Early TDM can indicate in individual patients with fistulizing CD whether therapeutic drug exposure is achieved or not and guide subsequent rational treatment decisions to achieve rapid fistula closure. week 54 composite remission (OR: 2.05; 95%CI: 1.10-3.82; p=0.023). Based on receiver operating characteristic curve analysis, week 14 infliximab concentrations thresholds with combined maximal sensitivity and specificity of 20.2 g/mL at week 2, 15 g/mL at week 6, and 7.2 g/mL at week 14 were associated with week 14 composite remission. CONCLUSIONS: Higher post-induction infliximab concentrations are associated with early and long-term favorable therapeutic outcomes in patients with fistulizing CD. proposed that although infliximab concentrations 10.1 g/mL during maintenance therapy are associated with fistula healing, targeting even higher concentrations ( 20.2 g/mL) should be considered before changing to other therapeutic options.26 Limitations of our study include the lack of objective magnetic resonance imaging improvement of fistulas33, 34 and the fact that due Ginsenoside Rh2 to the design of the study only an association between higher serum infliximab concentrations and improved therapeutic outcomes can be established rather than causality. Strengths of our study include the large sample size, the use of stringent end-points and the use of high quality RCT data to investigate the association of infliximab concentrations with therapeutic outcomes in fistulizing CD. In conclusion, higher post-induction infliximab concentrations are associated with favorable early and log-term therapeutic outcomes in patients with fistulizing CD. Early TDM can indicate in individual patients with fistulizing CD whether therapeutic drug exposure is achieved Ginsenoside Rh2 or not and guide subsequent rational treatment decisions to achieve rapid fistula closure. However, whether, accelerated dosing in some patients with subtherapeutic drug exposure may lead to improved outcomes should be prospectively investigated. The results of this study may Ginsenoside Rh2 help better guide infliximab therapy in patients with fistulizing CD. ? STUDY HIGHLIGHTS WHAT IS KNOWN? There is a positive correlation between anti-TNF therapy concentration and favorable therapeutic outcomes in IBD. Preliminary data suggest that higher infliximab concentrations are associated with fistula healing in perianal fistulizing CD. The role of therapeutic drug monitoring for optimizing anti-TNF therapy fistulizing Ginsenoside Rh2 CD is largely unknown. WHAT IS NEW HERE? Higher post-induction infliximab concentrations are associated with early and long-term composite remission in patients with fistulizing CD. A week 6 infliximab concentration threshold of 15 g/ml stratified patients with fistulizing CD achieving early composite remission. A week 14 infliximab concentration threshold of 7.2 g/ml stratified patients with fistulizing CD achieving early composite remission. Supplementary Material Supplementary FileClick here to view.(241K, docx) Acknowledgments Financial support: KP is supported by the Ruth L. Kirschstein NRSA Institutional Research Training Grant 5T32DK007760-18. Potential competing interests: K.P. received a lecture fee from Mitsubishi Tanabe Pharma; Rabbit Polyclonal to Ezrin N.V.C. received research and consulting support from Takeda and UCB, research support from R-Biopharm and consulting support from Janssen, Pfizer, Progenity and Prometheus. V.J received has received has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, Celltrion; speakers fees from Takeda, Janssen, Shire, Ferring, Abbvie, Pfizer M.T.O: received consultancy fees from Janssen, AbbVie, UCB, Takeda, Pfizer, Merck, and Lycera, and received research grant support from UCB; A.S.C: received consultancy fees from AbbVie, Janssen, Takeda, EMD Serono, Arena pharmaceuticals, Alfasigma, Arsanis, Bacainn, Grifols, Prometheus, Samsung, and Pfizer, and research support from Inform Diagnostics; the remaining authors disclose no conflicts of interest..