Elsevier

Clinical Therapeutics

Volume 27, Issue 12, December 2005, Pages 1912-1921
Clinical Therapeutics

Original research
An integrated analysis of thirteen trials summarizing thelong-term safety of alefacept in psoriasis patients who have received up to nine courses of therapy*

https://doi.org/10.1016/j.clinthera.2005.12.007Get rights and content

Abstract

Background:

Information on longer-term safety andtolerability is needed to confidently prescribe alefacept therapy for chronic plaque psoriasis beyond 1 or 2 courses.

Objective:

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.

Methods:

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 ≥15 years with chronic plaque psoriasis for ≥12 months that involved ≥10% of body surface area, and CD4+ Tlymphocyte counts above the lower limit of normal (>404 cells/μL). 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+ Tlymphocyte counts (<250 cells/μL vs ≥250 cells/μL).

Results:

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+ Tlymphocyte counts. Fewer than 2.5% of patients tested positive for anti-alefacept antibodies during any course of therapy.

Conclusions:

This integrated analysis of data from13 trials with 1869 patients supports the safety and tolerability of alefacept for longer-term treatment of psoriasis.

References (25)

  • LebwohlM. et al.

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

    Arch Dermatol

    (2003)
  • FinlayA.Y. et al.

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

    Dermatology

    (2003)
  • Cited by (65)

    • Correlation among Hypoglycemia, Glycemic Variability, and C-Peptide Preservation after Alefacept Therapy in Patients with Type 1 Diabetes Mellitus: Analysis of Data from the Immune Tolerance Network T1DAL Trial

      2016, Clinical Therapeutics
      Citation Excerpt :

      Maintenance of islet preservation for extended periods may require additional courses of treatment. In psoriasis, up to 9 courses of alefacept therapy have been given during a 5-year period with no evidence of increased toxic effects with repeated exposure.47 Moreover, recent studies suggest it may be possible to lengthen the interval between doses of biologics in psoriasis,48 which could also be considered during the further development of alefacept for the treatment of T1D.

    • Immune Compromise Associated with Biologics

      2014, Stiehm's Immune Deficiencies
    • Biologic systemic therapy for moderate-to-severe psoriasis: A review

      2013, Journal of Taibah University Medical Sciences
      Citation Excerpt :

      Given infliximab’s characteristic rapid onset of action and high response rates, it is recommended when rapid disease control is required in unstable conditions such as erythrodermic or pustular psoriasis.44 The recommended dosing regimen for infliximab is a 5 mg/kg IV infusion, to be repeated at 2, 6, and then every 8 weeks thereafter.65 Clinical effect can be expected in 1–2 weeks.57

    View all citing articles on Scopus
    *

    This work was presented in part at the International Psoriasis Symposium, June 9–13, 2004, Montreal, Quebec, Canada; the Academy of Managed Care Pharmacy Fall Educational Conference, October 13–16, 2004, Baltimore, Maryland; the 63rd Annual Meeting of the American Academy of Dermatology, February 18–22, 2005, New Orleans, Louisiana; the Australasian College of Dermatologists Meeting, May 15–18, 2005, Perth, Australia; and the 80th Annual Conference of the Canadian Dermatology Association, June 28 July 3, 2005, Quebec City, Quebec, Canada.

    View full text