Overview of New Therapeutic Developments for Acne

Anja Thielitz; Harald Gollnick


April 13, 2009

In This Article

Topical Retinoids

Topical retinoids are important tools in the management of acne because they act against comedones and microcomedones and have direct anti-inflammatory effects. Those used in a topical form for the treatment of acne include tretinoin (all trans-retinoic acid), isotretinoin (13-cis retinoic acid), adapalene and tazarotene, whereas retinaldehyde, retinol and retinyl esters are used in cosmetic preparations. The efficacy and safety of topical retinoids were reviewed recently in a comprehensive manner.[21] The safety profile of topical retinoids differs from their systemic counterparts and is related mainly to local adverse effects, such as erythema, dryness, itching and stinging.

Retinoids influence proliferation and differentiation of cells and reverse the abnormal desquamation by increasing the follicular epithelial turnover and accelerating the shedding of corneocytes, which leads to an expulsion of mature comedones and suppression of microcomedone formation.[4] Various in vitro and in vivo studies also demonstrated direct immunomodulatory activity of topical retinoids.[22,23]

Tretinoin was the first topical retinoid for clinical use and is available as a gel (0.01, 0.025 and 0.05%), cream (0.025, 0.05, 0.1 and 0.4%), liquid (0.025, 0.05 and 0.1%), lotion (0.1%), ointment (0.05%) and compresses (0.05%). Topical tretinoin's drawback of low cutaneous tolerability was overcome by new delivery systems, including tretinoin trapped within copolymer microspheres (Retin-A Micro® gel 0.1 or 0.04%, Ortho-Neutrogena, NJ, USA)[24] or prepolyolprepolymer-2 gel or cream (Avita® 0.025%, Bertek Pharmaceuticals, NC, USA).[25] The efficacy of tretinoin microsphere 0.04% over its vehicle was confirmed recently in three double-blind, randomized, vehicle-controlled, parallel-group studies.[26] Another advantage of the micosphere formulation is the marked protection against tretinoin photodegradation, even in the presence of a strong oxidizing agent, such as BPO.[27]

Adapalene, a new synthetic third-generation topical retinoid derived from naphthoic acid, is available as a 0.1% gel, cream and solution and as a 0.3% gel (Differin®, Galderma, Sophia-Antipolis, France). Adapalene 0.3% was shown to be superior to the 0.1% concentration and the vehicle patients with mild-to-moderate acne vulgaris and its safety was confirmed in a recently performed long-term study.[28] Summarizing the data of comparative trials, adapalene 0.1% is equally effective as tretinoin 0.025% or tretinoin microsphere 0.1% gel, tretinoin 0.05% cream, tazarotene 0.1% cream or isotretinoin 0.05% gel. Adapalene 0.1% gel is better tolerated than tazarotene 0.1% gel and cream, tretinoin 0.025 and 0.05% gel, tretinoin 0.05% cream, tretinoin microsphere 0.1% gel or isotretinoin 0.05% gel.[29] Once-daily therapy with adapalene 0.3% gel provided similar efficacy to tazarotene 0.1% gel in the treatment of acne vulgaris, but demonstrated a superior tolerability profile.[30]

Topical tazarotene, approved for acne treatment only in the USA (Tazorac®, Allergan Inc. CA, USA), has shown therapeutic efficacy compared with its vehicle as a 0.1% gel or 0.1% cream in large multicenter, double-blind studies involving 375 and 847 subjects, respectively.[31,32] Comparative trials showed superior efficacy of tazarotene 0.1% gel compared with tretinoin 0.025% gel and tretinoin 0.1% microsponge gel in the reduction of noninflammatory lesions and overall disease severity.[29] Compared with adapalene 0.1% gel, treatment with tazarotene was associated with significantly greater reductions in overall disease severity, noninflammatory lesion count and inflammatory lesion count.[29] Furthermore, the efficacy and safety of a short-contact regimen of tazarotene 0.1% gel applied once or twice daily compared with its vehicle has been demonstrated.[33] In this study, the subjects were instructed to adjust the contact time as tolerated between 30 s and 5 min.

Topical tretinoin and adapalene are labeled US FDA Pregnancy Category C, which means that a risk cannot be ruled out because data in humans are lacking and animal studies are either positive or data are also lacking. They may be prescribed when the benefits outweigh the risks; however, administration during pregnancy is hard to justify because alternative treatments, such as erythromycin, azelaic acid or BPO, are available. During lactation, avoidance is advised, because excretion via breast milk has not been studied and adverse reactions in nursing infants have not been ruled out. Safety and affectivity in children below the age of 12 years have not been established.

Since oral isotretinoin is a potent teratogen and designated Pregnancy Category X, the use of topical isotretinoin is contraindicated during pregnancy and lactation, and should be used with caution in women of childbearing potential.

Tazarotene is also designated Pregnancy Category X, prohibiting its use during pregnancy and breastfeeding. Women of childbearing potential should use adequate birth-control measures when topical tazarotene is used.


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