Open-label, single-center, safety dose escalation trial of alefacept for the treatment of moderate to severe chronic plaque psoriasis.
BACKGROUND
Alefacept (Amevive) is a fully human LFA-3/IgG1 fusion protein with a dual mechanism of action inhibiting T-cell activation and selectively reducing memory T cells. Alefacept is currently approved as a 12-week course of weekly 15 mg intramuscular (IM) injections for the treatment of adults with moderate to severe chronic plaque psoriasis. In clinical trials using the currently approved dosing regimen, 33% and 57% of patients achieved a 75% or greater or 50% or greater reduction in Psoriasis Area and Severity Index score (PASI 75 and PASI 50), respectively, after one course of alefacept.


OBJECTIVE
To evaluate the tolerability and efficacy of alefacept 15 mg IM weekly for 6 weeks followed by alefacept 30 mg IM weekly for 6 weeks.


METHODS
Open-label, single-center, dose escalation study of alefacept.


METHODS
Adult patients with chronic plaque psoriasis involving a minimum body surface area of 10% and with a minimum PASI of 12.


METHODS
Patients were treated with alefacept 15 mg IM for 6 weeks followed by alefacept 30 mg IM for an additional 6 weeks; doses were held for CD4 counts < 200 cells/mm(3) or evidence of a clinically significant infection.


METHODS
Efficacy was evaluated by PASI and Physician Global Assessment (PGA) at baseline, week 7, and 2, 6, 12, and 24 weeks post-treatment.


RESULTS
Sixteen patients were enrolled; at 6 weeks post-treatment, the PASI mean reduction was 39%, with continued improvement to 46% at 12 weeks post-treatment. The PASI 90, PASI 75, and PASI 50 responses at 12 weeks post-treatment were 6% (1 of 16), 13% (2 of 16), and 38% (6 of 16), respectively; 12% (2 of 16) of patients achieved a PGA of clear to almost clear at 12 weeks post-treatment. The overall PASI 75 and PASI 50 responses were 19% (3 of 16) and 38% (6 of 16), respectively.


CONCLUSIONS
The treatment regimen of alefacept 15 mg IM for 6 weeks followed by alefacept 30 mg IM for 6 weeks was well tolerated by our patients. There was no increased incidence of infections when patients were treated with alefacept 30 mg compared with the 15 mg dose. The increased dose of alefacept 30 mg for the last 6 weeks of a 12-week course did not appear to yield a higher efficacy rate compared with historical controls.
Moul
Danielle K
DK
University Hospitals of Cleveland, Case Medical Center, Cleveland, OH 44106, USA.
Routhouska
Shannon B
SB
Korman
Neil J
NJ
D000328:Adult; D000077944:Alefacept; D002908:Chronic Disease; D003879:Dermatologic Agents / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D012449:Safety; D012720:Severity of Illness Index
D003879:Dermatologic Agents; D011993:Recombinant Fusion Proteins; D000077944:Alefacept