CHICAGO — Assessing CD4 T cells at week 4 during the treatment of psoriasis with alefacept can reduce the need for further lymphocyte monitoring in some patients, Jennifer Cather, M.D., reported at the International Psoriasis Symposium sponsored by the Skin Disease Education Foundation.
The strategy could also lower costs and make alefacept therapy more convenient, she added.
Weekly CD4 counts are required by the alefacept (Amevive) package insert throughout the 12-week treatment regimen and are done as standard of care.
Dr. Cather suggested that the counts at week 4 can predict with a high degree of accuracy what the counts for weeks 5–12 will be.
If the count is more than 600 cells/μL at week 4, there is less than a 0.1% chance of having a subsequent CD4 count fall below 250 cells/μL, Dr. Cather said.
Therefore, she explained, weekly monitoring during the remaining treatment may be unnecessary in these patients.
Monitoring should be performed monthly for patients with a count between 400 cells/μL and 600 cells/μL, and every 2 weeks if the count is less than 400 cells/μL at week 4.
If a patient's CD4 count is less than 250 cells/μL at any time during alefacept treatment, the drug is usually withheld and testing should be done weekly until the count is 250 cells/μL or greater.
The recommendations are from a proposed monitoring algorithm based on a mathematical model and later confirmed at Baylor University Medical Center at Dallas, where Dr. Cather is codirector of the cutaneous lymphoma and graft vs. host disease clinic.
Biogen Idec, which makes alefacept, revised its package insert for the biologic last year after concerns were raised about serious liver injury in two patients. It is important to monitor for liver enzyme elevations in patients with psoriasis and psoriatic arthritis, said Dr. Cather, who has received funding support from Biogen Idec.
“I think that the hepatotoxicity that we see with a lot of these biologics is because the patient's liver is different,” she said. “Perhaps the increased hepatotoxicity is a result of increased body mass index and steatohepatitis.”
Ongoing trials are evaluating whether longer treatment with alefacept is needed to improve its efficacy, suggesting that long-term monitoring will remain important for physicians and patients.
Early data suggest that the addition of four doses to the 12-week treatment regimen increased response rates in patients with psoriasis, and that multiple courses may improve clinical responses in psoriasis patients who fail to show a strong initial response, she said.
“In addition, there are some data that show that their duration of remission in between each course improves with multiple courses,” said Dr. Cather.
In 197 patients with psoriasis who received 264 courses of alefacept at Baylor University independent of clinical trials, CD4 counts did not fall below 400 cells/μL in any of the patients, she said.
A total of 109 (41%) of treatments were 12-week courses of alefacept in combination with other therapies, including methotrexate, cyclosporine, hydroxyurea, ultraviolet B light, and acitretin. A total of 83 (32%) were standard 12-week alefacept monotherapy courses; 63 (24%) were extended courses of alefacept for 12 or more weeks either as monotherapy or in combination with other agents; and 8 (3%) were double-dose or alternative-dosing regimens.
The most common adverse events were fatigue, joint pain, aches, and chills.
There were five cases of infection, four malignancies including three skin cancers and one case of lung cancer, and no cases of liver or kidney toxicity.
Dr. Cather noted that in a recent case report of alefacept in two patients with hepatitis C infection and psoriasis, decreases in CD4 and CD8 counts were transient, and were not associated with either an increase in hepatitis viral loads or exacerbation of infection (Br. J. Dermatol. 2005;152:1048–50).
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