Biology Reference
In-Depth Information
CHAPTER
3
Personalized Healthcare in
A
utoimmune Disea
ses
Cornelis L. Verweij
1
, Brandon W. Higgs
2
,
Yihong Yao
2
1
Department of Pathology, VU University Medical Center, Amsterdam,
The Netherlands
2
MedImmune, LLC, Gaithersburg, Maryland
3.1 INTRODUCTION
One of the major challenges in the treatment of autoimmune diseases is the introduction
of tailored therapies, or personalized medicine, to optimize the treatment efficacy for the
individual patient, and to minimize the risk of adverse effects and unnecessary healthcare
expenses. The concept of a personalized form of medicine has attracted interest in the search
for clinical and molecular biomarkers to dissect responders from non-responders and to
monitor drug efficacy. Mechanistically, there are two phases to explain the failure to respond
to therapy with a biologic. Primary non-responders are characterized by a direct failure to
reach the clinical endpoint, whereas the secondary non-responsiveness develops following
a period of good response. One of the main reasons for the second phase of non-responsive-
ness can be attributed to the development of neutralizing antibodies, which takes at least six
months to develop. It is believed that pathophysiological features at baseline and
/
or varying
pharmacological effects among patients could be the underlying differences between a good
and poor response in the primary phase.
Research efforts during the last decade have made progress in the identification of poten-
tial clinically relevant biomarkers to predict the primary non-response to biologic treatment
and in monitoring drug efficacy. In this chapter we provide an overview of relevant bio-
markers (predictive and pharmacodynamic markers) in the field of psoriasis, systemic lupus
erythematosus (SLE), myositis, rheumatoid arthritis (RA), and multiple sclerosis (MS) which
have potential clinical utility and provide a deeper understanding of the different molecu-
lar mechanisms underlying autoimmune diseases. These biomarkers have the potential to
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