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Alefacept
General information
Alefacept is a bioengineered fusion protein of soluble lymphocyte function antigen (LFA-3) with Fc fragments of IgG1. It blocks the LFA-3/CD2 interaction necessary for activation and proliferation of memory effector T cells by binding to CD2 expressed on the surface of T cells. It has been used in the treatment of psoriasis and psoriatic arthritis. There has also been a small pilot study of its use in rheumatoid arthritis [ ]. Its uses and efficacy have been reviewed [ , ].
The reported adverse effects of alefacept are generally minor and include headache, nasopharyngitis, rhinitis, influenza, upper respiratory tract infections, pruritus, arthralgias, fatigue, nausea, accidental injury, and increases in liver enzymes [ ]. A few patients develop antibodies against alefacept.
Drug studies
Observational studies
The pooled results of randomized controlled trials show that alefacept is generally well tolerated (1289 evaluable patients; 876 received alefacept, 413 received placebo). The type and frequency of adverse events were similar in the two groups. The most common adverse effect was chills, which occurred in 13% of alefacept-treated patients during the first course of treatment, starting within 24 hours of treatment and limited to one or two treatments. In phase III trials there were reductions in CD4 + T cell counts to under 250 × 10 6 /l in 10% and 5% of patients treated with alefacept once weekly for 12 weeks by the intravenous (7.5 mg) and intramuscular (15 mg) routes respectively. Opportunistic infections have not been reported, and there has been no evidence of an increased risk of infections or malignancies.
In an open study in 11 patients with active psoriatic arthritis who were given alefacept for 12 weeks the most common adverse effects that were probably or definitely associated with the drug were a flu-like syndrome (54%) and infections (18%) [ ]. There were two severe adverse events, which were both judged to be unrelated to alefacept.
Placebo-controlled studies
In a randomized, double-blind, placebo-controlled trial in 185 patients with psoriatic arthritis aged 18–70 years alefacept 15 mg or placebo was given intramuscularly once a week for 12 weeks in combination with methotrexate, followed by 12 weeks of observation during which only methotrexate was continued [ ]. Back pain and a raised alanine transaminase activity were more common than in those given placebo. Adverse events led to withdrawal of treatment in two patients taking alefacept, one because of worsening and one because of increased transaminase activities to 3–5 times the upper limit of normal; in the latter the transaminases returned to normal after withdrawal of alefacept. There were serious adverse events in two patients who received alefacept (metrorrhagia, rectocele, and emphysema) and in three who received placebo (intervertebral disc protrusion, non-infectious gastroenteritis, and breast cancer). Most of the recorded adverse events were mild to moderate in intensity and none of the serious events was attributed to the drug. There were no opportunistic infections or malignancies.
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