Pharmacogenomics of interferon-β in multiple sclerosis: what has been accomplished and how can we ensure future progress?

Cytokine Growth Factor Rev. 2015 Apr;26(2):249-61. doi: 10.1016/j.cytogfr.2014.10.008. Epub 2014 Oct 31.

Abstract

Multiple sclerosis (MS) is a progressive disorder of the central nervous system, often resulting in significant disability in early adulthood. The field of pharmacogenomics holds promise in distinguishing responders from non-responders to drug treatment. Most studies on genetic polymorphisms in MS have addressed treatment with interferon-β, yet few findings have been replicated. This review outlines the barriers that currently hinder the validity, reproducibility, and inter-study comparison of pharmacogenomics research as it relates to the use of interferon-β. Notably, statistical power, varying definitions of responder status, varying assay and genotyping methodologies, and anti-interferon-β neutralizing antibodies significantly confound existing data. Future work should focus on addressing these factors in order to optimize interferon-β treatment outcomes in MS.

Keywords: Interferon-β; Multiple sclerosis; Neutralizing antibodies; Pharmacogenomics; Responders.

Publication types

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

MeSH terms

  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Confounding Factors, Epidemiologic
  • Genetic Testing
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interferon-beta / immunology
  • Interferon-beta / therapeutic use*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Pharmacogenetics*
  • Polymorphism, Single Nucleotide
  • Reproducibility of Results

Substances

  • Antibodies, Neutralizing
  • IRF5 protein, human
  • Interferon Regulatory Factors
  • Interferon-beta