Population Pharmacokinetic and Exposure-Response Model Simulations: Predicted Exposure and Efficacy for Maintenance Doses of Intravenous Golimumab Every 6 or 8 Weeks in Patients With Moderately to Severely Active Rheumatoid Arthritis

被引：1

作者：

Lee, Jong Bong ^{[1
,6
]}

Broadwell, Aaron ^{[2
]}

Fan, Yijun ^{[3
]}

Hu, Chuanpu ^{[1
]}

Adedokun, Omoniyi J. ^{[1
]}

Chakravarty, Soumya D. ^{[4
,5
]}

Zhou, Honghui ^{[1
]}

Xu, Zhenhua ^{[1
]}

Leu, Jocelyn H. ^{[1
]}

机构：

[1] Janssen Res & Dev LLC, 1400 McKean R, Spring House, PA 19477 USA

[2] Rheumatol & Osteoporosis Specialists, Shreveport, LA USA

[3] TMSA Rheumatol, Dallas, TX USA

[4] Janssen Sci Affairs LLC, Philadelphia, PA USA

[5] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA

[6] Novartis Inst BioMed Res, E Hanover, NJ USA

来源：

CLINICAL THERAPEUTICS | 2022年 / 44卷 / 03期

关键词：

dosing regimen; intravenous golimumab; rheumatoid arthritis; simulation; METHOTREXATE THERAPY; DOUBLE-BLIND; RADIOGRAPHIC BENEFIT; OPEN-LABEL; MULTICENTER; IMPROVEMENT; PHASE-3; SAFETY;

D O I：

10.1016/j.clinthera.2022.01.015

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Purpose: Golimumab is approved to treat moderateto-severe active rheumatoid arthritis when given intravenously at weeks 0 and 4, then every 8 weeks (Q8W) with concomitant methotrexate. These analyses assessed whether a shorter dosing interval could ameliorate diminished efficacy experienced by a small proportion of patients toward the end of the dosing interval. Methods: Population pharmacokinetic and exposure-response modeling simulations were performed for intravenous golimumab 2 mg/kg at weeks 0 and 4, then Q8W or every 6 weeks (Q6W) through 1 year. A 2-compartment pharmacokinetic model with linear clearance developed based on GO-FURTHER (A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNF alpha Monoclonal Antibody, Administered Intravenously, in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy) study data was used for pharmacokinetic simulations. A latent-variable indirect exposure-response model developed based on GO-FURTHER American College of Rheumatology (ACR) 20%/50%/70% improvement (ACR20, ACR50, and ACR70, respectively) data was used to predict clinical endpoints of ACR20/ACR50/ACR70 response rates. Findings: For Q6W and Q8W dosing, respectively, predicted median golimumab steady-state trough (C-trough,C-ss) concentrations were 0.57 and 0.24 mu g/mL, and C-max at steady state values were 33.1 and 32.9 mu g/mL. Predicted peak median ACR20 steady-state response rates were 76.7% (Q6W) and 75.6% (Q8W). Predicted median ACR20 response rates at C-trough,C-ss increased by 4.7 percentage points with Q6W (73.7%) versus Q8W (69.0%) dosing. Greater improvement in ACR20 response rates at trough time points was predicted in patients with lower golimumab trough serum concentrations. Consistent findings were observed for ACR50/ACR70 response rates. (C) 2022 Published by Elsevier Inc.

引用

页码：457 / +

页数：10