TY - JOUR T1 - Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial. JF - The Journal of Rheumatology JO - J Rheumatol SP - 1907 LP - 1913 VL - 29 IS - 9 AU - Tammy O Utset AU - Julie A Auger AU - Donna Peace AU - Robert A Zivin AU - Danlin Xu AU - Linda Jolliffe AU - Maria-Luisa Alegre AU - Jeffrey A Bluestone AU - Marcus R Clark Y1 - 2002/09/01 UR - http://www.jrheum.org/content/29/9/1907.abstract N2 - OBJECTIVE: Treatment of autoimmune diseases with therapies that tolerize pathogenic lymphocytes may obviate the need for longterm global immunosuppression. In vitro, non-Fc receptor binding derivatives of anti-murine CD3 monoclonal antibodies tolerize type 1 T cells and stimulate type 2 T cells. Recently, a humanized non-FcR binding derivative of the anti-human CD3 Mab OKT3, huOKT3gamma1(ala-ala), has been described. We hypothesized that this Mab may be safe and efficacious in the treatment of type 1 T lymphocyte mediated chronic autoimmune diseases such as psoriatic arthritis (PsA). METHODS: In a Phase I/II trial, 7 patients with PsA were treated with escalating daily doses of huOKT3gamma1(ala-ala) for 12 to 14 days. Number of tender and swollen joints and a visual analog pain scale were used to rate disease activity at entry and Day 30 and Day 90 after treatment. RESULTS: At Day 30, 6 of 7 patients had > or = 75% improvement in the number of inflamed joints and an average 63% improvement on the patient pain scale. Two of 6 responders had sustained improvement at Day 90. No patient treated with an initial dose < or = 1 mg had significant side effects, nor did they have detectable increases in serum cytokines. One patient treated with 4 mg without escalation developed mild cytokine release symptoms associated with elevation of interleukin 10. Transient T cell depletion occurred following treatment with the maximum dose of 4 mg, which resolved by Day 30. Antiidiotypic antibodies developed in 2 patients; however, there was no concurrent decrease in efficacy. CONCLUSION: These data indicate that huOKT3gamma1(ala-ala) may be useful in treating PsA. ER -