Biomedical subjects

Alefacept Clinical Study Group

Publications and source records attributed to Alefacept Clinical Study Group.

6 recordsLinked to original sources

PubMed2003

Treatment of psoriasis with alefacept: correlation of clinical improvement with reductions of memory T-cell counts.

OBJECTIVE: To examine the relationship between the pharmacodynamic and antipsoriatic effects of alefacept, a biologic agent that targets CD4+ and CD8+ memory T cells. DESIGN: Randomized, double-blind, placebo-controlled study of 3 parallel groups. SETTING: Fifty-one study centers. PATIENTS: Five hundred fifty-three patients with chronic plaque psoriasis. INTERVENTIONS: Patients were randomized (1:1:1) to 1 of the following 3 cohorts: alefacept, 7.5 mg, in both courses (cohort 1); alefacept, 7.5 mg, in the first course and placebo in the second course (cohort 2); or placebo in the first course and alefacept, 7.5 mg, in the second course (cohort 3). In each course, alefacept or placebo was administered by intravenous bolus once weekly for 12 weeks, followed by 12 weeks of observation. MAIN OUTCOME MEASURES: Circulating lymphocyte levels and the Psoriasis Area Severity Index. RESULTS: One or 2 courses of alefacept reduced CD4+ and CD8+ memory T-cell counts, while sparing the naive population. At 12 weeks after the last dose of alefacept in courses 1 and 2, 88% and 83% of patients, respectively, had CD4+ cell counts greater than the lower limit of normal. In course 1, alefacept-treated patients with the largest decreases in memory T-cell counts experienced the greatest reductions in disease activity (P<.001). The duration of clinical benefit seemed to be longer among patients who had the greatest reduction in CD4+ and CD8+ memory T-cell counts. CONCLUSIONS: One or 2 courses of intravenous alefacept reduced circulating memory T-cell counts while sparing the naïve T-cell population. The reductions in memory T-cell counts were related to all measures of disease activity evaluated and the duration of response to therapy, suggesting that prolonged remissions of psoriasis can be attained with reduction of the pathogenic T-cell count.

Adolescent↗

PubMed2003

An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis.

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. CONCLUSION: Intramuscular administration of alefacept was a well-tolerated and effective therapy for chronic plaque psoriasis and thus represents a convenient alternative to intravenous dosing.

Adolescent↗

PubMed2003

Intramuscular alefacept improves health-related quality of life in patients with chronic plaque psoriasis.

BACKGROUND: Psoriasis profoundly affects patient quality of life (QOL). Amevive (alefacept), a novel and selective biologic agent, was clinically effective and significantly improved QOL in a phase 2 study. METHODS: The present placebo-controlled, randomized phase 3 study examined the effects of a 12-week course of intramuscular alefacept on QOL in 507 patients with chronic plaque psoriasis using both dermatology-specific questionnaires [Dermatology Life Quality Index (DLQI); Dermatology Quality of Life Scales (DQOLS)] and the Short Form-36 Health Survey (SF-36), a generic, general health questionnaire. RESULTS: All 3 QOL measures (DLQI, DQOLS, SF-36) demonstrated that alefacept 15 mg was significantly more effective than placebo in improving QOL in patients with chronic plaque psoriasis. In addition, the improvements in QOL for patients in the alefacept 15 mg group were of similar magnitude for all 3 QOL measures. CONCLUSION: The findings of this study are an important addition to the QOL literature for psoriasis treatments.

Alefacept↗

PubMed2002

A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis.

BACKGROUND: In previous phase II studies, alefacept significantly improved psoriasis and was well tolerated. The clinical response to alefacept was durable. OBJECTIVE: Our purpose was to further evaluate efficacy and tolerability of alefacept in a phase III study of patients (n = 553) with chronic plaque psoriasis. METHODS: Two 12-week courses of once-weekly intravenous alefacept 7.5 mg or placebo were given in a randomized double-blind study; patients were followed up for 12 weeks after each course. RESULTS: During treatment and follow-up of course 1, a 75% or greater reduction in the Psoriasis Area Severity Index (PASI) was achieved by 28% of alefacept-treated and 8% of placebo-treated patients (P <.001). Patients who received a single course of alefacept and achieved a 75% or greater reduction from baseline PASI during or after treatment, without the use of phototherapy or systemic therapies, maintained a 50% or greater reduction in PASI for a median duration of more than 7 months. Among patients who received 2 courses of alefacept, 40% and 71% of patients achieved a 75% or greater and 50% or greater reduction in PASI, respectively, during the study period. Alefacept was well tolerated over both courses. In course 1, the incidence of transient chills was higher in the alefacept group compared with the placebo group; more than 90% of cases occurred within 24 hours after the first few doses. CONCLUSION: Alefacept significantly improved psoriasis and produced durable clinical improvements among patients who responded. A second course of alefacept increased efficacy and was equally well tolerated.

Adolescent↗

PubMed2001

Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes.

BACKGROUND: Psoriatic plaques are characterized by infiltration with CD4+ CD45RO+ and CD8+ CD45RO+ memory effector T lymphocytes. The recombinant protein alefacept binds to CD2 on memory effector T lymphocytes, inhibiting their activation. METHODS: In a multicenter, randomized, placebo-controlled, double-blind study, we evaluated alefacept as a treatment for psoriasis. Two hundred twenty-nine patients with chronic psoriasis received intravenous alefacept (0.025, 0.075, or 0.150 mg per kilogram of body weight) or placebo weekly for 12 weeks, with follow-up for 12 additional weeks. Before treatment, the median scores on the psoriasis area-and-severity index were between 14 and 20 in all groups (0 denotes no psoriasis and 72 the most severe disease possible). RESULTS: Alefacept was well tolerated and nonimmunogenic. The mean reduction in the score on the psoriasis area-and-severity index two weeks after treatment was greater in the alefacept groups (38, 53, and 53 percent in the groups receiving 0.025, 0.075, and 0.150 mg per kilogram, respectively) than in the placebo group (21 percent, P<0.001). Twelve weeks after treatment, 28 patients who had received alefacept alone were clear or almost clear of psoriasis. Three patients in the placebo group were clear or almost clear; all three had received additional systemic therapy for psoriasis. Alefacept reduced peripheral-blood memory effector T-lymphocyte (CD45RO+) counts, and the reduction in the number of memory-effector T lymphocytes was correlated with the improvement in psoriasis. CONCLUSIONS: Treatment with alefacept for 12 weeks is associated with improvement in chronic plaque psoriasis; some patients have a sustained clinical response after the cessation of treatment. Alefacept selectively targets CD45RO+ memory effector T lymphocytes, suggesting that they have a role in the pathogenesis of psoriasis.

Adjuvants, Immunologic↗

PubMedDate not supplied

Alefacept-induced decreases in circulating blood lymphocyte counts correlate with clinical response in patients with chronic plaque psoriasis.

This international, double-blind study examined the effects of alefacept on circulating lymphocytes in 507 patients with chronic plaque psoriasis, and determined whether these effects were related to clinical improvement. Patients were randomized to intramuscular placebo, alefacept 10 mg, or alefacept 15 mg once weekly for 12 weeks followed by 12 weeks of observation. Alefacept dose-dependently reduced CD4+ and CD8+ memory T cells, while sparing the na ve population. The greatest reductions in disease activity occurred in patients with the largest decreases in memory T cells. For example, a 50 % reduction from baseline Psoriasis Area Severity Index at any time during treatment or follow-up was observed in 66 % of patients who had the greatest reductions in CD4+ memory T cells versus in 40 % of patients who had the smallest reductions in this T-cell subset. These results provide further support for the deleterious roles of CD4+ and CD8+ memory T-cell subpopulations in psoriasis pathogenesis.

Alefacept↗