title: An integrated analysis of thirteen trials summarizing the long-term safety of alefacept in psoriasis patients who have received up to nine courses of therapy.
abstract: BACKGROUND
  Information on longer-term safety and tolerability 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 > 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).
  
  
  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+ T lymphocyte counts. Fewer than 2.5% of patients tested positive for anti-alefacept antibodies during any course of therapy.
  
  
  CONCLUSIONS
  This integrated analysis of data from 13 trials with 1869 patients supports the safety and tolerability of alefacept for longer-term treatment of psoriasis.
authors.affiliation: Dermatolog Associates, Seattle, Washington 98101, USA. docgoffe@msn.com
authors.forename: Bernard
authors.initials: B
authors.lastname: Goffe
authors.forename: Kim
authors.initials: K
authors.lastname: Papp
authors.forename: David
authors.initials: D
authors.lastname: Gratton
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Krueger
authors.forename: Mohamed
authors.initials: M
authors.lastname: Darif
authors.forename: Sophia
authors.initials: S
authors.lastname: Lee
authors.forename: Carmen
authors.initials: C
authors.lastname: Bozic
authors.forename: Marianne T
authors.initials: MT
authors.lastname: Sweetser
authors.forename: Barry
authors.initials: B
authors.lastname: Ticho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077944:Alefacept; D000906:Antibodies / Q000032:analysis; D002986:Clinical Trials as Topic; D003879:Dermatologic Agents / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007239:Infections / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology; D011565:Psoriasis / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D003879:Dermatologic Agents; D011993:Recombinant Fusion Proteins; D000077944:Alefacept