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Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis
OBJECTIVES: To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA). METHODS: In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJI...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487273/ https://www.ncbi.nlm.nih.gov/pubmed/33506875 http://dx.doi.org/10.1093/rheumatology/keab047 |
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author | Ruperto, Nicolino Brunner, Hermine I Ramanan, Athimalaipet V Horneff, Gerd Cuttica, Rubén Henrickson, Michael Anton, Jordi Boteanu, Alina Lucica Penades, Inmaculada Calvo Minden, Kirsten Schmeling, Heinrike Hufnagel, Markus Weiss, Jennifer E Pardeo, Manuela Nanda, Kabita Roth, Johannes Rubio-Pérez, Nadina Hsu, Joy C Wimalasundera, Sunethra Wells, Chris Bharucha, Kamal Douglass, Wendy Bao, Min Mallalieu, Navita L Martini, Alberto Lovell, Daniel Benedetti, Fabrizio De |
author_facet | Ruperto, Nicolino Brunner, Hermine I Ramanan, Athimalaipet V Horneff, Gerd Cuttica, Rubén Henrickson, Michael Anton, Jordi Boteanu, Alina Lucica Penades, Inmaculada Calvo Minden, Kirsten Schmeling, Heinrike Hufnagel, Markus Weiss, Jennifer E Pardeo, Manuela Nanda, Kabita Roth, Johannes Rubio-Pérez, Nadina Hsu, Joy C Wimalasundera, Sunethra Wells, Chris Bharucha, Kamal Douglass, Wendy Bao, Min Mallalieu, Navita L Martini, Alberto Lovell, Daniel Benedetti, Fabrizio De |
author_sort | Ruperto, Nicolino |
collection | PubMed |
description | OBJECTIVES: To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA). METHODS: In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or <30 kg, respectively. Primary end points were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with i.v. tocilizumab (i.v.-TCZ) in sJIA and pJIA. RESULTS: Study participants were 51 sJIA patients and 52 pJIA patients aged 1–17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (C(trough)) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ. CONCLUSION: s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904292 and NCT01904279 |
format | Online Article Text |
id | pubmed-8487273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-84872732021-10-04 Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis Ruperto, Nicolino Brunner, Hermine I Ramanan, Athimalaipet V Horneff, Gerd Cuttica, Rubén Henrickson, Michael Anton, Jordi Boteanu, Alina Lucica Penades, Inmaculada Calvo Minden, Kirsten Schmeling, Heinrike Hufnagel, Markus Weiss, Jennifer E Pardeo, Manuela Nanda, Kabita Roth, Johannes Rubio-Pérez, Nadina Hsu, Joy C Wimalasundera, Sunethra Wells, Chris Bharucha, Kamal Douglass, Wendy Bao, Min Mallalieu, Navita L Martini, Alberto Lovell, Daniel Benedetti, Fabrizio De Rheumatology (Oxford) Clinical Science OBJECTIVES: To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA). METHODS: In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or <30 kg, respectively. Primary end points were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with i.v. tocilizumab (i.v.-TCZ) in sJIA and pJIA. RESULTS: Study participants were 51 sJIA patients and 52 pJIA patients aged 1–17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (C(trough)) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ. CONCLUSION: s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904292 and NCT01904279 Oxford University Press 2021-01-28 /pmc/articles/PMC8487273/ /pubmed/33506875 http://dx.doi.org/10.1093/rheumatology/keab047 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, [br]distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Clinical Science Ruperto, Nicolino Brunner, Hermine I Ramanan, Athimalaipet V Horneff, Gerd Cuttica, Rubén Henrickson, Michael Anton, Jordi Boteanu, Alina Lucica Penades, Inmaculada Calvo Minden, Kirsten Schmeling, Heinrike Hufnagel, Markus Weiss, Jennifer E Pardeo, Manuela Nanda, Kabita Roth, Johannes Rubio-Pérez, Nadina Hsu, Joy C Wimalasundera, Sunethra Wells, Chris Bharucha, Kamal Douglass, Wendy Bao, Min Mallalieu, Navita L Martini, Alberto Lovell, Daniel Benedetti, Fabrizio De Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis |
title | Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis |
title_full | Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis |
title_fullStr | Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis |
title_full_unstemmed | Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis |
title_short | Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis |
title_sort | subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis |
topic | Clinical Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487273/ https://www.ncbi.nlm.nih.gov/pubmed/33506875 http://dx.doi.org/10.1093/rheumatology/keab047 |
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