Exposure-response characterization of tofacitinib efficacy in moderate to severe ulcerative colitis: Results from a dose-ranging phase 2 trial.

ABSTRACT:

Aims

Tofacitinib is an oral, small molecule JAK inhibitor being investigated for ulcerative colitis (UC). In a phase 2 dose-ranging study, tofacitinib demonstrated efficacy vs. placebo as UC induction therapy. In this posthoc analysis, we aimed to compare tofacitinib dose and plasma concentration as predictors of efficacy and identify covariates that determined efficacy in patients with UC.

Methods

One- and two-compartment pharmacokinetic models, with first-order absorption and elimination, were evaluated to describe plasma tofacitinib concentration-time data at baseline and week 8. Relationships between tofacitinib exposure (dose, average plasma drug concentration during a dosing interval at steady state [C_av,ss ] and trough plasma concentration at steady state [

SUBMITTER: Mukherjee A 

PROVIDER: S-EPMC5980553 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature