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Pharmaceutical Research

, Volume 34, Issue 8, pp 1556–1563 | Cite as

Therapeutic Drug Monitoring of Golimumab in the Treatment of Ulcerative Colitis

Expert Review

Abstract

Ulcerative colitis (UC) is a relapsing-remitting chronic inflammatory disorder affecting the mucosal surface in a continuous manner from the rectum through part of, or the entire, colon. Patients with severe disease and those who become refractory or intolerant to corticosteroids and/or immunosuppressants, require treatment with biologic agents that target tumor necrosis factor-α (TNF). Golimumab, a fully human monoclonal antibody, is the latest TNF antagonist to get approved for the treatment of moderate-to-severe UC. Subcutaneously administered golimumab induces and maintains clinical response, remission, and mucosal healing. Serum concentrations of golimumab are associated with response to therapy, as patients with higher drug exposure are more likely to achieve these outcomes. Since various patient and disease-related factors were shown to influence the pharmacokinetics of TNF antagonists, drug exposure may be variable over time and between patients, affecting success of therapy. A major contributing factor is immunogenicity, with development of anti-drug antibodies (ADAb) and an accelerated clearance of drug as a result. Although there is a growing body of evidence to support therapeutic drug monitoring (TDM) for infliximab and adalimumab, two other TNF antagonists, only limited data is available for golimumab. In addition, the clinically important drug exposure thresholds are not widely known, which has limited the use of TDM for golimumab in clinical practice. This review summarizes available data regarding the use of golimumab for UC, with emphasis on the pharmacokinetics, exposure-response relationship, and the role of TDM in optimizing therapy.

Key Words

anti drug antibodies anti-TNF immunogenicity inflammatory bowel disease pharmacokinetics 

Abbreviations

ADAb

Anti-drug-antibody

CRP

C-reactive protein

ELISA

Enzyme-linked immune-sorbent assay

HMSA

Homogenous mobility shift assay

HPLC

High pressure liquid chromatography

IBD

Inflammatory bowel disease

IV

Intravenous

PK

Pharmacokinetics

RES

Reticuloendothelial system

RIA

Radio-immunoassay

ROC

Receiver operating characteristic

SC

Subcutaneous

TDM

Therapeutic drug monitoring

TMDD

Target mediated drug disposition

TNF

Tumor necrosis factor-α

UC

Ulcerative colitis

VNTR

Variable number tandem repeat

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of MedicineUniversity of California San DiegoCaliforniaUSA
  2. 2.Robarts Clinical Trials Inc.Robarts Research InstituteLondonCanada
  3. 3.Department of MedicineUniversity of Western OntarioLondonCanada

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