Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1093/rheumatology/keab021 http://hdl.handle.net/11449/229170 |
Resumo: | Objectives: To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA). Methods: Children aged 2 to <18 years with active pc-JIA despite MTX therapy for ≥2 months received 80 mg/m2 golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed. Results: In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 μg/ml and 399 μg day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to i.v. golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock. Conclusion: Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA. ClinicalTrials.gov number NCT02277444 |
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Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritisGolimumabIntravenousJuvenile idiopathic arthritisPharmacokineticsTumour necrosis factor alphaObjectives: To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA). Methods: Children aged 2 to <18 years with active pc-JIA despite MTX therapy for ≥2 months received 80 mg/m2 golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed. Results: In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 μg/ml and 399 μg day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to i.v. golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock. Conclusion: Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA. ClinicalTrials.gov number NCT02277444IRCCS Istituto Giannina Gaslini Clinica Pediatrica e Reumatologia PRINTOCincinnati Children's Hospital Medical Center Division of Rheumatology University of CincinnatiFacultad de Medicina Universidad Autónoma de Chihuahua Circuito Universitario Campus IIPanorama Medical Centre Rheumatology Private PracticeCentro de Reumatología y Autoinmunidad (CREA) Hospital México Americano, JaliscoCentro Médico Privado de Reumatología Rheumatology Section, San Miguel de TucumanRandall Children's Hospital at Legacy EmanuelDepartment of Pediatrics Alberta Children's Hospital Cumming School of Medicine University of CalgaryDepartment of Pediatric Infectious Diseases and Immunology School of Medicine Pontificia Universidad Católica de ChileRheumatology Section Hospital Pedro de ElizaldePediatric Rheumatology University of UtahFederal State Budget Educational Institution of Higher Education Bashkir State Medical University Ministry of Healthcare of Russian FederationRed Cross War Memorial Children's Hospital Groote Schuur Hospital University of Cape TownPediatric Department Clinical Hospital No. 5Escola Paulista de Medicina Universidade Federal de São PauloInstituto CAICIHospital de Clínicas de Porto Alegre Universidade Federal Do Rio Grande Do sulPaediatric Department Hospital das Clinicas-Botucatu Medicine University UNESPHospital Infantil de México Federico Gómez Medicina Interna y ReumatologiaCincinnati Children's Hospital Medical CenterJanssen Research and Development LLCUniversità Degli Studi di Genova Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-InfantiliPaediatric Department Hospital das Clinicas-Botucatu Medicine University UNESPPRINTOUniversity of CincinnatiCircuito Universitario Campus IIRheumatology Private PracticeHospital México AmericanoRheumatology SectionRandall Children's Hospital at Legacy EmanuelUniversity of CalgaryPontificia Universidad Católica de ChileHospital Pedro de ElizaldeUniversity of UtahMinistry of Healthcare of Russian FederationUniversity of Cape TownClinical Hospital No. 5Universidade Federal de São Paulo (UNIFESP)Instituto CAICIUniversidade Federal Do Rio Grande Do sulUniversidade Estadual Paulista (UNESP)Medicina Interna y ReumatologiaCincinnati Children's Hospital Medical CenterLLCGenetica e Scienze Materno-InfantiliRuperto, NicolinoBrunner, Hermine IPacheco-Tena, CésarLouw, IngridVega-Cornejo, GabrielSpindler, Alberto JKingsbury, Daniel JSchmeling, HeinrikeBorzutzky, ArturoCuttica, RubénInman, C. J.Malievskiy, VictorScott, ChristiaanKeltsev, VladimirTerreri, Maria TeresaViola, Diego OscarXavier, Ricardo MFernandes, Taciana A. Pedrosa [UNESP]Velázquez, María Del Rocío MaldonadoHenrickson, MichaelClark, Michael BBensley, Karen ALi, XiaomingLo, Kim HungLeu, Jocelyn HHsu, Chyi-HungHsia, Elizabeth CXu, ZhenhuaMartini, AlbertoLovell, Daniel JAppenzeller, SimoneOliveira, SheilaSilva, Clóvis ArthurLevy, DeborahNavarrete, CarmenAviel, Yonatan ButbulUziel, YosefAlexeeva, EkaterinaChasnyk, VladimirSpivakovsky, YuryGottlieb, BethRabinovich, EglaZeft, AndrewGriffin, ThomasDe Ranieri, DeirdreCarrasco, Ruy2022-04-29T08:30:48Z2022-04-29T08:30:48Z2021-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article4495-4507http://dx.doi.org/10.1093/rheumatology/keab021Rheumatology (United Kingdom), v. 60, n. 10, p. 4495-4507, 2021.1462-03321462-0324http://hdl.handle.net/11449/22917010.1093/rheumatology/keab0212-s2.0-85110584854Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengRheumatology (United Kingdom)info:eu-repo/semantics/openAccess2022-04-29T08:30:49Zoai:repositorio.unesp.br:11449/229170Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-04-29T08:30:49Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis |
title |
Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis |
spellingShingle |
Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis Ruperto, Nicolino Golimumab Intravenous Juvenile idiopathic arthritis Pharmacokinetics Tumour necrosis factor alpha |
title_short |
Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis |
title_full |
Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis |
title_fullStr |
Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis |
title_full_unstemmed |
Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis |
title_sort |
Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis |
author |
Ruperto, Nicolino |
author_facet |
Ruperto, Nicolino Brunner, Hermine I Pacheco-Tena, César Louw, Ingrid Vega-Cornejo, Gabriel Spindler, Alberto J Kingsbury, Daniel J Schmeling, Heinrike Borzutzky, Arturo Cuttica, Rubén Inman, C. J. Malievskiy, Victor Scott, Christiaan Keltsev, Vladimir Terreri, Maria Teresa Viola, Diego Oscar Xavier, Ricardo M Fernandes, Taciana A. Pedrosa [UNESP] Velázquez, María Del Rocío Maldonado Henrickson, Michael Clark, Michael B Bensley, Karen A Li, Xiaoming Lo, Kim Hung Leu, Jocelyn H Hsu, Chyi-Hung Hsia, Elizabeth C Xu, Zhenhua Martini, Alberto Lovell, Daniel J Appenzeller, Simone Oliveira, Sheila Silva, Clóvis Arthur Levy, Deborah Navarrete, Carmen Aviel, Yonatan Butbul Uziel, Yosef Alexeeva, Ekaterina Chasnyk, Vladimir Spivakovsky, Yury Gottlieb, Beth Rabinovich, Egla Zeft, Andrew Griffin, Thomas De Ranieri, Deirdre Carrasco, Ruy |
author_role |
author |
author2 |
Brunner, Hermine I Pacheco-Tena, César Louw, Ingrid Vega-Cornejo, Gabriel Spindler, Alberto J Kingsbury, Daniel J Schmeling, Heinrike Borzutzky, Arturo Cuttica, Rubén Inman, C. J. Malievskiy, Victor Scott, Christiaan Keltsev, Vladimir Terreri, Maria Teresa Viola, Diego Oscar Xavier, Ricardo M Fernandes, Taciana A. Pedrosa [UNESP] Velázquez, María Del Rocío Maldonado Henrickson, Michael Clark, Michael B Bensley, Karen A Li, Xiaoming Lo, Kim Hung Leu, Jocelyn H Hsu, Chyi-Hung Hsia, Elizabeth C Xu, Zhenhua Martini, Alberto Lovell, Daniel J Appenzeller, Simone Oliveira, Sheila Silva, Clóvis Arthur Levy, Deborah Navarrete, Carmen Aviel, Yonatan Butbul Uziel, Yosef Alexeeva, Ekaterina Chasnyk, Vladimir Spivakovsky, Yury Gottlieb, Beth Rabinovich, Egla Zeft, Andrew Griffin, Thomas De Ranieri, Deirdre Carrasco, Ruy |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
PRINTO University of Cincinnati Circuito Universitario Campus II Rheumatology Private Practice Hospital México Americano Rheumatology Section Randall Children's Hospital at Legacy Emanuel University of Calgary Pontificia Universidad Católica de Chile Hospital Pedro de Elizalde University of Utah Ministry of Healthcare of Russian Federation University of Cape Town Clinical Hospital No. 5 Universidade Federal de São Paulo (UNIFESP) Instituto CAICI Universidade Federal Do Rio Grande Do sul Universidade Estadual Paulista (UNESP) Medicina Interna y Reumatologia Cincinnati Children's Hospital Medical Center LLC Genetica e Scienze Materno-Infantili |
dc.contributor.author.fl_str_mv |
Ruperto, Nicolino Brunner, Hermine I Pacheco-Tena, César Louw, Ingrid Vega-Cornejo, Gabriel Spindler, Alberto J Kingsbury, Daniel J Schmeling, Heinrike Borzutzky, Arturo Cuttica, Rubén Inman, C. J. Malievskiy, Victor Scott, Christiaan Keltsev, Vladimir Terreri, Maria Teresa Viola, Diego Oscar Xavier, Ricardo M Fernandes, Taciana A. Pedrosa [UNESP] Velázquez, María Del Rocío Maldonado Henrickson, Michael Clark, Michael B Bensley, Karen A Li, Xiaoming Lo, Kim Hung Leu, Jocelyn H Hsu, Chyi-Hung Hsia, Elizabeth C Xu, Zhenhua Martini, Alberto Lovell, Daniel J Appenzeller, Simone Oliveira, Sheila Silva, Clóvis Arthur Levy, Deborah Navarrete, Carmen Aviel, Yonatan Butbul Uziel, Yosef Alexeeva, Ekaterina Chasnyk, Vladimir Spivakovsky, Yury Gottlieb, Beth Rabinovich, Egla Zeft, Andrew Griffin, Thomas De Ranieri, Deirdre Carrasco, Ruy |
dc.subject.por.fl_str_mv |
Golimumab Intravenous Juvenile idiopathic arthritis Pharmacokinetics Tumour necrosis factor alpha |
topic |
Golimumab Intravenous Juvenile idiopathic arthritis Pharmacokinetics Tumour necrosis factor alpha |
description |
Objectives: To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA). Methods: Children aged 2 to <18 years with active pc-JIA despite MTX therapy for ≥2 months received 80 mg/m2 golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed. Results: In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 μg/ml and 399 μg day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to i.v. golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock. Conclusion: Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA. ClinicalTrials.gov number NCT02277444 |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-10-01 2022-04-29T08:30:48Z 2022-04-29T08:30:48Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1093/rheumatology/keab021 Rheumatology (United Kingdom), v. 60, n. 10, p. 4495-4507, 2021. 1462-0332 1462-0324 http://hdl.handle.net/11449/229170 10.1093/rheumatology/keab021 2-s2.0-85110584854 |
url |
http://dx.doi.org/10.1093/rheumatology/keab021 http://hdl.handle.net/11449/229170 |
identifier_str_mv |
Rheumatology (United Kingdom), v. 60, n. 10, p. 4495-4507, 2021. 1462-0332 1462-0324 10.1093/rheumatology/keab021 2-s2.0-85110584854 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Rheumatology (United Kingdom) |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
4495-4507 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1792962416607232000 |