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Biomarkers for Personalizing Therapy of Rheumatoid Arthritis
Vectra™ DA (Crescendo Bioscience), multi-biomarker blood test for RA may more
accurately identify early RA patients at risk for progression of joint damage when
compared to established disease activity measures. Prediction of radiographic pro-
gression (RP) in early RA would be very useful for optimal choice among available
therapies. The SWEFOT trial evaluated a multi-biomarker disease activity (MBDA)
score, based on 12 serum biomarkers as a baseline predictor for 1-year RP in early
RA (Hambardzumyan et al. 2014 ). Results suggest that when choosing initial treat-
ment in early RA the MBDA test may be clinically useful to identify a subgroup of
patients at low risk of RP.
Data demonstrate the Vectra DA algorithm score can identify patients at higher
risk for structural damage despite achieving remission by DAS28CRP (the 28-joint
disease activity score based on C-reactive protein). Among RA patients in
DAS28CRP remission, those who also had a high Vectra DA algorithm score are 2.3
times more likely to have progressive joint destruction during the following year.
Moreover, patients in remission as defi ned by the Vectra DA algorithm score have a
lower observed rate of radiographic progression compared to patients in remission
by DAS28CRP or by the Boolean criteria of American College of Rheumatology
and the European League Against Rheumatism.
RA demonstrates a high heterogeneity in clinical responses to treatment.
Although the effi cacy of biological therapy has undoubtedly been established, the
response differs considerably between individuals. This variability between indi-
viduals has stimulated search for biomarkers predictive of treatment response.
Pharmacogenomics underlying individual responses to drugs is rapidly developed
and has the potential of realizing the personalized therapy in RA (Xie et al. 2014 ).
Patients with RA are generally treated with tumor necrosis factor (TNF)-α inhibi-
tors as second-line therapy if an oral medication such as methotrexate is not adequate
to control the symptoms. If one anti-TNF therapy does not lead to adequate symptom
control, the current standard of care dictates switching to another approved anti-TNF
agent, even though response rates deteriorate with each cycle. Pilot research at
Biogen Idec and academic collaborators has developed a panel of gene expression
biomarkers with ~90 % positive and negative predictive values to identify individu-
als who did not achieve European League Against Rheumatism (EULAR) Disease
Activity Score (DAS)-28 good response after 14 weeks of treatment. Such a bio-
marker panel could be used as a diagnostic test to direct therapeutic options.
BATTER-UP (Biomarkers of Anti-TNF-α Therapy Effi cacy in Rheumatoid
arthritis to defi ne Unresponsive Patients) is a clinical study sponsored by Biogen-
Idec for adults diagnosed with RA to predict if a specifi c person with RA will be
helped by anti-TNF-α medications such as Remicade®, Enbrel®, Humira®,
Cimzia® and Simponi®. The primary outcome measure will be validation of the
ability of an 8-gene biomarker set to differentiate between patients who meet or do
not meet EULAR DAS-28 Good response criteria after treatment with anti-TNF
therapy. The aim is to develop a test that could help physicians decide whether or
not to prescribe an anti-TNF drug for a particular patient.
17 Personalized Approaches to Immune Disorders