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    Dosing strategies

    Threshold for biologics likely higher than thought for treating psoriasis


    Dr. Lebwohl
    Washington - The optimum doses of biologic treatments for psoriasis may be higher than previously believed, according to Mark Lebwohl, M.D., professor and chairman, department of dermatology, Mt. Sinai School of Medicine.

    Reporting on medical therapeutics at the American Academy of Dermatology annual meeting, Dr. Lebwohl cited research on the biologics as among the most important developments in recent years.

    Biologics use protein from human or animal cells to disable the immune cells involved in psoriasis. The five biologics break down into three categories.

    • Three tumor necrosis factor-alpha (TNF-alpha) inhibitors: etanercept (marketed by Amgen as Enbrel), infliximab (marketed by Centocor as Remicade) and adalimumab (marketed by Abbott as Humira).
    • A co-stimulatory pathway inhibitor: alefacept (marketed by Biogen as Amevive).
    • An anti-CD11a: efalizumab (marketed by Genentech as Raptiva).

    As of February, alefacept and efalizumab had been approved by the U.S. Food and Drug Administration for psoriasis; the others were being used for psoriasis off label.

    "With Amevive (alefacept), giving more appears to be better," said Dr. Lebwohl. He and his colleagues tried lengthening the treatment period for chronic plaque psoriasis patients with this drug. They found that there was significantly greater improvement in patients treated for 16 weeks compared to patients treated for 12 weeks, the standard period.

    "A similar study should be applied to many of the other biologics," Dr. Lebwohl said. "Doubling the doses, you get a rapid response." He recommended using 50 mg of etanercept for the first three months before stepping down to the standard dose of 25 mg. "We're getting down to better and better regimens," he said.

    But already, Dr. Lebwohl said, the biologics have clear advantages over methotrexate and cyclosporine for psoriasis. In the early days of experimentation with methotrexate, he pointed out, patients sometimes died from overdoses. It took decades to refine the regimen. By contrast, side effects of the new biologics appear to be much less serious.

    Among the most promising new biologics is adalimumab, Dr. Lebwohl added. He cited an unpublished study in which 80 percent of patients on adalimumab achieved a Psoriasis Area and Severity Index score of 75. "That's a dramatic breakthrough," said Dr. Lebwohl.

    Other therapiesDr. Lebwohl offered short bulletins on several other therapies:

    • Tacrolimus (Protopic) is relatively safe to use topically for atopic dermatitis. Tacrolimus can cause kidney and blood pressure reactions when used systemically, but it is unlikely to have these effects when used topically because so little is absorbed into the blood, he said. "Those fears stem from the fact that (topical immunomodulators) are new and people tend to exaggerate fears of new drugs. There's every reason to believe they are safer than topical corticosteroids."
    • Treating anogenital warts with imiquimod (Aldara) before surgery is much more effective than surgery alone, Dr. Lebwohl said, citing a study published in the Journal of the American Academy of Dermatology (2002; 47(4 Suppl):S212-216). In addition, he listed reports of successful treatment with imiquimod of plantar's and butcher's warts, basal and squamous cell carcinomas, Bowen's disease, actinic cheilitis, lentigo maligna, extramammary Paget's disease, porokeratosis of Mibelli, granuloma annulare, keloids and PUVA-resistant plaque in mycosis fungoides.
    • A recent outbreak at a daycare center suggests that the varicella vaccine confers only partial immunity against chicken pox, Dr. Lebwohl reported, but another study suggested that a booster may increase the vaccine's effectiveness. The daycare study, reported in the New England Journal of Medicine (2002; 347:1909-1915), found the vaccine 44-percent effective against chicken pox of any severity and 86-percent effective against moderate-to-severe chicken pox.
    • Intense pulsed light and azelaic acid are both emerging as successful treatments for rosacea, Dr. Lebwohl said.

    Dr. Lebwohl noted that he and others in the Mt. Sinai Dermatology Department have worked for many of the makers of the drugs he discussed.