Effective Topical Agents and Emerging Perspectives in the Treatment of Psoriasis

Andrea Chiricozzi; Sergio Chimenti

Disclosures

Expert Rev Dermatol. 2012;7(3):283-293. 

In This Article

Topical Calcineurin Inhibitors

Topical calcinuerin inhibitors could be taken into consideration as a maintenance therapy after a satisfactory steroid therapy, possibly by reducing corticosteroids gradually and introducing calcineurin inhibitors as substitute therapeutic agents. They could constitute a valid alternative to corticosteroids because of their ability to suppress T-cell activation and proliferation. Indeed, by blocking calcineurin phosphatase, they prevent the dephosphorylation of the nuclear factor of activated T cells, which leads to inhibition of the activation of T cells and the production of proinflammatory cytokines including TNF-α, IFN-γ and IL-2, which is a key cytokine in the activation and amplification of T-cell response.[65]

Pimecrolimus (1.0%) and tacrolimus (0.03 and 0.1%) have been proven to be effective, well tolerated and safe in the treatment of atopic dermatitis, whereas their use in psoriasis is off-label, and their efficacy is still controversial.[66,67] Their efficacy seems to be limited because of their poor penetration into hyperkeratotic psoriatic plaques, and thus they might be considered as optimal therapeutic option in treating intertriginous areas and more sensitive body sites such as the face where the absorption is naturally increased.[68,69] However, in order to increase the limited penetration of these agents, they could be applied under occlusion or in combination with keratolytics such as salicylic acid and urea.

Recent clinical trials and case series showed an impressive efficacy in treating facial and flexural psoriasis. In an open-label clinical trial of 21 patients, tacrolimus induced complete clearance after 57 days of treatment in 81% of patients.[70]

A randomized, double-blinded, controlled, multicenter study enrolling 167 patients demonstrated clearance or excellent improvement in 65.2% of the tacrolimus ointment group compared with control group after an 8-week treatment period.[71]

In a study of 21 patients treated with 0.1% tacrolimus ointment, applied twice daily for 4 weeks without occlusion, 10 (47.6%) and 9 (42.9%) patients experienced a complete or good response, respectively.[72]

For the treatment of genital psoriasis, an open-label study was performed using topical tacrolimus 0.1% ointment, applied twice daily for 8 weeks with a follow-up period of 4 weeks.[68]

The other calcineurin inhibitor, pimecrolimus, has been shown to be effective and well tolerated for intertriginous and facial psoriasis. In a double-blind, randomized, vehicle-controlled study of 57 patients, 8 weeks of pimecrolimus treatment induced an improvement in 82% of patients compared with 41% of the vehicle group.

On the basis of Investigator Global Assessment, good efficacy of 1% pimecrolimus cream has also been observed in a double-blind, randomized, controlled trial involving 57 patients with moderate-to-severe inverse psoriasis. More than half of patients (54%) were clear or almost clear after 2 weeks of treatment compared with 21% of the vehicle arm, and by week 8, the percentage increased to up to 71%.[72]

Lebwohl et al. confirmed tacrolimus as being effective for the treatment of facial and flexural psoriasis, showing marked improvement in 66.7% of patients compared with 36.8% of the vehicle arm.[70]

Regarding the safety profile, calcineurin inhibitors appear to be safe, since only mild side effects including itching, stinging and the feeling of warmth may occur, and they do not show the typical long-term side effects of steroids, although no extensive studies so far have confirmed their safety in psoriasis treatment.

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