Long-Term Pharmacokinetics of Body Surface Area-Adjusted Doses of Golimumab Following Repeated Subcutaneous Administrations in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis

BACKGROUND/PURPOSE: To assess the pharmacokinetics (PK) and PK-efficacy correlations of body surface area (BSA)-adjusted dosing of 30 mg/m2golimumab administered subcutaneously (SC) every 4 weeks (q4w) methotrexate (MTX) through Week 48 in pediatric patients (ages 2 to 18years) with juvenile idiopathic arthritis (JIA).METHODS: GO-KIDS is a randomized-withdrawal, double-blind, placebo-controlled, parallel-group, multicenter Phase 3 trial of SC golimumab 30mg/m2 (maximum 50 mg) q4w MTX (10–30 mg/m2/week) in pediatricpatients with active JIA despite current MTX therapy (median 15 mg/week).PK, safety, and efficacy evaluations were performed q4w through week 16.At Week 16, patients who were ACR JIA 30 responders were random-ized (1:1) to 30 mg/m 2 golimumab or placebo q4wks through Week 48with GLM reinstituted upon flare (defined as per JIA ACR flarecriteria) or initiation of new DMARDS, biologics, systemic immuno-suppressives. Serum trough concentrations were also obtained atWeeks 12, 16, 24 and 48. Serum golimumab trough concentrations for154 patients were determined via a validated immunoassay. Therelationships of ACR pediatric 30 response and disease flare statuswith steady-state trough levels at Week 48 were assessed.RESULTS: Trough serum golimumab concentrations in patients receivingSC 30 mg/m2 golimumab q4w through Week 48 were maintained over time.Steady-state trough golimumab levels were similar across different agegroups, and were also similar to those seen in adult RA patients who received50 mg SC q4w in Phase III clinical trials. There were no apparent differencesin pediatric ACR JIA 30 response rates and disease flare rates among the 4groups of JIA patients categorized by the 4 quartiles of steady-state troughgolimumab levels at Week 48. In addition, there were no apparent PKdifferences between patients who did and did not experience disease flares inthe randomized golimumab group. Mean (SD) and median trough serumgolimumab concentrations (mg/mL) by age groups and body weight quartilesare presented in the table.CONCLUSION: Treatment with 30 mg/m2 SC golimumab q4w MTXresulted in sustained steady-state trough serum golimumab concentrationsover time. The PK/efficacy correlation analyses demonstrated that theBSA-adjusted dosing regimen of 30 mg/m2 SC golimumab q4w providedadequate drug exposure for the desired efficacy.