Author(s):
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
Date: 2022
Persistent ID: http://hdl.handle.net/11449/229170
Origin: Oasisbr
Subject(s): Golimumab; Intravenous; Juvenile idiopathic arthritis; Pharmacokinetics; Tumour necrosis factor alpha
Description
Made available in DSpace on 2022-04-29T08:30:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01
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
IRCCS Istituto Giannina Gaslini Clinica Pediatrica e Reumatologia PRINTO
Cincinnati Children's Hospital Medical Center Division of Rheumatology University of Cincinnati
Facultad de Medicina Universidad Autónoma de Chihuahua Circuito Universitario Campus II
Panorama Medical Centre Rheumatology Private Practice
Centro de Reumatología y Autoinmunidad (CREA) Hospital México Americano, Jalisco
Centro Médico Privado de Reumatología Rheumatology Section, San Miguel de Tucuman
Randall Children's Hospital at Legacy Emanuel
Department of Pediatrics Alberta Children's Hospital Cumming School of Medicine University of Calgary
Department of Pediatric Infectious Diseases and Immunology School of Medicine Pontificia Universidad Católica de Chile
Rheumatology Section Hospital Pedro de Elizalde
Pediatric Rheumatology University of Utah
Federal State Budget Educational Institution of Higher Education Bashkir State Medical University Ministry of Healthcare of Russian Federation
Red Cross War Memorial Children's Hospital Groote Schuur Hospital University of Cape Town
Pediatric Department Clinical Hospital No. 5
Escola Paulista de Medicina Universidade Federal de São Paulo
Instituto CAICI
Hospital de Clínicas de Porto Alegre Universidade Federal Do Rio Grande Do sul
Paediatric Department Hospital das Clinicas-Botucatu Medicine University UNESP
Hospital Infantil de México Federico Gómez Medicina Interna y Reumatologia
Cincinnati Children's Hospital Medical Center
Janssen Research and Development LLC
Università Degli Studi di Genova Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili
Paediatric Department Hospital das Clinicas-Botucatu Medicine University UNESP
