, 2008). However, over 30% of patients fail to respond to anti-TNF-α therapy, and many who initially respond later require higher or more frequent dosing due to a failure to maintain the initial response, especially in the IBD patient population

(Hanauer et al., 2002, Gisbert and Panes, 2009 and Regueiro et al., 2007). There is now compelling evidence that demonstrates that the loss of response in these patients is a result of a failure to achieve and maintain adequate therapeutic drug levels in blood and/or from the formation of anti-drug antibodies (Miheller et al., 2012). Anti-drug antibodies could cause adverse events such as serum sickness and hypersensitivity reactions (Brennan et al., 2010 and Emi et al., 2010), and it is hypothesized that their formation LBH589 molecular weight may also increase drug clearance and/or neutralize the drug effect, thereby potentially contributing to the loss of response. Moreover, recent data suggest that the standard dosing regimen for TNF-α-blocking drugs may be suboptimal in some IBD patients,

and an individualized dosing regimen to achieve therapeutic drug levels may be important to maximize the initial find protocol drug response and to maintain remission (Colombel et al., 2012). Therefore, accurate monitoring of serum drug and anti-drug antibody levels should be an important part of therapy for patients being treated with protein-based drugs. While monitoring for serum drug levels and for the formation of anti-drug antibodies are routine components of early drug development and are mandatory during clinical trials (Shankar et

al., 2006), these activities have generally not been adopted in clinical practice. This deficiency may be partially explained by technical issues of the available monitoring assays, which limit their utility as part of routine clinical practice. Current methods for the assessment of anti-drug diglyceride antibodies and drug levels in serum mainly utilize the bridging ELISA method (Baert et al., 2003) and, occasionally, the radioimmunoassay (RIA) method (Aarden et al., 2008). However, a major limitation of the bridging ELISA methods in measuring anti-drug antibody levels is the inability to accurately detect the antibodies in the presence of the drug in circulation due to cross-interference. Specifically, the circulating drug interferes with the capture of anti-drug antibodies by the same drug initially coated on the ELISA plate, thus limiting the ELISA’s ability to detect anti-drug antibodies, resulting in a lower sensitivity for detection in the presence of IFX. Therefore, ELISA methods can only measure anti-drug antibodies accurately when there is no drug in circulation, which significantly limits its clinical utility.