Alefacept treatment in psoriatic arthritis: reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis.
OBJECTIVE
To investigate whether alefacept (a fully human lymphocyte function-associated antigen 3 [LFA-3]/IgG1 fusion protein that blocks the LFA-3/CD2 interaction) is able to reduce the signs and symptoms of joint inflammation in patients with active psoriatic arthritis (PsA).


METHODS
Eleven patients with active PsA were treated with alefacept for 12 weeks in an open-label and explorative study. Clinical joint assessment and laboratory assessments were performed at baseline and after 4, 9, 12, and 16 weeks of treatment. Serial synovial tissue (ST) biopsy specimens from an inflamed index joint (knee, ankle, wrist, or metacarpophalangeal joint) were obtained by arthroscopy at baseline and after 4 and 12 weeks of treatment.


RESULTS
At the completion of treatment, 6 of 11 patients (55%) fulfilled the Disease Activity Score (DAS) response criteria. Nine patients (82%) fulfilled the DAS response criteria at any point during the study. There was a statistically significant reduction in CD4+ lymphocytes (P < 0.05), CD8+ lymphocytes (P = 0.05), and CD68+ macrophages (P < 0.02) in the ST after 12 weeks of treatment compared with baseline. The ST and peripheral blood of those patients fulfilling the DAS response criteria contained more CD45RO+ cells at baseline and displayed a significant reduction in these cells compared with nonresponding patients.


CONCLUSIONS
The changes in ST, together with the improvement in clinical joint scores, after treatment with alefacept support the hypothesis that T cell activation plays an important role in this chronic inflammatory disease. Furthermore, since alefacept, a T cell-specific agent, led to decreased macrophage infiltration, the data indicate that T cells are highly involved in synovial inflammation in PsA.
Kraan
Maarten C
MC
Division of Clinical Immunology and Rheumatology F4-218, Academic Medical Center/University of Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands. m.c.kraan@amc.uva.nl
van Kuijk
Arno W R
AW
Dinant
Huibert J
HJ
Goedkoop
Amber Y
AY
Smeets
Tom J M
TJ
de Rie
Menno A
MA
Dijkmans
Ben A C
BA
Vaishnaw
Akshay K
AK
Bos
Jan D
JD
Tak
Paul P
PP
D000328:Adult; D000368:Aged; D000077944:Alefacept; D015535:Arthritis, Psoriatic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001182:Arthroscopy; D015704:CD4 Antigens / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000032:analysis; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
D015704:CD4 Antigens; D011993:Recombinant Fusion Proteins; D017493:Leukocyte Common Antigens; D000077944:Alefacept