Jeffrey S Hyams1, Daphne Chan, Omoniyi J Adedokun, Lakshmi Padgett, Dan Turner, Anne Griffiths, Genevieve Veereman, Melvin B Heyman, Joel R Rosh, Ghassan Wahbeh, Richard Strauss. 1. *Division of Gastroenterology, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut;†Janssen Research & Development, LLC, Springhouse, Pennsylvania;‡The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel;§IBD Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada;‖Pediatric Gastroenterology and Nutrition, University Hospital Brussels, Free University Brussels, Bruxelles, Belgium;¶Department of Pediatrics, University of California, San Francisco, California;**Pediatric Gastroenterology, Clinical Development and Research Affairs, Goryeb Children's Hospital/Atlantic Health, Morristown, New Jersey; and††Department of Pediatrics, Division of Gastroenterology, Seattle Children's Hospital, University of Washington, Seattle, Washington.
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 Median (interquartile range) serum golimumab concentrations were comparable to a historical reference adult UC population at weeks 2 (5.72 [3.80-9.17] μg/mL), 4 (7.61 [3.22-9.51] μg/mL), and 6 (2.64 [0.92-3.83] μg/mL).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.
BACKGROUND: Current treatments for pediatric ulcerative colitis (UC) are limited. We evaluated the pharmacokinetics and clinical benefits of subcutaneous golimumab, an anti-tumornecrosis 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-tumornecrosis 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.
Authors: Judith Pichler; Nima Memaran; Wolf Dietrich Huber; Christoph Aufricht; Bettina Bidmon-Fliegenschnee Journal: Acta Paediatr Date: 2020-09-30 Impact factor: 2.299
Authors: Joel R Rosh; Dan Turner; Anne Griffiths; Stanley A Cohen; Douglas Jacobstein; Omoniyi J Adedokun; Lakshmi Padgett; Natalie A Terry; Christopher O'Brien; Jeffrey S Hyams Journal: J Crohns Colitis Date: 2021-11-08 Impact factor: 9.071