555examining their DNA for chemical tags – methyl groups – that could attach them-
selves to genes and turn them on or off (Liu et al. 2013 ). Results showed that the
chemical tags may help determine if a person with a gene that increases risk of
developing RA actually gets the disease. There were subjects in the control group
who had gene variations associated with RA risk, but they did not have those four
chemical tags and did not have the disease.
Variations in the Effectiveness of Various Treatments of RA
Numerous drugs are used in the treatment of RA. Some are for relief of pain whereas
others are aimed at modifying the disease process. There are large differences in the
effectiveness of disease modifying anti – rheumatic drugs (DMARD) from one per-
son to the next. Adverse drug reactions caused by DMARD can also occur in some
patients but not in others. Because traditional pharmacotherapy in rheumatology has
been empirical and because of the slow acting nature of many anti-rheumatic medi-
cations, the risk of signifi cant side effects and the increasing armamentarium of drugs
available, pharmacogenetics is particularly relevant to rheumatology. There are many
scientifi c and non-scientifi c concerns that should be addressed in future studies.
One possible cause of the differences in the effectiveness and adverse drug reac-
tions is genetic variation in how individuals metabolize drugs. Various studies have
revealed the relationship between genetic polymorphisms of drug metabolizing
enzymes and the effi cacy of DMARDs in patients with RA, suggesting pharmaco-
genetics is applicable to the treatment of rheumatoid arthritis. Methotrexate (MTX)
remains the most commonly used disease modifying antirheumatic drug in RA
because of its low cost and experience in its use, despite the availability of new
treatments such as lefl unomide and the anti-cytokine agents. However, a signifi cant
number of patients with RA either do not benefi t from the drug or are unable to
tolerate it. Pharmacogenetic approaches may help optimize treatment with MTX,
and also other agents in RA.
Haplotype patterns in the IL-1 gene cluster infl uence why some individuals
respond differently to infl ammatory stimuli and thereby develop a different disease
pattern or respond differently to therapy. Interleukin Genetics is generating more
detailed information on new haplotypes in the IL-1 gene cluster from its high-
density SNP mapping project. One of the primary clinical applications that
Interleukin is pursuing is the development of a pharmacogenetic test to assist physi-
cians in deciding which therapeutic drugs to prescribe patients with rheumatoid
arthritis. Some published data suggest that a patient’s IL-1 genotype may predict his
or her response to drug therapy.
Pharmacogenomic studies on methotrexate, sulfasalazine and TNF-α inhibitors
have been reported, suggesting that the pharmacogenomic approach may be useful
for the treatment of RA. Although there other points to be considered before the
translation of the pharmacogenomic date into clinical practice, pharmacogenomics
is an important tool for development of individualized medicine in the treatment of
RA (Taniguchi et al. 2007 ).
Personalized Therapy of Rheumatoid Arthritis