title: Variability in Golimumab Exposure: A 'Real-Life' Observational Study in Active Ulcerative Colitis.
abstract: OBJECTIVE
  Golimumab has been approved recently to treat refractory moderate-to-severe ulcerative colitis [UC]. To date it is not clear why a considerable fraction of patients do not respond, or lose initial response, to golimumab therapy. Our aim was to investigate whether a low golimumab serum concentration and/or a positive anti-golimumab antibody status reduces the efficacy of this drug in patients with UC.
  
  
  METHODS
  Serum samples of 21 patients with moderate-to-severe UC were collected during the first 14 weeks of golimumab therapy. For measurement of golimumab serum concentrations, both a tumour necrosis factor [TNF]-coated enzyme-linked immunosorbent assay [ELISA] and a sandwich-type ELISA were developed. Anti-golimumab antibodies were measured using a bridging ELISA and a newly-developed drug-tolerant immunoassay. Clinical response and mucosal healing were assessed 14 weeks after start of treatment.
  
  
  RESULTS
  Out of 21 patients, 10 [48%] reached partial clinical response at Week 14. Median [interquartile range] serum golimumab concentration was significantly higher in partial clinical responders than in non-responders: 10.0 [7.8-10.5] µg/ml versus 7.4 [4.8-8.3] µg/ml at Week 2 [p = 0.035] and 5.1 [4.0-7.9] µg/ml versus 2.1 [1.8-4.2] µg/ml at week 6 [p = 0.037]. Four out of 21 UC patients developed anti-golimumab antibodies, detectable only using a drug-tolerant immunoassay, and three had a partial clinical response at that time. Clinical non-responders had a significantly more severe colitis, indicated by a higher endoscopic Mayo score at baseline compared with partial clinical responders [p = 0.048].
  
  
  CONCLUSIONS
  Adequate exposure to golimumab drives clinical response. A worse disease at baseline influences clinical response rate negatively.
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven, Leuven, Belgium.
authors.forename: Iris
authors.initials: I
authors.lastname: Detrez
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven, Leuven, Belgium.
authors.forename: Erwin
authors.initials: E
authors.lastname: Dreesen
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Van Stappen
authors.affiliation: Sanquin Diagnostic Services, Biologicals Laboratory, Amsterdam, The Netherlands.
authors.forename: Annick
authors.initials: A
authors.lastname: de Vries
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven, Leuven, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Brouwers
authors.affiliation: Department of Gastroenterology, Translational Research in Gastrointestinal Disorders, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.affiliation: Department of Gastroenterology, Translational Research in Gastrointestinal Disorders, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Department of Gastroenterology, Translational Research in Gastrointestinal Disorders, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven, Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Gils
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004361:Drug Tolerance / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; C529000:golimumab
keywords: Therapeutic drug monitoring; golimumab; ulcerative colitis