Alefacept

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Amevive (Biogen-Idec)

vials containing 7.5 mg and 15 mg as powder for reconstitution

Approved indication: chronic plaque psoriasis

Australian Medicines Handbook section 8.6

Some patients with severe psoriasis will require systemic treatment to control the inflammation. Sometimes this requires the use of immunosuppressants such as cyclosporin and methotrexate.

Alefacept is an immunosuppressant protein produced by genetic engineering. It binds to the CD2 receptor on T lymphocytes. This interferes with the lymphocyte activation which may contribute to the inflammation and proliferation of keratinocytes in psoriasis. Treatment with alefacept also reduces the lymphocyte count.

The recommended treatment regimen is 15 mg intramuscularly or 7.5 mg intravenously. Doses are given weekly for 12 weeks. Although there is limited information about the pharmacokinetics of alefacept, it has a half-life longer than ten days after intravenous injection.

A trial, using a range of intravenous doses, compared alefacept with placebo in 229 patients. As judged on the 0-72 scale of the psoriasis area and severity index, there were significant improvements in the patients given alefacept. Overall, 19 (11%) of the 170 patients randomised to take alefacept, but none of the placebo group, were clear of psoriasis at the end of the course of injections. Compared to their baseline measurements, 60% of the patients given 0.075 mg/kg had a 50% reduction in their psoriasis score.1

Another placebo-controlled trial investigated intramuscular alefacept (10 mg or 15 mg) in 507 patients with chronic plaque psoriasis. Twelve weeks of treatment resulted in 57% of the patients given 15 mg alefacept having a reduction of at least 50% in their psoriasis scores. The peak effect of the drug occurred after the course of injections was completed.2

Although the improvement in the patients' psoriasis can continue after treatment, some may benefit from a second course. A two course regimen was studied in a trial of 553 patients with chronic plaque psoriasis. These patients were randomised to receive two courses of intravenous alefacept 12 weeks apart, or a course of alefacept followed by placebo, or a course of placebo injections followed by alefacept. Two weeks after completion of the second course, 55% of the 183 patients who had received two courses of alefacept had a greater than 50% reduction in their psoriasis scores. Only 25% of the 142 who had received a placebo in their second course achieved the same outcome. The median duration of the response, in patients who responded well to their first course of alefacept, was more than seven months.3

Although symptoms such as chills and injection site reactions are common problems with alefacept, it has the potential for more serious adverse effects. Patients need their differential lymphocyte count checked every other week because of the risk of lymphopaenia. Alefacept should be withheld if the CD4 lymphocyte count is below normal.

The immunosuppressive effects of alefacept increase the risk of infections, particularly if the course is repeated. Some patients developed malignancies, such as lymphoma, during the clinical trials.

Psoriasis is a chronic disease, but the safety and efficacy of more than two courses of alefacept is unknown. While alefacept has a greater effect than placebo, up to 35% of patients will improve while taking a placebo. 2 As alefacept is likely to be expensive, it would be useful to know which patients will respond. Approximately nine patients need treatment to achieve clearance of one person's psoriasis. 1 Phototherapy and drugs such as topical corticosteroids were prohibited during the trials, so it would be interesting to know how these treatments compare with alefacept.

References

  1. Ellis CN, Krueger GG. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 2001;345:248-55.
  2. Lebwohl M, Christophers E, Langley R, Ortonne JP, Roberts J, Griffiths CE. An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch Dermatol 2003;139:719-27.
  3. Krueger GG, Papp KA, Stough DB, Loven KH, Gulliver WP, Ellis CN. A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis. J Am Acad Dermatol 2002;47:821-33.