Adapalene

Adapalene (Differin®) is a retinoid agent indicated for the topical treatment of acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two days; however, the drug was less effective than once-daily 0.1% tazarotene gel. It can be used alone in mild acne or in combination with antimicrobials in inflammatory acne and has proved efficacious as maintenance treatment. Adapalene has a rapid onset of action and a particularly favourable tolerability profile compared with other retinoids. These attributes can potentially promote patient compliance, an important factor in treatment success. Adapalene is, therefore, assured of a rolein the first-line treatment of acne vulgaris.

Adapalene is a chemically stable derivative of naphthoic acid that binds selectively to the nuclear retinoic acid receptor (RAR) subtypes RARγ (found mainly in the epidermis) and RARβ (found in dermal fibroblasts), activating genes responsible for cellular differentiation; it does not bind to cytosolic retinoic acid binding proteins. Adapalene is thought to modulate keratinisation, differentiation and inflammation of follicular epithelial cells. This results in a reduction in microcomedones, the precursors of acne lesions.

Across several endpoints (including the mean percentage reduction in the number of inflammatory and noninflammatory lesions), 0.1% adapalene gel had similar efficacy to 0.025% tretinoin gel, 0.05% tretinoin cream and 0.05% isotretinoin cream as well as the newer 0.1% tretinoin microsphere gel formulation in the treatment of mild-to-moderate acne vulgaris. Data were from predominantly multicentre, randomised, single- or double-blind, parallel-group trials. After 8–12 weeks’ treatment, the percentage reductions in lesion counts were 47–75% and 38–73% for adapalene and 0.025% tretinoin gel treatment groups (inflammatory lesions), respectively, and 46–83% and 33%–83% (noninflammatory lesions). The similar efficacy of these two treatments was confirmed by two meta-analyses. The onset of action with 0.1% adapalene gel is rapid and generally appears to be similar to that with tretinoin formulations.

In two randomised, double-blind, parallel-group studies, patients with mild-tomoderate acne vulgaris receiving 0.1% tazarotene gel once daily had significantly greater reductions in inflammatory and noninflammatory lesions than 0.1% adapalene recipients. The same dosage of 0.1% adapalene gel showed similar efficacy to that of 0.1% tazarotene gel once every two days (dosage reduced to improve tolerability) in another trial of the same design.

Data indicate that 0.1% adapalene gel is effective in combination with topical clindamycin or benzoyl peroxide or oral cyclines (lymecycline, minocycline) in reducing the number of inflammatory and noninflammatory lesions in patients with mild-to-moderate or moderate to moderately severe acne vulgaris. Furthermore, 0.1% adapalene gel was effective as maintenance treatment following treatment with clindamycin plus adapalene.

Adapalene was generally better tolerated than comparators, particularly in the first 4 weeks of treatment. The most commonly reported adverse events in both adapalene and comparator recipients were erythema, dry skin, pruritus, desquamation and stinging/burning sensations. These were generally less severe in adapalene recipients than in the recipients of other topical retinoids.

Several randomised, intraindividual patch studies in healthy volunteers found 0.1% adapalene gel was the least irritating acne treatment when compared with various concentrations of tretinoin gel, cream, the new formulation of tretinoin (0.1% and 0.04% tretinoin microsphere gel) or with tazarotene gel.

When used as adjunctive therapy with topical clindamycin or oral lymecycline, 0.1% adapalene gel was generally well tolerated compared with gel vehicle plus the respective antibacterial agent. Overall, local cutaneous adverse events were mild in intensity.