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 language | English |
|---|---|
| Pages (from-to) | 1907-1913 |
| Number of pages | 7 |
| Journal | Journal of Rheumatology |
| Volume | 29 |
| Issue number | 9 |
| State | Published - Sep 1 2002 |
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Keywords
- Clinical trial
- Monoclonal antibody
- OKT3
- Psoriatic arthritis
- Spondyloarthropathy
ASJC Scopus subject areas
- Rheumatology
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Modified anti-CD3 therapy in psoriatic arthritis
T2 - A Phase I/II clinical trial
AU - Utset, Tammy O.
AU - Auger, Julie A.
AU - Peace, Donna
AU - Zivin, Robert A.
AU - Xu, Danlin
AU - Jolliffe, Linda
AU - Alegre, Maria Luisa
AU - Bluestone, Jeffrey A.
AU - Clark, Marcus R.
PY - 2002/9/1
Y1 - 2002/9/1
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, 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.
AB - 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.
KW - Clinical trial
KW - Monoclonal antibody
KW - OKT3
KW - Psoriatic arthritis
KW - Spondyloarthropathy
UR - http://www.scopus.com/inward/record.url?scp=0036733642&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036733642&partnerID=8YFLogxK
M3 - Article
C2 - 12233885
AN - SCOPUS:0036733642
VL - 29
SP - 1907
EP - 1913
JO - Journal of Rheumatology
JF - Journal of Rheumatology
SN - 0315-162X
IS - 9
ER -