New and emerging drugs for the treatment of acne vulgaris in adolescents

ABSTRACT

Introduction: Acne vulgaris is the most common skin disease worldwide, yet current treatment options, although effective, are associated with unwanted side effects, chronicity, relapses and recurrences. The adequate control of the four pathogenic mechanisms involved in the appearance of acne lesions is key to treatment success. This paper aims to discuss the novel treatment modalities that have surfaced in consequence of new knowledge obtained in acne pathogenesis.

Areas covered: Pathogenic pathways are evaluated and discussed throughout the paper in relation to the mechanisms of action of novel molecules being investigated for the treatment of acne vulgaris. A comprehensive search was made in PubMed and Clinicaltrial.gov using a different combination of keywords, which included acne vulgaris, treatment, therapy, and therapeutic.

Expert opinion: In the near future, more effective treatments with less side effects are expected. The use of topical anti-androgens, coenzyme-A carboxylase inhibitors, and insulin growth factor-1inhibitors to control sebum production seem promising. Selective RAR-agonists have the potential of becoming an alternative to the currently available retinoid therapy in the management of infundibular dyskeratosis with a better safety profile. Antibiotic use will probably decline as more effective options for controlling Cutinebacterium acnes colonization and the inflammation cascade emerge.

KEYWORDS:

• Acne vulgaris
• novel therapies
• sebogenesis
• cutinebacterium acnes
• retinoids

Article highlights

• Four major factors have been implicated in the appearance of acne lesions: (1) altered sebum production, (2) abnormal keratinization within the pilosebaceous unit, (3) Cutinebacterium acnes (C.. acnes) colonization and (4) peri-follicular inflammation.

• Past knowledge on the pathogenesis of sebum production was sparse and was thought to be mainly a consequence of androgenic stimuli. However, recent findings have determined that other hormones such as α-melanocyte-stimulating hormone (α-MSH) and insulin growth factor-1 (IGF-1) also play a role.

• Skin sebogenesis is further controlled by acetyl coenzyme-A carboxylase (ACC), the endocannabinoid system and the presence of pro-inflammatory mediators, such as leukotriene B4 (LTB4). These new findings have opened an array of possibilities for new treatment targets.

• Current treatment strategies to limit hyperkeratinization include topical dual retinoic acid receptor (RAR)-β and RAR-γ agonists, which can cause side effects such as irritation, erythema, desquamation, and dryness, amongst others. New treatment strategies are focused on increasing RAR-γ specificity to limit side effects.

• Due to the growing concern over bacterial resistance, antibiotic use will decline over the next years and will be substituted by bactericidal agents, such as nitric oxide releasing creams, antimicrobial peptides, and agents that modulate C. acnes population, such as probiotic creams and biofilm matrix degradation gels.

• P. acnes population needs to be effectively controlled because it has been associated with direct IL-1α, IL-β, TNFα, metalloproteinase secretion, neutrophil migration and inflammation, which in turn is associated with scarring and sequels. Drugs that modulate the inflammatory response such as leukotriene inhibitors, monoclonal antibodies, and nicotinamide are currently being evaluated for the treatment of acne.

Declaration of interest

The author declares that they have served as a medical consultant for More Pharma Corporation in the past. They have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee declares having received research, speaking and/or consulting support from a variety of companies including Galderma, GlaxoSmithKline/Stiefel, Almirall, Leo Pharma, Bristol-Myers Squibb, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Ortho Dermatology, AbbVie, Samsung, Janssen Pharmaceuticals, Eli Lilly and Company, Menlo, Merck & Co, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate and National Psoriasis Foundation. Another referee, meanwhile, declares that they are/have been a researcher, consultant, and speaker for many companies who have products that treat acne, including Galderma, Almirall, Ortho Dermatology as well as a researcher and consultant for other treatments in development such as Foamix and BiopharmX. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Supplementary material

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Additional information

Funding

This manuscript was not funded.