Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-alpha monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris

J Am Acad Dermatol. 2003 Jan;48(1):68-75. doi: 10.1067/mjd.2003.10.

Abstract

Objective: Infliximab monotherapy provided a rapid and high degree of clinical benefit in patients with moderate to severe psoriasis in a previously conducted trial. Herein we describe the pharmacodynamic and pharmacokinetic results observed in this clinical trial.

Methods: Patients with psoriasis received 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6. Immunohistochemical analysis of lesional (weeks 0, 2, 10) and nonlesional (week 0) biopsies was conducted. Median infliximab half-life and peak serum concentrations over time were calculated.

Results: Infliximab immunotherapy resulted in rapid and dramatic decreases in epidermal inflammation and normalization of keratinocyte differentiation in psoriatic plaques; these changes preceded maximal clinical response. Infliximab concentrations were maintained above the detection limit (0.1 mg/mL) in the majority of patients through week 14.

Conclusion: The clinical and immunohistologic data demonstrate a pivotal role for tumor necrosis factor-alpha in the pathogenesis of psoriasis and support further development of drugs targeting tumor necrosis factor-alpha.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Dermatologic Agents / administration & dosage
  • Dermatologic Agents / therapeutic use*
  • Humans
  • Immunohistochemistry
  • Infliximab
  • Middle Aged
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Antibodies, Monoclonal
  • Dermatologic Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab