Based on the specificity and sensitivity
values derived from the ROC analysis of infliximab induction data, patients with serum infliximab concentrations www.selleckchem.com/products/ch5424802.html greater than 41 μg/mL have almost twice the likelihood of achieving clinical response at week 8 compared with those who do not achieve this target (positive likelihood ratio, 1.7). For more effective patient management; however, it would be preferable to predict the clinical outcome at week 8 based on earlier measurements. Accordingly, although our results showed that the preinfusion concentration at week 2 did not predict clinical response at week 8, the preinfusion concentration at week 6 may be a predictor of subsequent response. A likely explanation for this finding is that the serum infliximab concentration at week 6 is more reflective of drug clearance than the infliximab concentration at week 2, which reflects the initial phase of drug loading. With respect to maintenance infliximab therapy, the largest amount of data (ACT-1 and ACT-2 combined) was available at week 30, and the threshold at this time point was defined by ROC analysis at 3.7 μg/mL, with a PPV of 82% and an NPV of 51% for the maintenance of clinical response at week 30. These results show MAPK inhibitor that patients with a serum infliximab concentration greater than 3.7 μg/mL at steady-state are more than twice as likely to be in clinical response during maintenance
compared with patients who do not achieve this target (positive likelihood ratio, 2.3). Because the preinfusion serum infliximab concentration at week 30 is most representative of steady-state trough concentration for both ACT studies, more weight should be given to the threshold estimate from the ROC analyses at this time point compared with the week-54 maintenance time point in ACT-1. Nonetheless, our analysis showed that preinfusion serum infliximab concentrations at week 14 also may be predictive
of clinical response during maintenance. Specifically, a serum infliximab concentration of 5.1 μg/mL or higher at week 14 also was associated with clinical response at week 30. The serum infliximab concentration threshold of 5.1 μg/mL at week 14 is consistent with that defined by ROC analysis for week 30 (3.7 μg/mL) when consideration is given to the Phosphatidylinositol diacylglycerol-lyase fact that the concentration at week 14 theoretically is expected to be slightly higher than the concentration at week 30 because only 8 weeks (1 maintenance dose interval) have elapsed before the week-14 sampling, after the 3 induction doses at weeks 0, 2, and 6. Furthermore, the threshold serum infliximab concentration of 3.7 μg/mL is consistent with that estimated for patients with Crohn’s disease in a Crohn’s disease clinical trial evaluating infliximab in a new long term treatment regimen (ACCENT 1), in which a serum infliximab level of 3.5 μg/mL at week 14 was associated with sustained durable response through week 54.