-
New England Journal of Medicine 04/2013; 368(17):1659-61. · 53.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Alefacept selectively reduces memory T cells and inhibits T-cell activation. Large randomized trials have shown that intramuscular (IM) delivery of alefacept is safe and effective in treating plaque psoriasis. Subcutaneous (SC) administration of alefacept may provide advantages for some patients including convenience, ease of use, and reduced pain on injection. We conducted a randomized, open-label, crossover study in 50 healthy volunteers to determine if alefacept 15 mg administered SC is bioequivalent to alefacept 15 mg administered IM. The pharmacokinetic parameters used to determine bioequivalence were area under the serum concentration-time curve to the last measurable value (AUClast; primary endpoint), peak serum concentration (Cmax), and AUC to infinity (AUCinfinity). For each of these parameters, the 90 percent confidence intervals for the least squares mean ratios of alefacept SC to alefacept IM were well within the conventional bioequivalence range of 80 percent to 125 percent. These data, together with the finding that the mean serum concentration-time curves for alefacept were nearly identical following both routes of administration, demonstrate the bioequivalence of alefacept SC and alefacept IM. No clinically important differences between the pharmacodynamic profiles (total lymphocyte and lymphocyte subset counts) of the two routes of administration were observed. Alefacept SC and alefacept IM were similarly well tolerated. Our results suggest that SC dosing may represent a viable delivery option for alefacept.
Dermatology online journal 02/2006; 12(3):1.
-
[show abstract]
[hide abstract]
ABSTRACT: Information on longer-term safety and tolerability is needed to confidently prescribe alefacept therapy for chronic plaque psoriasis beyond 1 or 2 courses.
The aim of this work was to further examine the safety profile of alefacept by integrating data from clinical trials involving patients with chronic plaque psoriasis who received up to 9 courses of therapy over a 5-year period.
Data from 13 clinical trials conducted in patients with plaque psoriasis were integrated because they had similar inclusion/exclusion criteria and assessments. Patients who enrolled in the analyzed trials were aged > or =15 years with chronic plaque psoriasis for > or =12 months that involved > or =10% of body surface area, and CD4+ T lymphocyte counts above the lower limit of normal (>404 cells/microL). The incidences of adverse events (AEs), serious AEs, discontinuations for AEs, infections, serious infections, malignancies, and anti-alefacept antibodies were summarized for each course of alefacept. The incidence of infections was stratified according to CD4+ T lymphocyte counts (<250 cells/microL vs > or =250 cells/microL).
Data from 13 clinical trials of alefacept were integrated and summarized (multicenter, randomized, double-blind studies, n = 6; multicenter, open-label studies, n = 5; other, n = 2). The analyzed population (n = 1869) included 1291 (69.1%) men and 578 (30.9%) women, between the ages of 15 and 84 years (mean, 44.8 years), of whom 1648 (88.2%) were white. Weights ranged from 40 kg to 206 kg (mean, 90.0 kg). A total of 1369 of these patients had been included in a previous analysis. Among the most commonly reported AEs in each treatment course were headache (0%-14.2%), nasopharyngitis (7.7%-25.0%), influenza (0%-8.1%), upper respiratory tract infection (0%-12.5%), and pruritus (0%-7.5%). The rates of discontinuations due to AEs (0%-4.8%), serious AEs (0%-4.8%), serious infections (0%-0.9%), or malignancies (0%-4.8%) did not appear to increase with repeated exposure. Fewer than 1 % of patients in each course developed a serious infection. No opportunistic infections or infection-related deaths were reported. The incidence of infections appeared to be unrelated to CD4+ T lymphocyte counts. Fewer than 2.5% of patients tested positive for anti-alefacept antibodies during any course of therapy.
This integrated analysis of data from 13 trials with 1869 patients supports the safety and tolerability of alefacept for longer-term treatment of psoriasis.
Clinical Therapeutics 01/2006; 27(12):1912-21. · 2.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Combination therapy for moderate to severe psoriasis is often used to enhance efficacy and minimize treatment-related side effects; however, data are limited on combination therapy with the newer biologic agents. The current study examined patients who received alefacept in combination with ultraviolet B phototherapy as part of an international, open-label study evaluating up to 3 courses of alefacept in combination with other psoriasis therapies. Physician Global Assessment [corrected] scores improved by [greater than or equal to] 1 category in 88% [corrected] of patients and by [greater than or equal to] 2 categories in 76% [corrected] of patients in course A; [corrected] corresponding response rates were 100% and 55% in Course [corrected] B, and 85% and 77% in Course [corrected] C. At week 14, a PGA of "almost clear" or "clear" was achieved by 13%, 14%, and 8% of patients in courses A, B, and C, respectively. There was no evidence of a cumulative effect on T cells after multiple courses of therapy. The combination of alefacept and ultraviolet B was well tolerated and provided improvement in psoriasis.
Journal of drugs in dermatology: JDD 5(7):623-8. · 1.57 Impact Factor
