An Experimental Ointment Formulation of Pimecrolimus is Effective in Psoriasis without Occlusion

Abstract

Pimecrolimus (Elidel, SDZ ASM 981), a new macrolactam ascomycin derivative, was highly effective in treating plaque-type psoriasis when applied under Finn-chamber occlusion. A two-centre, randomized, double-blind, vehicle- and positive-controlled within-patient study was therefore conducted in 23 adult psoriasis patients. Pimecrolimus 1% was applied, twice daily, in an experimental ointment formulation, along with the corresponding vehicle, 0.005% calcipotriol ointment and 0.05% clobetasol-17-propionate ointment to test sites without occlusion for 21 days. Erythema, induration and scaling (score: 0 [absent] to 4 [severe]) were evaluated. The total sign score was defined as the sum of the erythema, induration and scaling scores (range 0-12). Pimecrolimus 1% ointment was significantly (p = 0.03) more effective than the corresponding vehicle, with an improvement in total sign score of 51.4% compared with 36.7% for the corresponding vehicle. Improvements with calcipotriol and clobetasol-17-propionate were 71.5% and 88.3%, respectively. No local or systemic drug-related side effects were observed in the study. We conclude that pimecrolimus 1% in the experimental ointment formulation was significantly more effective than its corresponding vehicle, but less effective than calcipotriol and clobetasol ointment. This is the first study reporting a significant therapeutic effect of pimecrolimus in an ointment formulation applied without occlusion to psoriatic plaques.

Potential New Indications of Topical Calcineurin Inhibitors

“…One may speculate that when used under occlusion with plastic films or hydrocolloid dressings, sufficient penetration may occur to have a clinically relevant therapeutic effect. Recently, a new, experimental formulation of topical pimecrolimus was shown to be more effective than placebo for the treatment of plaque psoriasis without occlusion [10] . In addition, there have been some published case studies and results from trials concerning the use of oral and topical formulations of pimecrolimus and tacrolimus in patients with this condition [9, 26,84] , and there is increasing interest in the role of newer formulations of TCIs in the treatment of psoriasis [85][86][87][88] .…”

“…TCIs are large lipophilic molecules with molecular weights between 810 and 820 Daltons, and cutaneous penetration in the absence of occlusion is lowest in areas where the epidermis is thick, such as the palmo-plantar region, as well as in skin diseases associated with marked epidermal thickening, such as plaque psoriasis [9][10][11] . Conversely, the efficacy of TCIs is greatest on areas of skin with a relatively thin epidermis that are particularly vulnerable to damage such as the face, neck, flexures, and genital areas.…”

Nanostructured lipid carrier-loaded hyaluronic acid microneedles for controlled dermal delivery of a lipophilic molecule

“…Many lipophilic drugs are therefore commercially available as creams and/or ointments. [29][30][31] Nevertheless, controlled delivery and localization of the drug to dermal layers are still necessary. MNs can deliver the drug with high efficiency in a controlled or sustained release pattern.…”

Pimecrolimus 1% Cream in the Treatment of Facial Psoriasis: A 16-Week Open-Label Study

“…In light of these observations, we have to consider the possibilities of additional delivery systems for pimecrolimus in the topical treatment of psoriasis. Other studies suggest new galenical formulations with 10% urea as a penetration-enhancing compound to increase absorption into the skin [18]. …”

“…It has been shown to be effective in treating inflammatory diseases and gained approval for topical therapy of atopic dermatitis by the US Food and Drug Administration and the European Medicines Agency [13,14,15,16]. In addition, pimecrolimus was also effective in plaque-type psoriasis when applied under occlusion and, recently, in a special ointment formulation also without occlusion [17, 18]. Recently, several case reports have provided further evidence for the beneficial effects of topical pimecrolimus and tacrolimus in the treatment of intertriginous and facial psoriasis [5,6,7, 12, 19].…”