Clinical update on alefacept: consideration for use in patients with psoriasis.
OBJECTIVE
Alefacept was the first of the biologic agents to be approved for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. This fully human fusion protein inhibits the activation of and reduces levels of memory (CD45RO+) T cells, a subpopulation of lymphocytes that plays a critical role in the pathogenesis of psoriasis. The purpose of this article is to provide a clinical update on the use of this agent in patients with psoriasis.


CONCLUSIONS
A single course of alefacept, defined as 12 weekly injections followed by 12 treatment-free weeks, provides clinically meaningful improvements in the symptoms of psoriasis for a majority of patients. Patients who achieved a response have been shown to maintain the benefit for a median duration of about 7 months, without the need for systemic therapy or phototherapy. With each additional course of alefacept, the percentage of patients responding increases, confirming the incremental benefit of repeated administration. More than 1,300 patients have received alefacept in controlled clinical trials. Over multiple courses of therapy, alefacept-induced reductions in circulating lymphocyte counts were consistent and not cumulative. The incidences of serious adverse events, discontinuations, malignancies, and antialefacept antibodies were low and did not increase with subsequent courses. No relationship was observed between decreases in lymphocyte counts and incidences of infections or malignancies. No cases of opportunistic infections, including tuberculosis, have been reported. The favorable safety profile of alefacept was maintained in patients who received concomitant or prior immunosuppressants. Alefacept did not cause reactivation of tuberculosis in case studies of patients who showed a purified protein derivative reaction prior to the initiation of therapy. Immune responses to a neoantigen and recall antigen remained intact in alefacept-treated patients, suggesting that vaccinations may be possible during therapy.


CONCLUSIONS
Alefacept is an effective intermittent therapy for psoriasis that can provide extended treatment-free and disease-free periods, which may lessen the need for treatment over time. The incremental efficacy seen with each subsequent course of alefacept suggests that physicians should administer 2 courses to determine efficacy before altering therapeutic interventions. The selective mechanism of action of alefacept affords multiple safety advantages and no apparent increased risk of infections or malignancies.
Gade
Jay N
JN
Dermatology and Laser Center of Roseburg, Oregon 97470, USA. roseburgderm@cmspan.net
D000077944:Alefacept; D001691:Biological Therapy; D006801:Humans; D007267:Injections; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects; D016896:Treatment Outcome
D011993:Recombinant Fusion Proteins; D000077944:Alefacept