A36: Long‐term Pharmacokinetics of Body Surface Area‐Adjusted Doses of Golimumab Following Repeated Subcutaneous Administrations in Pediatric Patients With Polyarticular Juvenile Idiopathic Arthritis
Authors: Leu Jocelyn H. , Mendelsohn Alan , Ford Joyce , Davis Hugh M. , Zhou Honghui , Xu Z. 
Published: March 2014

Background/Purpose:

To assess the pharmacokinetics (PK) and PK‐efficacy correlations of body surface area (BSA)‐adjusted dosing of 30 mg/m2 golimumab administered subcutaneously (SC) every 4 weeks (q4w) + methotrexate (MTX) through Week 48 in pediatric patients (ages 2 to <18 years) 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 30 mg/m2 (maximum 50 mg) q4w + MTX (10/N30 mg/m2/week) in pediatric patients 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 randomized (1:1) to 30 mg/m2 golimumab or placebo q4wks through Week 48 with GLM reinstituted upon flare (defined as per JIA ACR flare criteria) or initiation of new DMARDS, biologics, systemic immunosuppressives. Serum trough concentrations were also obtained at Weeks 12, 16, 24 and 48. Serum golimumab trough concentrations for 154 patients were determined via a validated immunoassay. The relationships of ACR pediatric 30 response and disease flare status with steady‐state trough levels at Week 48 were assessed.

Results:

Trough serum golimumab concentrations in patients receiving SC 30 mg/m2 golimumab q4w through Week 48 were maintained over time. Steady‐state trough golimumab levels were similar across different age groups, and were also similar to those seen in adult RA patients who received 50 mg SC q4w in Phase III clinical trials. There were no apparent differences in pediatric ACR JIA 30 response rates and disease flare rates among the 4 groups of JIA patients categorized by the 4 quartiles of steady‐state trough golimumab levels at Week 48. In addition, there were no apparent PK differences between patients who did and did not experience disease flares in the randomized golimumab group. Mean (SD) and median trough serum golimumab concentrations (mg/mL) by age groups and body weight quartiles are presented in the .

Age Groups (Years)

2–6
≥6 to 12
≥12
Combined

Week 12

Mean (SD)
1.42 (0.744)
0.95 (0.593)
1.21 (0.711)
1.14 (0.685)

Median
1.77
0.92
1.29
1.46

Week 16

Mean (SD)
1.17 (0.650)
0.96 (0.721)
1.24 (0.836)
1.13 (0.780)

Age Groups (Years)

2–6
≥6 to 12
≥12
Combined

Median
1.22
0.89
1.23
1.10

Week 24

Mean (SD)
1.30 (0.833)
1.08 (0.876)
1.23 (1.003)
1.19 (0.927)

Median
1.57
1.12
1.08
1.12

Week 48

Mean (SD)
0.86 (0.574)
0.95 (0.715)
1.19 (0.777)
1.08 (0.736)

Median
0.87
0.73
1.25
0.95

Body Weight Quartiles (kg)

≤15.60
>15.60 to ≤18.60
>18.60 to ≤21.90
>21.90

Week 12

Mean (SD)
1.09 (0.723)
1.09 (0.622)
1.54 (0.649)
0.90 (0.642)

Median
1.13
1.09
1.49
0.83

Week 16

Mean (SD)
0.99 (0.622)
1.07 (0.739)
1.60 (0.845)
0.99 (0.806)

Median
0.90
1.12
1.76
0.89

Week 24

Mean (SD)
0.91 (0.799)
1.38 (0.780)
1.52 (1.243)
1.05 (0.844)

Median
0.61
1.37
1.42
1.00

Week 48

Mean (SD)
0.74 (0.468)
1.22 (0.852)
1.59 (0.498)
0.94 (0.789)

Median
0.75
1.10
1.55
0.81

Conclusion:

Treatment with 30 mg/m2 SC golimumab q4w + MTX resulted in sustained steady‐state trough serum golimumab concentrations over time. The PK/efficacy correlation analyses demonstrated that the BSA‐adjusted dosing regimen of 30 mg/m2 SC golimumab q4w provided adequate drug exposure for the desired efficacy.