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As expected, based on experience using alefacept in patients with chronic plaque psoriasis, onset of response was somewhat slow. Over time, however, the treatment was associated with clinical improvement in most patients without any serious safety concerns.
National report - As dermatologists continue to integrate biologics into their armamentarium for the treatment of patients with chronic plaque psoriasis, clinician-scientists are undertaking new studies to further explore how these agents may be used in the management of psoriasis.
In posters presented at the American Academy of Dermatology's Academy `05, groups of independent researchers presented their findings from phase 4, open-label studies evaluating alefacept (Amevive, Biogen) for the treatment of two forms of psoriasis that are particularly challenging - palmoplantar pustular disease and nail psoriasis.
The study evaluating alefacept for the treatment of palmoplantar pustular psoriasis (PPP) is a two-center pilot trial under way at Wake Forest University School of Medicine, Winston-Salem, N.C., and at the private practice of Dermatology Associates, Seattle. Principal investigators at those two sites are Steven R. Feldman, M.D., Ph.D., and Bernard Goffe, M.D., respectively.
"Palmoplantar psoriasis can have a devastating impact on quality of life because of its functional consequences, and it is often refractory to conventional treatments, including topical steroids, phototherapy and systemic agents," says Daniel Pearce, M.D., resident, department of dermatology, Wake Forest University School of Medicine. "Further study with longer follow-up is needed to better characterize the efficacy and safety of alefacept in the treatment of palmoplantar disease, but it appears, based on our preliminary analysis, that it can be considered as a valid option."
Palmoplantar pustular psoriasis
Subjects eligible for participation in the study were adults with PPP deemed by the investigator to require phototherapy or systemic therapy. Many patients had received previous therapies without sufficient response. Patients receiving oral methotrexate or acitretin were allowed to enter the alefacept study and could continue on those systemic medications if the dose had been stable for at least three months prior and was to be maintained constant during the trial.
By June 2005, the planned enrollment of 15 patients had been completed.
"Recruitment for this study went quickly, which speaks for the devastating impact of PPP and the need for more effective therapies that are safe for long-term administration," Dr. Pearce tells Dermatology Times.
Alefacept treatment was initiated at a dose of 15 mg/week by intramuscular (IM) injection, to be increased to 30 mg/week after eight weeks if there was not an appreciable response. All of the subjects in the interim analysis were switched to the higher dose.
At the time of the interim analysis, 11 of the 15 patients had completed 16 weeks of treatment. Six of these had completed an additional 12 weeks of follow-up. One patient was still receiving alefacept, and three had dropped out for various reasons, but none due to adverse events.
Responses were assessed using the palmoplantar psoriasis severity instrument and the physician's global assessment of psoriasis. Both measures showed a slow onset of effect, but generally substantial therapeutic benefits by the end of the treatment period with continued improvement during up to 12 weeks of additional follow-up.
"This pattern is consistent with the clinical experience with alefacept in patients with plaque psoriasis and suggests that there may be some benefit for extending the duration of treatment," Dr. Pearce says.
Safety assessments included monitoring for adverse events, including special attention to infections and measurement of CD4+ T cell counts. CD4+ T cell counts decreased as expected during treatment, but never declined below 250 cells/mm3 , and in no patient was treatment withheld because of a low CD4+ T cell count.
An option for nail disease
Dermatologists at the University of Alabama School of Medicine, Birmingham, Ala., undertook a prospective study evaluating alefacept for the treatment of nail psoriasis. Patients were eligible for enrollment if they were 19 to 85 years of age and had moderate to severe nail psoriasis and skin psoriasis that warranted treatment with systemic therapy. Persons who had received treatment of the target nail within the past 28 days were excluded.