• Omoniyi J Adedokun, Zhenhua Xu, Sam Liao, Richard Strauss, Walter Reinisch, Brian G Feagan, and William J Sandborn.
• Janssen Research and Development, LLC, Spring House, PA, USA. Electronic address: oadedoku@its.jnj.com.
• Clin Ther. 2020 Jan 1; 42 (1): 157-174.e4.

PurposeGolimumab is a fully human monoclonal antibody to tumor necrosis factor-α and is indicated for the treatment of moderately to severely active ulcerative colitis (UC). This study analyzed the population pharmacokinetic (PK) properties of golimumab and exposure-response for efficacy and safety, using data from combined Phase II/III UC studies.MethodsData on serum golimumab concentration following IV and subcutaneous (SC) administration were fitted simultaneously using nonlinear mixed-effects modeling for the development of a population PK model. Logistic regression models were used for assessing relationships between serum golimumab concentrations and clinical efficacy outcomes in SC induction and maintenance studies. The percentages of patients developing infections, serious infections, and serious adverse events were assessed by golimumab exposure metric quartiles.FindingsThe PK properties of golimumab are well described by a 2-compartment model with first-order absorption and elimination. Typical values of PK parameters in a 70-kg patient were clearance, 0.544 L/d; central and peripheral compartment Vd, 3.43 and 2.27 L, respectively; and intercompartmental clearance, 0.291 L/d. Golimumab t1/2 was 10.5 days; bioavailability following SC administration was 52.2%. Body weight, anti-golimumab antibodies, serum albumin, C-reactive protein, and alkaline phosphatase affected golimumab disposition. A positive exposure-response relationship was established between golimumab concentration and efficacy outcomes. No apparent correlation between golimumab exposure and rate of infections, serious infections, or serious adverse events was observed in patients receiving golimumab 50 or 100 mg SC every 4 weeks through 1 year.ImplicationsBody weight, serum albumin, and anti-golimumab antibodies explain some of the variability observed in the PK properties of golimumab, and exposure-response findings support the recommended posology of golimumab in UC. ClinicalTrials.gov identifiers: NCT00488774, NCT00487539, and NCT00488631.Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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