Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial

Arthritis Rheum. 2002 Dec;46(12):3251-8. doi: 10.1002/art.10681.

Abstract

Objective: To evaluate the safety and efficacy of a humanized monoclonal antibody against CD154 (IDEC-131) in patients with active systemic lupus erythematosus (SLE).

Methods: In this phase II, double-blind, placebo-controlled, multiple-center, multiple-dose study, 85 patients with mild-to-moderately active SLE were randomized to receive 6 infusions of IDEC-131, ranging from 2.5 mg/kg to 10.0 mg/kg, or placebo over 16 weeks. Efficacy was assessed at week 20, primarily by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and secondarily, by multiple measures of disease activity. Safety was assessed through week 28 by clinical and laboratory evaluation. Immunogenicity studies were also performed.

Results: SLEDAI scores improved from the baseline levels of disease activity in all groups, including the placebo group. However, these scores were not statistically different among the IDEC-131 treatment and placebo groups at week 20. Evaluations of secondary variables did not indicate significant differences between the IDEC-131 treatment and placebo groups. The type and frequency of adverse events were similar between the IDEC-131 and placebo groups.

Conclusion: IDEC-131 administered at doses ranging 2.5-10.0 mg/kg over 16 weeks was safe and well tolerated in patients with SLE. Efficacy of the drug compared with placebo was not demonstrated. There were statistically significant improvements from baseline in all groups, including the placebo group.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • CD40 Ligand / immunology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / physiopathology*
  • Male
  • Middle Aged
  • Placebos
  • Safety
  • T-Lymphocytes / physiology*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Placebos
  • CD40 Ligand