Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trial
Abstract Background The anti–interleukin-6 receptor-alpha antibody tocilizumab was approved for intravenous (IV) injection in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) aged 2 to 17 years based on results of a randomized controlled phase 3 trial. Tocilizumab treatme...
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2019-08-01
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Series: | Pediatric Rheumatology Online Journal |
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Online Access: | http://link.springer.com/article/10.1186/s12969-019-0364-z |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Navita L. Mallalieu Sunethra Wimalasundera Joy C. Hsu Wendy Douglass Chris Wells Inmaculada Calvo Penades Ruben Cuttica Hans-Iko Huppertz Rik Joos Yukiko Kimura Diana Milojevic Margalit Rosenkranz Kenneth Schikler Tamas Constantin Carine Wouters |
spellingShingle |
Navita L. Mallalieu Sunethra Wimalasundera Joy C. Hsu Wendy Douglass Chris Wells Inmaculada Calvo Penades Ruben Cuttica Hans-Iko Huppertz Rik Joos Yukiko Kimura Diana Milojevic Margalit Rosenkranz Kenneth Schikler Tamas Constantin Carine Wouters Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trial Pediatric Rheumatology Online Journal Biological therapy Inflammation Juvenile idiopathic arthritis Pharmacokinetics |
author_facet |
Navita L. Mallalieu Sunethra Wimalasundera Joy C. Hsu Wendy Douglass Chris Wells Inmaculada Calvo Penades Ruben Cuttica Hans-Iko Huppertz Rik Joos Yukiko Kimura Diana Milojevic Margalit Rosenkranz Kenneth Schikler Tamas Constantin Carine Wouters |
author_sort |
Navita L. Mallalieu |
title |
Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trial |
title_short |
Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trial |
title_full |
Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trial |
title_fullStr |
Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trial |
title_full_unstemmed |
Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trial |
title_sort |
intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trial |
publisher |
BMC |
series |
Pediatric Rheumatology Online Journal |
issn |
1546-0096 |
publishDate |
2019-08-01 |
description |
Abstract Background The anti–interleukin-6 receptor-alpha antibody tocilizumab was approved for intravenous (IV) injection in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) aged 2 to 17 years based on results of a randomized controlled phase 3 trial. Tocilizumab treatment in systemic juvenile idiopathic arthritis (sJIA) patients younger than 2 was investigated in this open-label phase 1 trial and compared with data from the previous trial in patients aged 2 to 17 years. Methods Patients younger than 2 received open-label tocilizumab 12 mg/kg IV every 2 weeks (Q2W) during a 12-week main evaluation period and an optional extension period. The primary end point was comparability of pharmacokinetics during the main evaluation period to that of the previous trial (in patients aged 2–17 years), and the secondary end point was safety; pharmacodynamics and efficacy end points were exploratory. Descriptive comparisons for pharmacokinetics, pharmacodynamics, safety, and efficacy were made with sJIA patients aged 2 to 17 years weighing < 30 kg (n = 38) who received tocilizumab 12 mg/kg IV Q2W in the previous trial (control group). Results Eleven patients (mean age, 1.3 years) received tocilizumab during the main evaluation period. The primary end point was met: tocilizumab exposures for patients younger than 2 were within the range of the control group (mean [±SD] μg/mL concentration at the end-of-dosing interval [Cmin]: 39.8 [±14.3] vs 57.5 [±23.3]; maximum concentration [Cmax] postdose: 288 [±40.4] vs 245 [±57.2]). At week 12, pharmacodynamic measures were similar between patients younger than 2 and the control group; mean change from baseline in Juvenile Arthritis Disease Activity Score-71 was − 17.4 in patients younger than 2 and − 28.8 in the control group; rash was reported by 14.3 and 13.5% of patients, respectively. Safety was comparable except for the incidence of serious hypersensitivity reactions (27.3% in patients younger than 2 vs 2.6% in the control group). Conclusions Tocilizumab 12 mg/kg IV Q2W provided pharmacokinetics, pharmacodynamics, and efficacy in sJIA patients younger than 2 comparable to those in patients aged 2 to 17 years. Safety was comparable except for a higher incidence of serious hypersensitivity events in patients younger than 2 years. Classification Juvenile idiopathic arthritis. Trial registration ClinicalTrials.gov, NCT01455701. Registered, October 20, 2011, Date of enrollment of first participant: October 26, 2012. |
topic |
Biological therapy Inflammation Juvenile idiopathic arthritis Pharmacokinetics |
url |
http://link.springer.com/article/10.1186/s12969-019-0364-z |
work_keys_str_mv |
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doaj-7f02982439724267a0d9a1e6ca5fa34f2020-11-25T03:39:58ZengBMCPediatric Rheumatology Online Journal1546-00962019-08-0117111010.1186/s12969-019-0364-zIntravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trialNavita L. Mallalieu0Sunethra Wimalasundera1Joy C. Hsu2Wendy Douglass3Chris Wells4Inmaculada Calvo Penades5Ruben Cuttica6Hans-Iko Huppertz7Rik Joos8Yukiko Kimura9Diana Milojevic10Margalit Rosenkranz11Kenneth Schikler12Tamas Constantin13Carine Wouters14Roche Innovation CenterRoche Products Ltd.Roche Innovation CenterRoche Products Ltd.Roche Products Ltd.Unidad de Reumatología Pediátrica, Hospital Universitario y Politécnico La FeSección Reumatologia, Hospital General de Niños Pedro de ElizaldeCenter for Paediatrics and Youth Medicine, Professor Hess Children’s HospitalDepartment of RheumatologyDivision of Pediatric Rheumatology, Joseph M. Sanzari Children’s Hospital, Hackensack University Medical CenterPediatric Rheumatology, Johns Hopkins All Children’s Department of MedicineDivision of Pediatric Rheumatology, UPMC Children’s Hospital of PittsburghDepartment of Pediatrics, University of Louisville Medical SchoolDepartment of Pediatrics, Semmelweis UniversityDepartment of Microbiology and Immunology, Laboratory Immunobiology and University Hospitals Leuven, Pediatric Rheumatology, Katholieke Universiteit Leuven, University of LeuvenAbstract Background The anti–interleukin-6 receptor-alpha antibody tocilizumab was approved for intravenous (IV) injection in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) aged 2 to 17 years based on results of a randomized controlled phase 3 trial. Tocilizumab treatment in systemic juvenile idiopathic arthritis (sJIA) patients younger than 2 was investigated in this open-label phase 1 trial and compared with data from the previous trial in patients aged 2 to 17 years. Methods Patients younger than 2 received open-label tocilizumab 12 mg/kg IV every 2 weeks (Q2W) during a 12-week main evaluation period and an optional extension period. The primary end point was comparability of pharmacokinetics during the main evaluation period to that of the previous trial (in patients aged 2–17 years), and the secondary end point was safety; pharmacodynamics and efficacy end points were exploratory. Descriptive comparisons for pharmacokinetics, pharmacodynamics, safety, and efficacy were made with sJIA patients aged 2 to 17 years weighing < 30 kg (n = 38) who received tocilizumab 12 mg/kg IV Q2W in the previous trial (control group). Results Eleven patients (mean age, 1.3 years) received tocilizumab during the main evaluation period. The primary end point was met: tocilizumab exposures for patients younger than 2 were within the range of the control group (mean [±SD] μg/mL concentration at the end-of-dosing interval [Cmin]: 39.8 [±14.3] vs 57.5 [±23.3]; maximum concentration [Cmax] postdose: 288 [±40.4] vs 245 [±57.2]). At week 12, pharmacodynamic measures were similar between patients younger than 2 and the control group; mean change from baseline in Juvenile Arthritis Disease Activity Score-71 was − 17.4 in patients younger than 2 and − 28.8 in the control group; rash was reported by 14.3 and 13.5% of patients, respectively. Safety was comparable except for the incidence of serious hypersensitivity reactions (27.3% in patients younger than 2 vs 2.6% in the control group). Conclusions Tocilizumab 12 mg/kg IV Q2W provided pharmacokinetics, pharmacodynamics, and efficacy in sJIA patients younger than 2 comparable to those in patients aged 2 to 17 years. Safety was comparable except for a higher incidence of serious hypersensitivity events in patients younger than 2 years. Classification Juvenile idiopathic arthritis. Trial registration ClinicalTrials.gov, NCT01455701. Registered, October 20, 2011, Date of enrollment of first participant: October 26, 2012.http://link.springer.com/article/10.1186/s12969-019-0364-zBiological therapyInflammationJuvenile idiopathic arthritisPharmacokinetics |