Treating alopecia areata

Key Points

Houston - Results of a pilot study suggest bexarotene deserves further exploration as a treatment for alopecia areata, according to investigators from the University of Texas M.D. Anderson Cancer Center.

Madeleine Duvic, M.D., discusses the outcomes from a phase 2, randomized, two-stage, bilateral comparison of bexarotene 1 percent gel (Targretin, Eisai/Ligand) in patients with alopecia areata (AA, 34 patients), alopecia totalis (AT, three patients), or alopecia universalis (AU, five patients).

After 24 weeks, 11 (26 percent) of the 42 enrolled patients achieved 50 percent or greater hair regrowth. Median time to onset of regrowth was 12 weeks, with a range between eight and 24 weeks. The disease was stable in 21 patients, and progressed in seven, while the three remaining patients were lost to follow-up.

Bexarotene gel is approved for the treatment of cutaneous T-cell lymphoma (CTCL).

The observation that hair regrowth occurred when bexarotene was used for that indication, and also when used off-label in patients with follicular mucinosis, led to the idea of investigating its potential to treat alopecia areata. There is also biologic plausibility supporting its possible efficacy.

"Alopecia areata is characterized by perifollicular and intrafollicular mononuclear cell infiltrates composed primarily of activated CD4+ and CD8+ cells, and depletion of either of these activated T-cell types in animal models of alopecia areata is associated with hair regrowth," Dr. Duvic says.

"These findings suggest a potential therapeutic role for a T-cell directed approach, and in CTCL, bexarotene has been shown to decrease T cells and induce T-cell apoptosis in lesional skin," Dr. Duvic tells Dermatology Times.

Patients were enrolled in the AA study if they were at least 18 years of age and had two distinct AA patches at least 1.0 cm in diameter on each side of the scalp or had AT or AU. Bexarotene gel treatment was initiated with once-daily application to patches on one side of the scalp, or half of the scalp in patients with AT or AU. After two weeks, the application frequency was increased to twice daily as tolerated.

The 11 responders included 10 AA patients and one patient with AT. The investigators reported that the responder rate was interestingly higher among women (10/31, 32 percent) than men (1/11, 9 percent), although any reason for the noted gender difference is unclear.

"We also saw evidence of a fascinating potential synergism between bexarotene and oral corticosteroid treatment, as one AU patient who showed no response to topical bexarotene after 20 weeks experienced rapid hair regrowth on the side of the scalp previously treated with topical bexarotene following initiation of pulsed oral prednisolone," Dr. Duvic says.

The study protocol allowed patients who responded after 24 weeks of treatment to continue in a six-month extension phase where bexarotene gel was applied to all affected areas of the scalp.

Five of the 11 responding patients continued treatment. Three went on to achieve complete responses on both sides of the scalp and one had more than 50 percent regrowth on both sides.

Topical bexarotene treatment was generally well-tolerated. The majority of patients (73 percent) experienced local irritation, but only one patient discontinued therapy because of this toxicity. Treatment was stopped temporarily because of irritation in five patients, but was then resumed.

Disclosure: The pilot study was an investigator-initiated trial funded in part by Ligand Pharmaceuticals. Dr. Duvic has been an adviser, investigator and received honoraria from Ligand/Eisai.