Subcutaneously administered efalizumab (anti-CD11a) improves signs and symptoms of moderate to severe plaque psoriasis.
BACKGROUND
Phase I and Phase II studies in patients with moderate to severe plaque psoriasis demonstrated that intravenous (IV) efalizumab improved clinical signs and symptoms and was well tolerated.


OBJECTIVE
To determine if subcutaneous (SC) delivery of efalizumab improves chronic plaque psoriasis and demonstrates an acceptable safety profile.


METHODS
This was a Phase I, open-label, single- and multiple-dose, escalating-dose study. Subjects received a single dose of efalizumab (0.3 mg/kg/wk SC) or escalating multiple doses of efalizumab (0.50-2.0 mg/kg/wk SC). Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI), target lesion assessment, and Physician's Global Assessment (PGA). Safety was assessed by evaluating adverse events, clinical laboratory test results, physical examination results, immunologic responses, and vital signs.


RESULTS
PASI score, target lesion assessment, and PGA showed improvement of approximately 40%-60% in signs and symptoms of plaque psoriasis by day 56. Mean PASI scores were still declining at the end of the eight-week dosing period, suggesting that longer duration of treatment would be more effective. By day 91, mean PASI scores were 16.2 vs. 14.6 at day 56 in the 0.5-1.0-mg/kg/wk group and 11.7 vs. 10.1 in the 1.0-2.0-mg/kg/wk group. This demonstrates that, on average, patients maintained their treatment benefit during the 42-day followup period. Overall, there were considerably fewer adverse events than in previous IV studies. These consisted principally of mild to moderate headache, pain, and rhinitis. No allergic reactions were observed. Antibodies to efalizumab were observed in only one subject (2%) and did not have any clinical relevance.


CONCLUSIONS
The SC administration of eight weekly doses of efalizumab improves signs and symptoms of psoriasis. The treatment was safe and very well tolerated. In comparison to previously published results with IV efalizumab, SC administration of efalizumab improves overall safety and tolerability, with the additional advantage of greater convenience.
Gottlieb
Alice B
AB
Clinical Research Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903-0019, USA. gottliab@UMDNJ.EDU
Miller
Bruce
B
Lowe
Nicholas
N
Shapiro
William
W
Hudson
Charles
C
Bright
Ross
R
Ling
Mark
M
Magee
Anna
A
McCall
Calvin O
CO
Rist
Toivo
T
Dummer
Wolfgang
W
Walicke
Patricia
P
Bauer
Robert J
RJ
White
Mark
M
Garovoy
Marvin
M
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens; C472181:efalizumab