Although infliximab is indicated for the treatment

of UC only as a 5-mg/kg dose regimen, Talazoparib mw for the purpose of these analyses, data from patients who received the 10-mg/kg dose regimen in the ACT-1 and ACT-2 trials were included for a more robust evaluation and interpretation of the concentration-response relationship. Clinical outcomes were assessed using the Mayo score at week 8 (ACT-1 and ACT-2), at week 30 (ACT-1 and ACT-2), and at week 54 (ACT-1 only). Clinical response, defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, and with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1, was the primary end point for both the ACT-1 and ACT-2 trials. Clinical remission was defined as a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point. Mucosal healing was defined by an endoscopy subscore of 0 or 1. For PK evaluations, patients were followed up through week 54 in ACT-1 or through week 42 in ACT-2. In ACT-1, blood samples for determining serum infliximab concentrations were drawn just before and 1 hour after the infusions at weeks 0, 2, 6, 14, and 46, and just before the infusions at

weeks 30 and see more 38. Additional 4��8C blood samples for determination of serum infliximab concentrations were drawn at the week-8 and week-54 nondosing visits (Supplementary Figure 1). In ACT-2, blood samples were drawn

just before and 1 hour after the infusions at weeks 0 and 2, and just before the infusions at weeks 6 and 14. Additional blood samples for serum infliximab concentration analysis were drawn at the week-8, week-30, and week-42 nondosing visits (Supplementary Figure 1). Serum infliximab concentrations were determined using a validated enzyme-linked immunosorbent assay,16 with a lower limit of quantification of 0.1 μg/mL. Of the 484 patients randomized to infliximab (5 or 10 mg/kg) in the ACT-1 and ACT-2 trials, 482 received at least 1 infusion and had appropriate serum infliximab concentration data. ATI were determined using an antigen-bridging enzyme immunoassay.16 Similar to other enzyme immunoassays, this assay was susceptible to drug interference and was not able to detect ATI accurately in the presence of a measurable infliximab concentration. For the purpose of this analysis, patients were classified as positive if ATI were detected in their serum samples at any visit, whereas all other patients were regarded as nonpositive for ATI. The patient population for these analyses included only those who received at least 1 infusion of infliximab at a dose of 5 or 10 mg/kg.