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    Biologic lifelines

    New drugs offer exciting treatment options for psoriasis

    Dr. Lim
    Washington - Five new biologic drugs for psoriasis offer useful alternatives when the standard therapies cannot be used, according to Henry W. Lim, M.D. Dr. Lim focused on the five biologics in his summary of the most important recent developments in medical dermatology for the American Academy of Dermatology annual meeting.

    "They are exciting new agents, that's for sure, mainly because these are a completely new class of medications," said Dr. Lim, chairman and CS Livingood chair, department of dermatology, Henry Ford Health System, Detroit. "Therefore, they offer a new set of options for the treatment of psoriasis," he said.

    The biologics break down into several categories. Tumor necrosis factor-alpha (TNF-alpha) inhibitors include: etanercept (marketed by Amgen as Enbrel), infliximab (marketed by Centocor as Remicade), and adalimumab (marketed by Abbott as Humira). There are also T-cell inhibitors, including anti-CD2 alefacept (marketed by Biogen as Amevive) and anti-CD11, an efalizumab (marketed by Genentech as Raptiva).

    Role of TNF-alpha TNF-alpha, made by many skin cells, is one link in a chain of cytokines that trigger the inflammation characteristic of psoriasis. TNF-alpha also induces growth factors involved in angiogenesis and the proliferation of keratinocytes. It may also stimulate the production of adhesion molecules involved in plaque formation.

    Etanercept is a TNF-receptor/IgGI fusion protein. It has been approved by the U.S. Food and Drug Administration (FDA) for psoriatic arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis and ankylosing spondylitis. Dr. Lim expects it to be approved for psoriasis in the near future.

    In a study reported last year in the New England Journal of Medicine (349:2014), 34 percent of patients taking 25 mg of subcutaneous etanercept twice weekly for 12 weeks experienced at least a 75 percent improvement in their Psoriasis Area and Severity Index (a PASI-75). After 24 weeks of this treatment, 44 percent of patients had a PASI-75.

    Infliximab is a chimeric antibody that binds TNF-alpha. It has FDA approval for rheumatoid arthritis and Crohn's disease. In an study reported last year in the Journal of the American Academy of Dermatology (49:s112), it was administered in an IV infusion of greater than 120 minutes at weeks 0, 2 and 8. At week 10, 82 percent of patients who received 5 mg/kg and 73 percent of patients who received 10 mg/kg achieved a PASI-75. Overall, 48 percent of patients maintained a PASI-75 at week 26.

    Adalimumab is a recombinant human IgG1 antibody specific for TNF-alpha. It has FDA approval for rheumatoid arthritis. The recommended dosage is 40 mg subcutaneous every other week.

    The TNF-alpha inhibitors all carry some risk of side effects including immunosuppression, infection, malignancy, congestive heart failure, and demyelinating disease (such as multiple sclerosis). They may cause a lupus-like syndrome, a reaction at the injection site, or infusion reaction. Also, it is important to screen patients for tuberculosis.

    T-cell inhibitors Alefacept binds to the lymphocyte antigen CD2. This interferes with the interaction between leukocyte function associated antigen (LFA)-3 and CD2, hence inhibiting T-cell activation and proliferation. The FDA approved it for psoriasis in January 2003. The recommended administration is 7.5 mg intravenous (IV) or 15 mg intramuscular (IM) each week.

    Citing an article published last year in The Medical Letter (45:31), Dr. Lim said after a 12-week IV course of alefacept, 28 percent of patients reached PASI-75. After two IV courses (12 weeks on, off and then on again) 40 percent achieved PASI-75. In a 12-week IM course, 33 percent reached PASI-75. The CD4+ T cell counts of patients on alefacept must be monitored before each dose. Side effects include infection, chills, and constitutional symptoms.

    Finally, efalizumab, which the FDA approved for psoriasis in November 2003, is a humanized monoclonal antibody against CD11a. CD11a is the alpha-subunit of LFA-1. LFA-1 is a T-cell adhesion molecule which binds with ICAM-1. By binding to CD11a, efalizumab causes decreased T-cell migration, activation, and adhesion to keratinocytes.

    In studies reported last last year in the New England Journal of Medicine (349:2004) and the Journal of the American Medical Association (290:3073), patients were given subcutaneous injections of efalizumab with 0.7 mg/kg as a conditioning dose, then 1 or 2 mg/kg (up to a maximum dose of 200 mg) per week. Of patients receiving 1 mg/kg, 22 percent achieved a PASI-75 after 12 weeks. Of those receiving 2 mg/kg, the percentage achieving PASI-75 was 28.

    Side effects of efalizumab include constitutional symptoms, infection, worsening of psoriasis, anti-efalizumab antibodies, in rare cases thrombocytopenia, and the necessity of avoiding vaccinations.

    The percentage of patients achieving PASI-75 of these biologics ranges from 30 to 80 percent after 12 weeks of therapy. In comparison, 72 to 75 percent of patients become "clear" or "almost clear" after eight to 16 weeks of therapy with narrowband UVB or PUVA. For cyclosporine, the percentage of patients achieving PASI-75 ranges from 30 to 70, and for methotrexate it is 60, he said.

    The cost of these new medications ranges from $12,000 to $24,000 a year, Dr. Lim said. But in addition to offering alternatives where older treatments have failed, he said, the new medicines can be used in rotation with the old ones, giving patients some relief from any side effects.

    The new drugs also have some unique advantages: infliximab takes effect within days, and the remission period for patients treated with alefacept ranges from seven months to more than a year. "In this context, it's exciting to have a different set of agents," said Dr. Lim.

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