title: Pharmacokinetics and Exposure-response Relationship of Golimumab in Patients with Moderately-to-Severely Active Ulcerative Colitis: Results from Phase 2/3 PURSUIT Induction and Maintenance Studies.
abstract: OBJECTIVE
  To assess golimumab pharmacokinetics [PK] and exposure-response [ER] in adults with moderate-to-severe ulcerative colitis [UC] from the Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment [PURSUIT] studies.
  
  
  METHODS
  We analysed golimumab PK and ER data of patients with moderate-to-severe UC from the PURSUIT-subcutaneous induction [N = 1064] and maintenance [N = 464] studies. Induction analyses evaluated serum golimumab concentration [SGC] and efficacy data through Week [wk] 6 following subcutaneous doses at wk0 and wk2; maintenance analyses assessed data through wk54 following 4-weekly dosing. ER relationships were assessed using trend, logistic regression, and receiver-operating-characteristic curve analyses.
  
  
  RESULTS
  Median SGCs peaked at induction wk2 for golimumab 100/50mg, 200/100mg, and 400/200mg. Wk6 median SGCs were 0.78, 1.78, and 4.01 μg/ml, respectively. SGCs were sustained, reaching steady state approximately 8wks after golimumab maintenance commenced [wk14 of golimumab] regardless of induction dose. Median trough SGCs from maintenance wks8-44 ranged from 0.69 to 0.83 µg/ml [50 mg] and 1.33-1.58 µg/ml [100 mg]. SGCs were approximately dose proportional, and higher SGCs were associated with higher efficacy response rates during induction and maintenance. Factors associated with golimumab exposure were body weight, antibody-to-golimumab status, serum albumin, alkaline phosphatase, faecal markers, C-reactive protein, and pancolitis. SGCs of 2.5 µg/ml [induction wk6] and 1.4 µg/ml [maintenance steady-state trough] are potential target concentrations. Immunomodulators had no apparent impact on SGC with golimumab 100mg, whereas drug levels were slightly higher with golimumab 50mg with vs without immunomodulators.
  
  
  CONCLUSIONS
  SGCs are approximately dose proportional, and a positive SGC-efficacy relationship exists during induction/maintenance golimumab treatment of adult UC patients. Optimal SGC targets require validation in prospective studies.
authors.affiliation: Department of Global Clinical Pharmacology, Janssen Research & Development, LLC, Spring House, PA, USA OAdedoku@its.jnj.com.
authors.forename: Omoniyi J
authors.initials: OJ
authors.lastname: Adedokun
authors.affiliation: Department of Global Clinical Pharmacology, Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Clinical Development Immunology, Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Colleen W
authors.initials: CW
authors.lastname: Marano
authors.affiliation: Department of Translational Medicine Sciences, Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Strauss
authors.affiliation: Department of Global Clinical Pharmacology, Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Clinical Biostatistics, Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Jewel
authors.initials: J
authors.lastname: Johanns
authors.affiliation: Department of Global Clinical Pharmacology, Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Honghui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Biologics Development Sciences, Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Hugh M
authors.initials: HM
authors.lastname: Davis
authors.affiliation: Department of Gastroenterology, Universitätsklinik für Innere Medizin III, Vienna, Austria & McMaster University, Hamilton, ON, Canada.
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.affiliation: Department of Gastroenterology, Robarts Research Institute, University of Western Ontario, London, ON, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Department of Gastroenterology, Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: Department of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab
keywords: Ulcerative colitis; anti-tumour necrosis factor; pharmacokinetics