Subcutaneous Golimumab in Pediatric Ulcerative Colitis: Pharmacokinetics and Clinical Benefit

Inflamm Bowel Dis. 2017 Dec;23(12):2227-2237. doi: 10.1097/MIB.0000000000001262.

Abstract

Background: Current treatments for pediatric ulcerative colitis (UC) are limited. We evaluated the pharmacokinetics and clinical benefits of subcutaneous golimumab, an anti-tumor necrosis factor agent, in moderately-to-severely active pediatric patients with UC refractory to conventional therapy.

Methods: We report a multicenter, open-label study of golimumab with a pharmacokinetics phase (week 0-14). Patients had moderately-to-severely active UC and were naive to anti-tumor necrosis factor treatment. At weeks 0 and 2, patients received golimumab induction dosed by weight (<45 kg [90/45 mg/m]; ≥45 kg [200/100 mg]). Week 6 clinical responders continued golimumab q4w. Serum golimumab concentrations, clinical outcomes (Mayo score, PUCAI score), and adverse events are reported.

Results: Thirty-five patients (71.4% pancolitis) aged 6 to 17 years had baseline median (interquartile range), age, weight, and disease duration of 15.0 (11.0-16.0) years, 50.6 (35.2-59.0) kg, and 1.2 (0.6-3.1) years, respectively. Baseline Mayo and PUCAI scores were 8.0 (6.0-9.0) and 45 (35.0-65.0), respectively. Median (interquartile range) serum golimumab concentrations were comparable to a historical reference adult UC population at weeks 2 (5.72 [3.80-9.17] μg/mL), 4 (7.61 [3.22-9.51] μg/mL), and 6 (2.64 [0.92-3.83] μg/mL). Serum golimumab concentrations were generally lower in the <45 kg than ≥45 kg weight subgroup. At week 6, 60%, 34%, and 54%, of patients achieved Mayo clinical response, PUCAI clinical remission, and mucosal healing (Mayo subscore 0/1). No clinically important safety concerns were reported.

Conclusions: This open-label study demonstrates that pediatric and adult golimumab pharmacokinetics are similar. Clinical benefit and safety shows promise in biologically naive pediatric patients with UC.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / therapeutic use*
  • Child
  • Child, Preschool
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / immunology
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Subcutaneous
  • Male
  • Remission Induction
  • Tissue Distribution
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • golimumab

Supplementary concepts

  • Pediatric ulcerative colitis