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/11449/218692 |
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 >= 2months received 80 mg/m(2) 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 (AUC(ss)) 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 AUC(ss) were 0.40 mu g/ml and 399 mu g. day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUC(ss) were consistent across age categories and comparable to i.v. golimumab dosed 2mg/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. |
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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 >= 2months received 80 mg/m(2) 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 (AUC(ss)) 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 AUC(ss) were 0.40 mu g/ml and 399 mu g. day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUC(ss) were consistent across age categories and comparable to i.v. golimumab dosed 2mg/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.Janssen Research & Development, LLCIRCCS Ist Giannina Gaslini Clin Pediat & Reumatol, PRINTO, Genoa, ItalyUniv Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH USAUniv Autonoma Chihuahua, Fac Med, Circuito Univ Campus 2, Chihuahua, MexicoPanorama Med Ctr, Cape Town, South AfricaHosp Mexico Americano, Ctr Reumatol & Autoinmunidad CREA, Guadalajara, Jalisco, MexicoCtr Med Privado Reumatol, Rheumatol Sect, San Miguel De Tucuman, Tucuman, ArgentinaRandall Childrens Hosp Legacy Emanuel, Portland, OR USAUniv Calgary, Alberta Childrens Hosp, Cumming Sch Med, Dept Pediat, Calgary, AB, CanadaPontificia Univ Catolica Chile, Sch Med, Dept Pediat Infect Dis & Immunol, Santiago, ChileHosp Pedro de Elizalde, Rheumatol Sect, Buenos Aires, DF, ArgentinaUniv Utah, Pediat Rheumatol, Salt Lake City, UT USABashkir State Med Univ Minist Healthcare Russian, Fed State Budget Educ Inst Higher Educ, Ufa, RussiaUniv Cape Town, Red Cross War Mem Childrens Hosp, Cape Town, South AfricaUniv Cape Town, Groote Schuur Hosp, Paediat Rheumatol, Cape Town, South AfricaClin Hosp 5, Pediat Dept, Tolyatti, RussiaUniv Fed Sao Paulo, Escola Paulista Med, Pediat, Sao Paulo, BrazilInst CAICI, Rheumatol, Rosario, ArgentinaUniv Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Porto Alegre, RS, BrazilUNESP, Hosp Clin Botucatu Med Univ, Paediat Dept, Botucatu, SP, BrazilHosp Infantil Mexico Dr Federico Gomez, Med Interna & Reumatol, Mexico City, DF, MexicoCincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USAJanssen Res & Dev LLC, Spring House, PA USAJanssen Res & Dev LLC, Raritan, NJ USAUniv Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, Genoa, ItalyUNESP, Hosp Clin Botucatu Med Univ, Paediat Dept, Botucatu, SP, BrazilOxford Univ PressIRCCS Ist Giannina Gaslini Clin Pediat & ReumatolUniv CincinnatiUniv Autonoma ChihuahuaPanorama Med CtrHosp Mexico AmericanoCtr Med Privado ReumatolRandall Childrens Hosp Legacy EmanuelUniv CalgaryPontificia Univ Catolica ChileHosp Pedro de ElizaldeUniv UtahBashkir State Med Univ Minist Healthcare RussianUniv Cape TownClin Hosp 5Universidade Federal de São Paulo (UNIFESP)Inst CAICIUniv Fed Rio Grande do SulUniversidade Estadual Paulista (UNESP)Hosp Infantil Mexico Dr Federico GomezCincinnati Childrens Hosp Med CtrJanssen Res & Dev LLCUniv GenoaRuperto, NicolinoBrunner, HerminePacheco-Tena, CesarLouw, IngridVega-Cornejo, GabrielSpindler, Alberto J.Kingsbury, Daniel J.Schmeling, HeinrikeBorzutzky, ArturoCuttica, RubenInman, C. J.Malievskiy, VictorScott, ChristiaanKeltsev, VladimirTerreri, Maria TeresaViola, Diego OscarXavier, Ricardo M.Fernandes, Taciana A. Pedrosa [UNESP]Maldonado Velazquez, Maria del RocioHenrickson, MichaelClark, Michael B.Bensley, Karen A.Li, XiaomingLo, Kim HungLeu, Jocelyn H.Hsu, Chyi-HungHsia, Elizabeth C.Xu, ZhenhuaMartini, AlbertoLovell, Daniel J.Pediat Rheumatology CollaborativePaediat Rheumatology Int Trials Or2022-04-28T17:22:32Z2022-04-28T17:22:32Z2021-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article4495-4507http://dx.doi.org/10.1093/rheumatology/keab021Rheumatology. Oxford: Oxford Univ Press, v. 60, n. 10, p. 4495-4507, 2021.1462-0324http://hdl.handle.net/11449/21869210.1093/rheumatology/keab021WOS:000709572600017Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengRheumatologyinfo:eu-repo/semantics/openAccess2024-09-03T13:47:03Zoai:repositorio.unesp.br:11449/218692Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T13:47:03Repositório 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 Pacheco-Tena, Cesar Louw, Ingrid Vega-Cornejo, Gabriel Spindler, Alberto J. Kingsbury, Daniel J. Schmeling, Heinrike Borzutzky, Arturo Cuttica, Ruben Inman, C. J. Malievskiy, Victor Scott, Christiaan Keltsev, Vladimir Terreri, Maria Teresa Viola, Diego Oscar Xavier, Ricardo M. Fernandes, Taciana A. Pedrosa [UNESP] Maldonado Velazquez, Maria del Rocio 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. Pediat Rheumatology Collaborative Paediat Rheumatology Int Trials Or |
author_role |
author |
author2 |
Brunner, Hermine Pacheco-Tena, Cesar Louw, Ingrid Vega-Cornejo, Gabriel Spindler, Alberto J. Kingsbury, Daniel J. Schmeling, Heinrike Borzutzky, Arturo Cuttica, Ruben Inman, C. J. Malievskiy, Victor Scott, Christiaan Keltsev, Vladimir Terreri, Maria Teresa Viola, Diego Oscar Xavier, Ricardo M. Fernandes, Taciana A. Pedrosa [UNESP] Maldonado Velazquez, Maria del Rocio 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. Pediat Rheumatology Collaborative Paediat Rheumatology Int Trials Or |
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 |
dc.contributor.none.fl_str_mv |
IRCCS Ist Giannina Gaslini Clin Pediat & Reumatol Univ Cincinnati Univ Autonoma Chihuahua Panorama Med Ctr Hosp Mexico Americano Ctr Med Privado Reumatol Randall Childrens Hosp Legacy Emanuel Univ Calgary Pontificia Univ Catolica Chile Hosp Pedro de Elizalde Univ Utah Bashkir State Med Univ Minist Healthcare Russian Univ Cape Town Clin Hosp 5 Universidade Federal de São Paulo (UNIFESP) Inst CAICI Univ Fed Rio Grande do Sul Universidade Estadual Paulista (UNESP) Hosp Infantil Mexico Dr Federico Gomez Cincinnati Childrens Hosp Med Ctr Janssen Res & Dev LLC Univ Genoa |
dc.contributor.author.fl_str_mv |
Ruperto, Nicolino Brunner, Hermine Pacheco-Tena, Cesar Louw, Ingrid Vega-Cornejo, Gabriel Spindler, Alberto J. Kingsbury, Daniel J. Schmeling, Heinrike Borzutzky, Arturo Cuttica, Ruben Inman, C. J. Malievskiy, Victor Scott, Christiaan Keltsev, Vladimir Terreri, Maria Teresa Viola, Diego Oscar Xavier, Ricardo M. Fernandes, Taciana A. Pedrosa [UNESP] Maldonado Velazquez, Maria del Rocio 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. Pediat Rheumatology Collaborative Paediat Rheumatology Int Trials Or |
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 >= 2months received 80 mg/m(2) 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 (AUC(ss)) 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 AUC(ss) were 0.40 mu g/ml and 399 mu g. day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUC(ss) were consistent across age categories and comparable to i.v. golimumab dosed 2mg/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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-10-01 2022-04-28T17:22:32Z 2022-04-28T17:22:32Z |
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. Oxford: Oxford Univ Press, v. 60, n. 10, p. 4495-4507, 2021. 1462-0324 http://hdl.handle.net/11449/218692 10.1093/rheumatology/keab021 WOS:000709572600017 |
url |
http://dx.doi.org/10.1093/rheumatology/keab021 http://hdl.handle.net/11449/218692 |
identifier_str_mv |
Rheumatology. Oxford: Oxford Univ Press, v. 60, n. 10, p. 4495-4507, 2021. 1462-0324 10.1093/rheumatology/keab021 WOS:000709572600017 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Rheumatology |
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.publisher.none.fl_str_mv |
Oxford Univ Press |
publisher.none.fl_str_mv |
Oxford Univ Press |
dc.source.none.fl_str_mv |
Web of Science 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 |
repositoriounesp@unesp.br |
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1810021417592291328 |