553been carried out to defi ne therapeutic windows based on the blood levels of each
immunosuppressant, and relating those concentrations to clinical events. Although
pharmacokinetic- based approaches are currently used as useful tools to guide drug
dosing, they have several limitations. Pharmacogenomics might represent a com-
plementary support. Studies that have focused on polymorphisms of genes encod-
ing enzymes involved in drug metabolism, drug distribution, and pharmacological
targets, have shown promising results. Pharmacogenomics holds promise for
improvement in the ability to individualize pharmacological therapy based on the
patient’s genetic profi le.
Testing for thiopurine-S-methyltransferase polymorphisms is widely used in
clinical practice whereas other pharmacogenetic tests are much less frequently used.
Relatively good evidence has emerged for tacrolimus-related biomarkers; thus, their
application may be anticipated in the near future. Although the biomarkers related to
mycophenolate, sirolimus or other immunosuppressive drugs are promising, further
research is required to provide more robust evidence (Hronová et al. 2014 ).
Personalized Management of Patients with Lupus
Erythematosus
Systemic lupus erythematosus (SLE) affects >1 million persons in the US and
Western Europe. It is a chronic B cell mediated disease manifested by arthralgias,
fever, skin rash and end-stage renal disease. Although considered a prototypic auto-
immune disease, the hallmark of SLE is its heterogeneity. Accordingly, manifesta-
tions can vary widely from person to person, with the potential involvement of
virtually any bodily organ. Genetic abnormalities underlying this condition are
complicated, with diverse genetic polymorphisms described in different ethnic
groups, strongly suggesting that the actual pathology underlying the immunologic
disarray might not be the same for each patient. There is no cure for this disease.
Only three categories of drugs are currently approved for SLE: corticosteroids,
antimalarials, and low-dose aspirin. These are used for symptomatic relief or non-
specifi c immunosuppression. Until recently, antibodies to dsDNA or nuclear anti-
gens such as Sm antigen and phospholipids or measurement of complement
activation were used together with clinical scores as indicators of drug effi cacy in
clinical trials. Clinical scores are not satisfactory as there is a considerable lag period
between initiation of treatment and clinical effects. There are two potential biologic
drugs, rituximab (anti-CD20) and anti-CD22, but drug approval agencies are unable
to assess their real effi cacy because reliable biomarkers are not available.
The lack of reliable, specifi c biomarkers not only hampers clinical management
of SLE but also hinders development of new therapeutic agents. Based on available
data, several potential biomarkers for susceptibility, diagnosis, and disease activity
have been identifi ed. Despite the complexities of the many immunologic pathways
that are involved in SLE, biomarkers are emerging to characterize patient subgroups,
predict prognosis, indicate the exacerbations and remissions of SLE fl ares, and serve
as endpoints in the determination of the dosing and timing of immune- modulating
Personalized Management of Patients with Lupus Erythematosus