Medical Dermatology

WAILEA, HAWAII — What do alopecia areata, psoriasis, severe chronic hand dermatitis, and mycosis fungoides have in common?

All are diseases in which T-cell activation figures centrally in the pathogenesis. And all four appear to respond to bexarotene gel (Targretin), Dr. Marie-France Demierre said at the annual Hawaii Dermatology Seminar sponsored by the Skin Disease Education Foundation.

"More studies are needed, but I believe that this molecule has a bright future in dermatology," observed Dr. Demierre of Boston University.

Bexarotene is a rexinoid. Unlike retinoids, whose cellular effects are largely confined to cell proliferation and differentiation, the rexinoids also affect inflammation and apoptosis. The rexinoids downregulate a large number of antiapoptotic genes while upregulating proapoptotic and cell differentiation-related genes as well as numerous cytokines, she explained.

Bexarotene gel's sole Food and Drug Administration-approved indication is treatment of skin manifestations of cutaneous T-cell lymphoma. But there are positive data available from phase I and II studies of several other tough-to-manage dermatoses such as:

▸ Alopecia areata. In an ongoing left/right comparison study led by Dr. Madeleine Duvic of the University of Texas, Houston, 7 of 21 severely affected patients have responded with greater than 50% hair regrowth on the Targretin-treated side. The treatment regimen consists of daily bexarotene gel to half of the scalp for 2 weeks, then twice a day out to 24 weeks.

▸ Psoriasis. Investigators at the Robert Wood Johnson Medical School, New Brunswick, N.J., recently reported on a randomized, double-blind, vehicle-controlled left/right comparison trial involving narrowband UVB phototherapy plus either bexarotene gel 1% or vehicle in 9 patients with moderate to severe psoriasis vulgaris. The pilot study entailed topical therapy twice a day for 10 weeks, with phototherapy starting 2 weeks into the trial.

Bexarotene-treated lesions displayed a mean 68% decrease in severity scores, compared with baseline. This was significantly better than the 48% reduction in target lesion scores with vehicle plus narrowband UVB. The reduction in the induration component of the lesion severity score with bexarotene was statistically significant, while the changes in the other components of the score—scaling and erythema—were not (J. Am. Acad. Dermatol. 2006;54:115–8).

In a separate soon-to-be-published study, another group of investigators reported that 15 of 24 patients with mild to moderate plaque psoriasis involving not more than 15% of their body surface area had a significant favorable response to 16 weeks of open-label bexarotene gel 1%. Dosing was escalated weekly from once to twice daily and could continue to up to four times daily. Two of 24 patients showed 100% improvement by physician's global assessment, 4 had 91%–99% improvement, another 4 had 76%–90% improvement, and 5 patients showed 50%–75% improvement.

▸ Chronic severe hand dermatitis. Dr. Jon M. Hanifin, a professor of dermatology at Oregon Health and Science University, Portland, randomized 55 severely affected patients who had failed multiple prior therapies to bexarotene gel monotherapy or to bexarotene plus either mometasone furoate or hydrocortisone in 2:1:1 fashion. The steroids were applied twice a day, while Targretin dosing was escalated from once to thrice daily.

The primary study end point—at least 90% improvement by physician's global assessment—was achieved in 39% of the Targretin monotherapy group, which wasn't significantly different than the 46% rate with Targretin plus mometasone. The rate in the Targretin plus hydrocortisone group was 21%. The secondary end point—at least 50% improvement—was achieved in 79% of those on Targretin monotherapy, 77% with the rexinoid plus mometasone, and 50% with Targretin and hydrocortisone. Mean time to at least 50% improvement was 7.7 weeks. Irritant hand dermatitis responded best, but atopic dermatitis also responded (Br. J. Dermatol. 2004;150:545–53).

Dr. Demierre noted that Targretin's lack of immunosuppressive effects is advantageous. And although the topical agent is often said to be irritating, in a head-to-head comparison study it was threefold less so than tretinoin, fivefold less so than tazarotene, and about equally as irritating as adapalene.

Dr. Demierre is a consultant to Ligand Pharmaceuticals Inc. The SDEF and this news organization are wholly owned subsidiaries of Elsevier.

04/01/06  

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