Subcutaneous Golimumab in Pediatric Ulcerative Colitis: Pharmacokinetics and Clinical Benefit

Jeffrey S. Hyams, Daphne Chan, Omoniyi J. Adedokun, Lakshmi Padgett, Dan Turner, Anne Griffiths, Genevieve Veereman, Melvin B. Heyman, Joel R. Rosh, Ghassan Wahbeh, Richard Strauss

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 Median (interquartile range) serum golimumab concentrations were comparable to a historical reference adult UC population at weeks 2 (5.72 [3.80-9.17] μg/mL), 4 (7.61 [3.22-9.51] μg/mL), and 6 (2.64 [0.92-3.83] μg/mL).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.

Original languageEnglish (US)
Pages (from-to)2227-2237
Number of pages11
JournalInflammatory bowel diseases
Volume23
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Pharmacokinetics
Ulcerative Colitis
Pediatrics
Weights and Measures
Tumor Necrosis Factor-alpha
Serum
Safety
golimumab
Pediatric ulcerative colitis
Therapeutics
Population

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Hyams, J. S., Chan, D., Adedokun, O. J., Padgett, L., Turner, D., Griffiths, A., ... Strauss, R. (2017). Subcutaneous Golimumab in Pediatric Ulcerative Colitis: Pharmacokinetics and Clinical Benefit. Inflammatory bowel diseases, 23(12), 2227-2237. https://doi.org/10.1097/MIB.0000000000001262
Hyams, Jeffrey S. ; Chan, Daphne ; Adedokun, Omoniyi J. ; Padgett, Lakshmi ; Turner, Dan ; Griffiths, Anne ; Veereman, Genevieve ; Heyman, Melvin B. ; Rosh, Joel R. ; Wahbeh, Ghassan ; Strauss, Richard. / Subcutaneous Golimumab in Pediatric Ulcerative Colitis : Pharmacokinetics and Clinical Benefit. In: Inflammatory bowel diseases. 2017 ; Vol. 23, No. 12. pp. 2227-2237.
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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.",
author = "Hyams, {Jeffrey S.} and Daphne Chan and Adedokun, {Omoniyi J.} and Lakshmi Padgett and Dan Turner and Anne Griffiths and Genevieve Veereman and Heyman, {Melvin B.} and Rosh, {Joel R.} and Ghassan Wahbeh and Richard Strauss",
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Hyams, JS, Chan, D, Adedokun, OJ, Padgett, L, Turner, D, Griffiths, A, Veereman, G, Heyman, MB, Rosh, JR, Wahbeh, G & Strauss, R 2017, 'Subcutaneous Golimumab in Pediatric Ulcerative Colitis: Pharmacokinetics and Clinical Benefit', Inflammatory bowel diseases, vol. 23, no. 12, pp. 2227-2237. https://doi.org/10.1097/MIB.0000000000001262

Subcutaneous Golimumab in Pediatric Ulcerative Colitis : Pharmacokinetics and Clinical Benefit. / Hyams, Jeffrey S.; Chan, Daphne; Adedokun, Omoniyi J.; Padgett, Lakshmi; Turner, Dan; Griffiths, Anne; Veereman, Genevieve; Heyman, Melvin B.; Rosh, Joel R.; Wahbeh, Ghassan; Strauss, Richard.

In: Inflammatory bowel diseases, Vol. 23, No. 12, 01.12.2017, p. 2227-2237.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Subcutaneous Golimumab in Pediatric Ulcerative Colitis

T2 - Pharmacokinetics and Clinical Benefit

AU - Hyams, Jeffrey S.

AU - Chan, Daphne

AU - Adedokun, Omoniyi J.

AU - Padgett, Lakshmi

AU - Turner, Dan

AU - Griffiths, Anne

AU - Veereman, Genevieve

AU - Heyman, Melvin B.

AU - Rosh, Joel R.

AU - Wahbeh, Ghassan

AU - Strauss, Richard

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

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