PMID- 16507377
OWN - NLM
STAT- MEDLINE
DCOM- 20060411
LR  - 20191210
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 27
IP  - 12
DP  - 2005 Dec
TI  - 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.
PG  - 1912-21
AB  - 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.
FAU - Goffe, Bernard
AU  - Goffe B
AD  - Dermatolog Associates, Seattle, Washington 98101, USA. docgoffe@msn.com
FAU - Papp, Kim
AU  - Papp K
FAU - Gratton, David
AU  - Gratton D
FAU - Krueger, Gerald G
AU  - Krueger GG
FAU - Darif, Mohamed
AU  - Darif M
FAU - Lee, Sophia
AU  - Lee S
FAU - Bozic, Carmen
AU  - Bozic C
FAU - Sweetser, Marianne T
AU  - Sweetser MT
FAU - Ticho, Barry
AU  - Ticho B
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antibodies)
RN  - 0 (Dermatologic Agents)
RN  - 0 (Recombinant Fusion Proteins)
RN  - ELK3V90G6C (Alefacept)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alefacept
MH  - Antibodies/analysis
MH  - Clinical Trials as Topic
MH  - Dermatologic Agents/immunology/*therapeutic use
MH  - Female
MH  - Humans
MH  - Infections/epidemiology
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/epidemiology
MH  - Psoriasis/*drug therapy
MH  - Recombinant Fusion Proteins/immunology/*therapeutic use
EDAT- 2006/03/02 09:00
MHDA- 2006/04/12 09:00
CRDT- 2006/03/02 09:00
PHST- 2005/10/18 00:00 [accepted]
PHST- 2006/03/02 09:00 [pubmed]
PHST- 2006/04/12 09:00 [medline]
PHST- 2006/03/02 09:00 [entrez]
AID - S0149-2918(05)00319-X [pii]
AID - 10.1016/j.clinthera.2005.12.007 [doi]
PST - ppublish
SO  - Clin Ther. 2005 Dec;27(12):1912-21. doi: 10.1016/j.clinthera.2005.12.007.