Alefacept treatment in psoriatic arthritis: reduction of the synovial inflammatory infiltrate and improvement of clinical signs of arthritis

  • MC Kraan1,

    Affiliated with

    • HJ Dinant1,

      Affiliated with

      • AWR van Kuijk2,

        Affiliated with

        • AY Goedkoop1,

          Affiliated with

          • TJM Smeets1,

            Affiliated with

            • MA de Rie1,

              Affiliated with

              • BAC Dijkmans2,

                Affiliated with

                • AK Vaishnaw3 and

                  Affiliated with

                  • PP Tak1

                    Affiliated with

                    Arthritis Res20024(Suppl 1):101

                    DOI: 10.1186/ar436

                    Received: 15 January 2002

                    Published: 4 February 2002

                    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.

                    Authors’ Affiliations

                    (1)
                    Academic Medical Center
                    (2)
                    Acad Hospital Free University
                    (3)
                    Biogen Inc

                    Copyright

                    © BioMed Central Ltd 2002

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