Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor that is being investigated for juvenile idiopathic arthritis (JIA). Here, we report the pharmacokinetics (PK), safety, and taste acceptability of tofacitinib following multiple oral doses in patients (pts) 2–<18 years (yrs) old with active JIA.

Methods: Data were obtained from an open-label, non-randomized, multicenter, Phase I study (NCT01513902) where JIA pts were given 5 mg adult equivalent (based on body weight) of tofacitinib (tablet or solution) twice daily (BID) for 5 days (Table). There were 3 cohorts (COH) based on pt age, COH1: 12–<18 yrs, COH2: 6–<12 yrs, and COH3: 2–<6 yrs, with a target enrollment per group of ≥8 JIA pts for N=≥24 evaluable pts completing the study. Pts were enrolled in a step-wise approach beginning with the older age COH first. Subsequent younger age COH were enrolled following confirmation of safety and PK from the previous COH. PK parameters of tofacitinib were calculated using non-compartmental analysis of plasma concentration (conc)-time data. Taste acceptability of the solution formulation was listed and categorically summarized (frequency and %).

Results: 26 pts (COH1 [N=8], COH2 [N=9], and COH3 [N=9]) were included in this analysis. Pts’ age ranged from 2–17 years; all were white except for one; there were 17 females and 9 males. Baseline disease characteristics were similar across all COH. All exposure metrics including geometric mean (GM) area under the conc-time curves (AUC_tau), maximum (C_max), minimum (C_min) and predose (C_trough) conc were lower in COH2 relative to those in COH1; however, due to higher doses in COH3 (modified after interim analysis of COH1 and 2), the mean AUC_tau in COH3 was comparable to COH1. GM apparent volume of distribution (V_z/F) decreased with age (COH1=104.9 L, COH2=71.0 L, COH3=51.4 L). Average terminal half-lives (t_½) were COH1=2.62 h, COH2=1.95 h, and COH3=1.77 h. GM tofacitinib CL/F were 53%, 39%, and 11% higher in COH1, COH2, and COH3 pts, respectively, vs adult RA pts (18.4 L/h) receiving tofacitinib 5 mg BID. GM CL/F and V/F parameters were similar between males and females. Tofacitinib, administered over 5 days as multiple dose tablets or solution formulation, was well tolerated and taste for the solution formulation was found acceptable in children with active JIA. No serious adverse events or new safety signals were identified.

Conclusion: PK results from this study established dosing regimens for pts aged ≥2 years to be used in the upcoming efficacy and safety studies of tofacitinib in JIA pts. Tofacitinib was well tolerated in this study in JIA pts. Overall, pts found the taste of the tofacitinib solution formulation to be acceptable.