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Psoriasis treatment with drugs designed to block T-cell activation
associated with the autoimmune disease continues to show promise in several
clinical studies. The success of this psoriasis treatment, with few side-
effects, holds great hope and promise for the development of similar drugs
to block T-cell activation in celiac disease.
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Medscape Medical News
Release Date: June 23, 2003
Alefacept Effective, Well Tolerated for Plaque Psoriasis
News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD
You must be registered with Medscape (free) to read this article:
http://www.medscape.com/viewarticle/457631
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Arch Dermatol. 2003 Jun;139(6):719-27.
An International, Randomized, Double-blind, Placebo-Controlled Phase 3
Trial of Intramuscular Alefacept in Patients With Chronic Plaque Psoriasis.
Lebwohl M, Christophers E, Langley R, Ortonne JP, Roberts J, Griffiths CE.
Mount Sinai School of Medicine, New York, NY.
BACKGROUND: Alefacept, human lymphocyte function-associated antigen
3/immunoglobulin 1 fusion protein, binds to CD2 molecules on the surface of
activated T cells, selectively targeting memory-effector (CD45RO+) T cells,
which comprise more than 75% of T cells in psoriatic plaques. OBJECTIVE: To
examine the efficacy and tolerability of intramuscular alefacept. DESIGN:
International, randomized, double-blind, placebo-controlled, parallel-group
trial.Patients A total of 507 patients with chronic plaque
psoriasis.Intervention Placebo, 10 mg of alefacept, or 15 mg of alefacept
administered once weekly for 12 weeks followed by 12 weeks of
observation.Main Outcome Measure Psoriasis Area Severity Index (PASI).
RESULTS: Alefacept treatment was associated with dose-related significant
improvements in PASI from baseline. Throughout the study, a greater
percentage of patients in the 15-mg group than in the placebo group
achieved a significant reduction in PASI. Of patients in the 15-mg group
who achieved at least 75% PASI reduction 2 weeks after the last dose, 71%
maintained at least 50% improvement in PASI throughout the 12-week follow-
up. There were no opportunistic infections and no cases of disease
rebound. CONCLUSIONS: Intramuscular administration of alefacept was a well-
tolerated and effective therapy for chronic plaque psoriasis and thus
represents a convenient alternative to intravenous dosing.
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J Eur Acad Dermatol Venereol. 2003 Jul;17 Suppl 2:17-24.
Clinical response to alefacept: results of a phase 3 study of intravenous
administration of alefacept in patients with chronic plaque psoriasis.
Krueger G.
Department of Dermatology, University of Utah School of Medicine, Salt Lake
City, Utah, USA, E-mail: [log in to unmask]
BACKGROUND: There is a current lack of safe and effective psoriasis
therapies that provide patients with lasting remissions after treatment is
discontinued. Alefacept, a novel and selective biological agent, has
demonstrated durable efficacy in patients with chronic plaque psoriasis,
and its efficacy has been correlated with reductions in memory-effector T
cells. OBJECTIVE: To demonstrate the efficacy and safety of both one and
two 12-week courses of alefacept 7.5 mg given once weekly as an intravenous
(IV) bolus injection in patients with chronic plaque psoriasis. METHODS:
Multicentre (51 centres in the USA and Canada), randomized, double-blind,
parallel-group study comparing once-weekly alefacept 7.5 mg IV or placebo
for two 12-week treatment courses. Each course had a 12-week follow-up
phase. Patients were eligible for enrolment if they were >/=16 years of
age, had chronic plaque psoriasis for >/=12 months involving >/=10% body
surface area, and had CD4+ T-cell counts at or above the lower limit of
normal. RESULTS: 553 patients received treatment in Course 1, and 449 were
treated in Course 2. The cohorts were well balanced for demographic and
baseline disease characteristics. During the treatment and follow-up period
of Course 1, 28% of patients treated with alefacept achieved >/=75%
reduction in Psoriasis Area and Severity Index (PASI), compared with 8% of
placebo-treated patients (P < 0.001). Patients achieving >/=75% reduction
in PASI following a single 12-week course of alefacept maintained >/=50%
reduction in PASI for a median of over 7 months. Among patients who
received a second course of alefacept therapy, 71% achieved >/=50%
reduction in PASI, and 40% achieved >/=75% reduction in PASI over two
treatment courses. One or two 12-week courses of alefacept were similarly
well tolerated. CONCLUSIONS: Treatment with alefacept 7.5 mg IV provided
highly significant improvements in all measures of psoriasis disease
activity compared with placebo. A second course of alefacept provided
additional benefit.
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J Eur Acad Dermatol Venereol. 2003 Jul;17 Suppl 2:12-6.
Clinical response to alefacept: results of a phase 3 study of intramuscular
administration of alefacept in patients with chronic plaque psoriasis.
Ortonne JP.
Department of Dermatology, University of Nice-Sophia Antipolis, Nice,
France, E-mail: [log in to unmask]
BACKGROUND: Recognition of psoriasis as a T-cell-mediated immune disease
has led to the development of various therapeutic approaches directed
against the pathogenic T cells. Alefacept, a novel and selective biological
recombinant protein, binds CD2 on T cells to block T-cell activation and
proliferation and interacts with FcgammaRIII receptors on accessory cells
to produce selective T-cell apoptosis. OBJECTIVE: To demonstrate the
efficacy and safety of once-weekly alefacept IM compared with placebo given
for 12 weeks to patients with chronic plaque psoriasis. METHODS:
Multicentre (63 sites in Europe, the USA, and Canada), randomized, double-
blind, parallel-group study comparing 10 mg and 15 mg of alefacept and
placebo administered IM once weekly for 12 weeks. Patients were followed
for an additional 12 weeks after cessation of therapy. Patients were
eligible for enrolment if they were >/= 18 years of age, had chronic plaque
psoriasis for >/= 12 months involving >/= 10% body surface area, and had
CD4+ T-cell counts at or above the lower limit of normal. RESULTS: 507
patients were enrolled into three treatment groups, which were well
balanced for demographic, baseline disease characteristics, and treatment
history. A significantly greater percentage of patients treated with
alefacept 15 mg IM achieved >/= 75% PASI reduction from baseline 2 weeks
after the last dose compared with placebo (21% vs. 5%, P < 0.001); 12% of
patients treated with alefacept 10 mg IM reached this level of improvement
(P = NS vs. placebo). Alefacept was well tolerated, with adverse events
similar to that of placebo. CONCLUSIONS: Treatment with alefacept 15 mg IM
provided highly significant improvements in all measures of psoriasis
disease activity compared with placebo. Pharmacodynamic data confirmed that
alefacept is a selective biological agent that reduces memory-effector T
cells (CD4+CD45RO+ and CD8+CD45RO+), the source of the pathogenic mediators
of psoriasis, while having relatively no effect on naive T-cell populations.
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J Eur Acad Dermatol Venereol. 2003 Jul;17 Suppl 2:6-11.
Targeting T-cell subsets to achieve remission.
Christophers E.
Department of Dermatology, University of Kiel, Kiel, Germany, Tel. +49
431597 1500; Fax +49 431597 1503; E-mail: [log in to unmask]
Patients with psoriasis have an increase in pathogenic CD45RO+ memory-
effector T cells during active disease. The genetically engineered fully
human fusion protein alefacept has been developed to selectively target
this subset of T cells. Alefacept binds to memory-effector CD45RO+ T cells,
inhibiting their activation and inducing T-cell apoptosis. The selectivity
of alefacept for memory-effector CD45RO+ T cells was evaluated in 229
patients with chronic psoriasis in a randomized, placebo-controlled, double-
blind study conducted at 22 centres in the USA. Patients received alefacept
intravenously at doses of 0.025 mg/kg, 0.075 mg/kg, or 0.150 mg/kg, or
placebo once weekly for 12 weeks. Two weeks after completing treatment,
patients receiving alefacept showed significant improvement in the
Psoriasis Area and Severity Index (PASI) compared with those receiving
placebo. Mean reductions in the PASI score were up to 53% lower than
baseline scores in the alefacept treatment group, compared with a 21%
decline from baseline in the placebo group (P < 0.001). In addition to the
significant improvement in psoriasis, treatment with alefacept produced
long-term remission in some patients. Twelve weeks after completion of
therapy, 28 patients became clear or almost clear. The therapy was well
tolerated and nonimmunogenic. Importantly, during treatment, there was a
correlation between improvement in psoriasis and a dose-dependent reduction
in peripheral blood CD45RO+ memory-effector T cells, but not in CD45RA+
naive T cells. This correlation indicates a relationship between a specific
T-cell subset reduction (CD45RO+) and clinical outcome in psoriasis.
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