Long-term Treatment of Multiple Sclerosis With Glatiramer Acetate: Natural History of the Subtypes of Anti-Glatiramer Acetate Antibodies and Their Correlation With Clinical Efficacy

J Neuroimmunol. 2010 Mar 30;220(1-2):125-30. doi: 10.1016/j.jneuroim.2010.01.009. Epub 2010 Feb 13.

Abstract

A retrospective phase IV study was designed to evaluate the anti-GA antibody subtypes, test their in vitro neutralizing activity and correlate these parameters with the clinical efficacy, in long-term GA treatment of MS patients. Serum samples from 153 MS patients, 126 treated with GA for 2 to 15 years (mean 6.6 years) and 27 treated for <2 years, were collected. Anti-myelin basic protein (MBP) and anti-GA antibodies were measured by specific ELISA. Neutralizing activity was determined by the capacity of the serum to inhibit the proliferation of GA-specific T-cells. Anti-GA antibodies were detected even after very long treatment periods, although at lower levels. Anti-MBP reactivity remained consistently negative. The IgG2 isotype of anti-GA antibodies and the multiple sclerosis severity scale (MSSS) was lower in the long-term treated patients P=0.0003 and 0.016 respectively. The neutralizing activity of anti-GA antibodies was insignificant. Our results indicate that the clinical efficacy of GA treatment could be associated with a decrease in anti-GA IgG2 isotype in long-term GA-treated patients.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study

MeSH terms

  • Adult
  • Antibodies, Anti-Idiotypic
  • Antibodies, Neutralizing / analysis
  • Antibodies, Neutralizing / blood*
  • Antibodies, Neutralizing / classification
  • Autoantibodies / analysis
  • Autoantibodies / blood
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cross Reactions / immunology
  • Drug Administration Schedule
  • Drug Resistance / immunology
  • Female
  • Glatiramer Acetate
  • Humans
  • Immunoglobulin G / analysis
  • Immunoglobulin G / blood
  • Immunoglobulin Isotypes / immunology
  • Immunosuppressive Agents / immunology*
  • Immunosuppressive Agents / pharmacology
  • Israel
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology*
  • Myelin Basic Protein / immunology
  • Peptides / immunology*
  • Peptides / pharmacology
  • Retrospective Studies
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Time
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Neutralizing
  • Autoantibodies
  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • Immunosuppressive Agents
  • Myelin Basic Protein
  • Peptides
  • Glatiramer Acetate