title: Therapeutic Drug Monitoring of Golimumab in the Treatment of Ulcerative Colitis.
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.
authors.affiliation: Department of Medicine, University of California San Diego, 9500 Gilman Drive #0956, La Jolla, California, 92093, USA. nvandecasteele@ucsd.edu.|Robarts Clinical Trials Inc., Robarts Research Institute, London, Ontario, Canada. nvandecasteele@ucsd.edu.
authors.forename: Niels
authors.identifier: http://orcid.org/0000-0003-0854-0274
authors.initials: N
authors.lastname: Vande Casteele
authors.affiliation: Robarts Clinical Trials Inc., Robarts Research Institute, London, Ontario, Canada.|Department of Medicine, University of Western Ontario, London, Ontario, Canada.
authors.forename: Reena
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab; D000069285:Infliximab; D000068879:Adalimumab
keywords: anti drug antibodies; anti-TNF; immunogenicity; inflammatory bowel disease; pharmacokinetics