Stiefel, Allergan (including consultancies to companies acquired by these companies), Baxbier, Quinoa, and Ortho and has been an investigator for Galderma, Stiefel, and Allergan and has received grants and honoraria; he has stock options in Medicis. Dr Shear has served on advisory boards for Galderma, and as a consultant and other for Galderma and has received honoraria and residency or fellowship program funding; Dr Shear has also served as a consultant and other for Dermik and received honoraria and residency or fellowship program funding. Dr Torres Lozada has been a consultant and investigator for Galderma and has received honoraria. Dr Wolf has been an investigator for Galderma and Medicis, an advisory board member, consultant, and speaker for Galderma and Medicis, an advisory board member and consultant for QLT, and a speaker for Stiefel and Dermik; he has received grants and honoraria and has stock in Medicis. Drs Kaminsky, Perez, and Thiboutot have no conflicts of interest to declare.

    Preparation of the manuscript was a joint effort as follows. The manuscript outline, content development and selection of references, review of the data, and generation of the first draft were done in sections, with responsibilities as follows. “Recognizing the chronicity of acne” section: Drs Shear, Finlay, and Gollnick, and Ms Sanders. “Update: Pathogenesis of acne” section: Drs Thiboutot, Kang, and Gollnick, and Ms Sanders. “Update: Treatment of acne” was further subdivided into the following sections. “The changing role of antibiotics in managing acne” section: Drs Layton, Bettoli, Miyachi, Dréno, Perez, and Leyden, and Ms Sanders. “Retinoid-based combination therapy for acne” section: Drs Thiboutot, Kaminsky, Gollnick, Miyachi, Wolf, Herane, and Piquero Martin, and Ms Sanders. “Does enough evidence now exist for using lasers and lights to treat inflammatory acne?” section: Drs Leyden, Berson, Kang, See, Shalita, Torres Lozada, and Gollnick, and Ms Sanders. “The role of topical retinoids in acne maintenance therapy” section: Drs Gollnick, Bettoli, Thiboutot, and Leyden, and Ms Sanders. “Management of acne scarring” section: Drs Dréno, Goh, Kubba, Ramos-e-Silva, and Bettoli, and Ms Sanders. “Optimizing adherence with acne therapy” section: Drs Thiboutot, Dréno, Layton, Herane, and Dr Perez, and Ms Sanders. Ms Valerie Sanders is a medical writing consultant to Galderma International. Changes to the first draft and subsequent drafts were generated by each of the authors. All authors reviewed the complete final draft including all sections.

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