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Genetic variants that predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis: current

Robert M Plenge1, Lindsey A Criswell

  • 1Division of Rheumatology, Immunology and Allergy, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.

Current Opinion in Rheumatology
|March 20, 2008
PubMed
Abstract

Insights

Predicting response to tumor necrosis factor alpha (TNF) inhibitors in rheumatoid arthritis remains challenging. Current genetic studies are limited, highlighting the need for larger, genome-wide investigations to identify reliable DNA biomarkers for anti-TNF therapy.

Area of Science:

  • Genetics
  • Immunology
  • Rheumatology

Background:

  • Tumor necrosis factor alpha (TNF) inhibitors are crucial for rheumatoid arthritis (RA) treatment.
  • Predicting patient response to anti-TNF therapy is currently not possible through clinical or biomarker assessments.

Purpose of the Study:

  • To review existing genetic association studies searching for DNA biomarkers predicting response to anti-TNF therapy in RA.

Main Methods:

  • Review of published genetic association studies.
  • Focus on candidate gene approaches, particularly within the major histocompatibility complex.

Main Results:

  • Limited number of genetic variants and small patient cohorts (approx. 1000 RA patients) studied to date.
  • No single genetic factor has been unequivocally linked to anti-TNF treatment response.
  • Some evidence suggests major histocompatibility complex alleles may influence response.

Conclusions:

  • Further research is essential to understand the genetic underpinnings of anti-TNF therapy response in RA.
  • Future studies should employ unbiased, genome-wide association studies (GWAS) in large patient cohorts.
  • Larger sample sizes are needed to detect modest genetic effect sizes.

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