title: Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial.
abstract: 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.
  
  
  CONCLUSIONS
  These data indicate that huOKT3gamma1(ala-ala) may be useful in treating PsA.
authors.affiliation: Section of Rheumatology, The Ben May Institute for Cancer Research, Chicago, Illinois, USA.
authors.forename: Tammy O
authors.initials: TO
authors.lastname: Utset
authors.forename: Julie A
authors.initials: JA
authors.lastname: Auger
authors.forename: Donna
authors.initials: D
authors.lastname: Peace
authors.forename: Robert A
authors.initials: RA
authors.lastname: Zivin
authors.forename: Danlin
authors.initials: D
authors.lastname: Xu
authors.forename: Linda
authors.initials: L
authors.lastname: Jolliffe
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Alegre
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Clark
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use*; D010147:Pain Measurement; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D016853:Muromonab-CD3