Long-term use of intravenous alefacept: safety and off-treatment responses in patients who have received four or more courses of therapy

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Psoriasis is a chronic disease that often requires repeated courses of treatment to maintain satisfactory control of disease signs and symptoms. Alefacept is a fully human LFA-3/IgG1 fusion protein that inhibits T-cell activation and stimulates apoptosis of memory (CD45RO+) T cells, which have been implicated in psoriasis pathogenesis. Alefacept is the first biologic agent approved for the treatment of adult patients with chronic plaque psoriasis. The safety and efficacy of alefacept, administered as a once weekly injection (either intravenous [IV] bolus or intramuscular) for 12 weeks followed by a 12-week observation period, are well documented for 1 and 2 courses of therapy. As part of the clinical development program, patients who completed phase 2 studies were eligible to participate in an open-label extension study to determine the safety and efficacy of repeated courses of alefacept. The drug was administered at a fixed dose of 7.5 mg by 30-second IV bolus once weekly for 12 weeks followed by a 12-week observation period. Subjects may receive repeated courses of alefacept if their psoriasis recurs 12 weeks or more after therapy is completed and their CD4+ T-cell count is at or above the lower limit of normal. Efficacy is assessed by the percentage of responders (as measured by PASI score and physician global assessment), the duration of response from course to course, the time to retreatment, and the reasons for attrition from the study. Adverse events, including infection and malignancy rates, and clinical laboratory data are collected weekly during therapy and for 12 weeks after each course. This is an ongoing trial. Data through 3 courses of therapy have been previously presented and published (Lowe NJ, et al. Int J Dermatol 2003;42:224-230). Some patients have now received up to 8 courses of IV therapy. Safety and off-treatment responses will be presented for those patients who have received 4 or more courses of IV alefacept. These data will provide important information regarding longer-term use of alefacept and further define the safety profile of this selective anti-T-cell agent.