Modified anti-CD3 therapy in psoriatic arthritis

A Phase I/II clinical trial

Tammy O. Utset, Julie A. Auger, Donna Peace, Robert A. Zivin, Danlin Xu, Linda Jolliffe, Maria Luisa Alegre, Jeffrey A. Bluestone, Marcus R. Clark

Research output: Contribution to journalArticle

118 Citations (Scopus)

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, huOKT3γ1(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 huOKT3γ1(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 ≥ 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 ≤ 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 huOKT3γ1(ala-ala) may be useful in treating PsA.

Original languageEnglish
Pages (from-to)1907-1913
Number of pages7
JournalJournal of Rheumatology
Volume29
Issue number9
StatePublished - Sep 1 2002

Fingerprint

Phase II Clinical Trials
Clinical Trials, Phase I
Psoriatic Arthritis
T-Lymphocytes
Autoimmune Diseases
Therapeutics
Joints
Cytokines
Muromonab-CD3
Pain Measurement
Interleukin-10
Immunosuppression
Chronic Disease
Monoclonal Antibodies
Lymphocytes
Pain
Antibodies
Serum

Keywords

  • Clinical trial
  • Monoclonal antibody
  • OKT3
  • Psoriatic arthritis
  • Spondyloarthropathy

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

Cite this

Utset, T. O., Auger, J. A., Peace, D., Zivin, R. A., Xu, D., Jolliffe, L., ... Clark, M. R. (2002). Modified anti-CD3 therapy in psoriatic arthritis: A Phase I/II clinical trial. Journal of Rheumatology, 29(9), 1907-1913.

Modified anti-CD3 therapy in psoriatic arthritis : A Phase I/II clinical trial. / Utset, Tammy O.; Auger, Julie A.; Peace, Donna; Zivin, Robert A.; Xu, Danlin; Jolliffe, Linda; Alegre, Maria Luisa; Bluestone, Jeffrey A.; Clark, Marcus R.

In: Journal of Rheumatology, Vol. 29, No. 9, 01.09.2002, p. 1907-1913.

Research output: Contribution to journalArticle

Utset, TO, Auger, JA, Peace, D, Zivin, RA, Xu, D, Jolliffe, L, Alegre, ML, Bluestone, JA & Clark, MR 2002, 'Modified anti-CD3 therapy in psoriatic arthritis: A Phase I/II clinical trial', Journal of Rheumatology, vol. 29, no. 9, pp. 1907-1913.
Utset TO, Auger JA, Peace D, Zivin RA, Xu D, Jolliffe L et al. Modified anti-CD3 therapy in psoriatic arthritis: A Phase I/II clinical trial. Journal of Rheumatology. 2002 Sep 1;29(9):1907-1913.
Utset, Tammy O. ; Auger, Julie A. ; Peace, Donna ; Zivin, Robert A. ; Xu, Danlin ; Jolliffe, Linda ; Alegre, Maria Luisa ; Bluestone, Jeffrey A. ; Clark, Marcus R. / Modified anti-CD3 therapy in psoriatic arthritis : A Phase I/II clinical trial. In: Journal of Rheumatology. 2002 ; Vol. 29, No. 9. pp. 1907-1913.
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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, huOKT3γ1(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 huOKT3γ1(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 ≥ 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 ≤ 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 huOKT3γ1(ala-ala) may be useful in treating PsA.",
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