Evaluation of safety and clinical activity of multiple doses of the anti-CD80 monoclonal antibody, galiximab, in patients with moderate to severe plaque psoriasis

Alice B. Gottlieb, Sewon Kang, Kenneth G. Linden, Mark Lebwohl, Alan Menter, Ahsan A. Abdulghani, Michael Goldfarb, Nicole Chieffo, Mark C. Totoritis

Research output: Contribution to journalArticle

Abstract

Background: Reduction in lesional, activated T cells induces improvement in psoriatic plaques. Galiximab (IDEC-114), an IgG1 anti-CD80 antibody, binds to CD80, a costimulatory molecule involved in T-cell activation. Objective: A Phase I/II, multidose, multischedule, dose-finding study of galiximab to evaluate safety, pharmacokinetics, and clinical activity was conducted in 35 patients with moderate to severe plaque psoriasis. Methods: Seven cohorts of five patients received galiximab intravenously on three different schedules at different dose levels. Results: Adverse events (AEs) commonly occurred as mild and self-limiting. Improvements were observed in most cohorts without evidence of a dose response in Psoriasis Area and Severity Index (50% or greater reduction in PASI score in 40% of patients), Physician's Global Psoriasis Assessment (PGA rating of Good or above in 57% of patients), and Psoriasis Severity Scale (PSS, baseline mean of 7.6 decreased by Study Day 127 to 5.0). An association was observed between reduction in CD3+ cell count in histologic studies and reduction in PASI score. No antibodies to galiximab were detected. Conclusion: Galiximab appears to be safe and well tolerated with preliminary evidence of clinical and histologic response.

Original languageEnglish (US)
Pages (from-to)28-37
Number of pages10
JournalClinical Immunology
Volume111
Issue number1
DOIs
StatePublished - Apr 2004
Externally publishedYes

Fingerprint

Psoriasis
Monoclonal Antibodies
Safety
Prostaglandins A
T-Lymphocytes
galiximab
Anti-Idiotypic Antibodies
Appointments and Schedules
Pharmacokinetics
Cell Count
Immunoglobulin G
Physicians
Antibodies

Keywords

  • ADCC
  • Adverse event
  • AE
  • Antibody-dependent, cell-mediated cytotoxicity
  • Antigen-presenting cells
  • APCs
  • Area under the curve
  • AUC
  • CDC
  • Complement-dependent cytotoxicity
  • CTLA-4
  • Cytotoxic T lymphocyte-associated antigen-4
  • Galiximab
  • ICAM-1
  • PASI
  • Psoriasis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Evaluation of safety and clinical activity of multiple doses of the anti-CD80 monoclonal antibody, galiximab, in patients with moderate to severe plaque psoriasis. / Gottlieb, Alice B.; Kang, Sewon; Linden, Kenneth G.; Lebwohl, Mark; Menter, Alan; Abdulghani, Ahsan A.; Goldfarb, Michael; Chieffo, Nicole; Totoritis, Mark C.

In: Clinical Immunology, Vol. 111, No. 1, 04.2004, p. 28-37.

Research output: Contribution to journalArticle

Gottlieb, Alice B. ; Kang, Sewon ; Linden, Kenneth G. ; Lebwohl, Mark ; Menter, Alan ; Abdulghani, Ahsan A. ; Goldfarb, Michael ; Chieffo, Nicole ; Totoritis, Mark C. / Evaluation of safety and clinical activity of multiple doses of the anti-CD80 monoclonal antibody, galiximab, in patients with moderate to severe plaque psoriasis. In: Clinical Immunology. 2004 ; Vol. 111, No. 1. pp. 28-37.
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AU - Kang, Sewon

AU - Linden, Kenneth G.

AU - Lebwohl, Mark

AU - Menter, Alan

AU - Abdulghani, Ahsan A.

AU - Goldfarb, Michael

AU - Chieffo, Nicole

AU - Totoritis, Mark C.

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AB - Background: Reduction in lesional, activated T cells induces improvement in psoriatic plaques. Galiximab (IDEC-114), an IgG1 anti-CD80 antibody, binds to CD80, a costimulatory molecule involved in T-cell activation. Objective: A Phase I/II, multidose, multischedule, dose-finding study of galiximab to evaluate safety, pharmacokinetics, and clinical activity was conducted in 35 patients with moderate to severe plaque psoriasis. Methods: Seven cohorts of five patients received galiximab intravenously on three different schedules at different dose levels. Results: Adverse events (AEs) commonly occurred as mild and self-limiting. Improvements were observed in most cohorts without evidence of a dose response in Psoriasis Area and Severity Index (50% or greater reduction in PASI score in 40% of patients), Physician's Global Psoriasis Assessment (PGA rating of Good or above in 57% of patients), and Psoriasis Severity Scale (PSS, baseline mean of 7.6 decreased by Study Day 127 to 5.0). An association was observed between reduction in CD3+ cell count in histologic studies and reduction in PASI score. No antibodies to galiximab were detected. Conclusion: Galiximab appears to be safe and well tolerated with preliminary evidence of clinical and histologic response.

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