557DIATSTAT™ Anti-cyclic Citrullinated Peptides
in Rheumatoid Arthritis
Effective disease management in RA requires early diagnosis and an accurate pre-
diction of which patients will have severe arthritis and require aggressive treatment.
There is a need for reliable biomarkers to assist clinical diagnosis and classify
patients into erosive and non-erosive forms at the earliest stage. Axis-Shield
DIASTAT anti-cyclic citrullinated peptides (CCP) detects antibodies against CPP
that are derived from fi laggrin, a protein associated with epidermal intermediate fi la-
ments. Antibodies to these CCPs correlate positively with the severity and incidence
of RA and its symptoms. Anti-CCP shows high sensitivity for RA (50-91 %) versus
rheumatoid factor (RF) (70-75 %). Similarly, anti-CCP shows a very high specifi city
(>97 %) versus RF (<66 %). RF is also present in other autoimmune diseases, infec-
tious diseases and healthy individuals. Anti-CCP in personalized medicine can:
- Detect early onset of RA disease
- Measure severity and erosiveness of RA
- Predict arthritis outcome
- Differentiate between autoimmune diseases
- Stratify RA patients for treatment with disease modifying antirheumatic drugs
- Be used to measure the effectiveness of treatment
Personalization of COX-2 Inhibitor Therapy
COX-2 inhibitors became one of the most widely used drugs for the management of
infl ammatory pain in rheumatoid arthritis. The best known of these were valdecoxib
(Pfi zer’s BEXTRA), celecoxib (Pfi zer’s Celebrex) and rofecoxib (Merck’s Vioxx).
These markedly reduced the gastrointestinal complications of NSAIDs that were
used previously for arthritis. However, an increased incidence of cardiovascular
complications led to the withdrawal of rofecoxib and restrictions on valdecoxib and
celecoxib. Some of the clinical trials for use of COX.2 inhibitors in prevention of
cancer and neurodegenerative diseases were also halted. In 2005, a panel of experts
voted unanimously to advise FDA that three leading painkillers – Celebrex, Bextra
and Vioxx – can cause worrisome heart problems. But it also advised against ban-
ning the drugs. There is a potential for application of pharmacogenetic studies to
identify patients who are susceptible to cardiovascular complications so that the use
of these drugs in such patients can be avoided.
Personalization of Infl iximab Therapy
Infl iximab, an anti-TNFα antibody, is effective in the treatment of several immuno-
infl ammatory diseases including rheumatoid arthritis. However, many patients
experience primary or secondary response failure, suggesting that individualization
Personalized Therapy of Rheumatoid Arthritis