The potential interactions between PK, TNF level, BMI, and clinical outcomes have not been investigated adequately. of which the prevalence and effects are still insufficiently described. The objective of this review is to describe current data and understanding of the PK of GLM including serum concentrations of GLM and ADAbs in UC patients. AG-494 Better understanding of these parameters could lead to improved patient care with GLM. 2013; Paul 2014; Moore 2016]. Therapeutic drug monitoring (TDM), including measurement of antibodies against anti-TNF and drug trough levels are increasingly used to improve disease outcomes in IBD [Colombel 2012; Roblin 2014a; Ben-Horin and Chowers, 2014]. This monitoring can lead to optimization of drug dose in case of a loss of response. Treatment algorithms including TDM have been proposed to improve the outcome of anti-TNF therapy in IBD [Ben-Horin and Chowers, 2014]. Still, some patients with Rabbit Polyclonal to p53 a therapeutic drug level may relapse while others can remain in clinical remission despite low serum trough levels of anti-TNF [Steenholdt 2014a; Vande Casteele 2015]. Concomitant use of an immunomodulator can reduce ADAb development and is associated with higher drug trough levels [OMeara AG-494 2014]. Patients with a loss of clinical response to a first anti-TNF may regain response after a switch to another anti-TNF because ADAbs may not be crossreactive but are prone to develop ADAbs [Frederiksen 2014]. Golimumab (GLM) is a human immunoglobulin (Ig)G1 monoclonal antibody that received a French marketing license in 2009 2009. This monoclonal antibody binds to both the soluble and transmembrane bioactive forms of human TNF-, and thereby prevents the binding of TNF- to its receptors, inhibiting TNF bioactivity [Shealy 2010]. GLM is indicated for rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and ulcerative colitis (UC) [Sandborn 2014a]. Limited pharmacokinetic (PK) information is available in UC patients treated with GLM. Most PK data on GLM exposure-response relationship in UC AG-494 are from the PURSUIT induction and maintenance trials and recently published [Sandborn 2014a, 2014b; Rutgeerts 2015; Hyams 2016]. In PURSUIT trials, higher rates of clinical response and remission are reported in patients with GLM serum levels within the third and fourth quartile of distribution. There is, however, no consensus on a possible therapeutic level or cutoff associated with clinical response, remission, or any other outcome measure such as endoscopic healing in UC. This lack of a threshold value, and its validation with different assay techniques, makes it difficult to use GLM TDM in clinical practice. As with other anti-TNF agents, GLM is associated with development of ADAbs, of which the prevalence and effects are still insufficiently AG-494 described. Antibodies to anti-TNF may be transient [Vande Casteele 2013] and can have adverse effects (AEs) such as injection site reaction and loss of efficacy [Bingham 2015]. ADAbs influence the PK of GLM by increasing its clearance [Adedokun 2016b]. The objective of this review is to describe current data and understanding of the PK of GLM including serum concentrations of GLM and ADAbs in UC patients. Better understanding of these parameters could lead to improved patient care with GLM in UC. Review methodology We performed a literature review of all papers in English published in PubMed, Cochrane, Embase and in main learned society websites prior to August 2016. The term GLM was matched with the terms UC, biologics, PK, trough level and ADAb. Reports of congresses presentations and randomized controlled trials were also included. Mechanisms and schedule GLM is a humanized anti-TNF monoclonal antibody, administered through subcutaneous (SC) AG-494 injections. GLM blocks soluble and transmembrane TNF-, inhibiting TNF- receptor binding. However, compared with infliximab and adalimumab, GLM preclinical studies showed greater conformational stability and higher binding affinity for soluble and transmembrane TNF- [Shealy 2010]. GLM has been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for RA,.