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.
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.
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.
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.