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Abstract
Objective
Psoriasis and psoriatic arthritis (PsA) are thought of as T-cell mediated diseases.
LFA-3/CD2 interaction plays a significant role in T-cell activation. Alefacept, an
LFA3-IgG1 fusion protein, blocks LFA3-CD2 interactions resulting in inhibition of
T-cell responses and T-cell apoptosis which could be beneficial in patients with active
PsA.
Methods
Eleven patients with active PsA were treated with alefacept for 12 weeks in an open
label design. Clinical joint assessment, Psoriasis Area and Severity Index (PASI),
and peripheral blood (PB) assessments were performed at baseline, after 4,9,12, and
16 weeks of treatment. Serial synovial tissue (ST) biopsies of an index joint (knee,
ankle, wrist or MCP joint) were obtained by arthroscopy at baseline, 4 and 12 weeks.
Results
At completion of treatment 6 out of 11 (56%) treated patients fulfilled the DAS response
criteria, 9 patients (82%) fulfilled the DAS response criteria at any point within
the study. Seven of 11 (64%) treated patients showed improvement (mean 50%) of their
skin psoriasis. In the ST 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 synovial samples after 12 weeks of treatment compared to baseline. Patients
fulfilling the DAS response criteria demonstrated a higher baseline ration and significant
reduction in CD4+CD45RO+ cells in both ST and PB where non-responders demonstrated
only reductions in PB.
Conclusion
The improvement in clinical joint score, skin psoriasis, and changes in synovial tissue
after treatment with alefacept supports the hypothesis that T-cell activation plays
an important role in this chronic inflammatory disease. Furthermore, since alefacept,
a specific T-cell agent, led to decreased macrophage activation, the data indicate
that T cells orchestrate synovial inflammation in psoriatic arthritis.