Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis.

Autor:	Ruperto N; IRCCS Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, PRINTO, Genoa, Italy., Brunner HI; Cincinnati Children's Hospital Medical Center, Division of Rheumatology, University of Cincinnati, Cincinnati, OH, USA., Pacheco-Tena C; Facultad de Medicina, Universidad Autónoma de Chihuahua, Circuito Universitario Campus II, Chihuahua, México., Louw I; Panorama Medical Centre, Rheumatology Private Practice, Cape Town, South Africa., Vega-Cornejo G; Centro de Reumatología y Autoinmunidad (CREA)/Hospital México Americano, Guadalajara, Jalisco, México., Spindler AJ; Centro Médico Privado de Reumatología, Rheumatology Section, San Miguel de Tucuman, Tucuman, Argentina., Kingsbury DJ; Randall Children's Hospital at Legacy Emanuel, Portland, OR, USA., Schmeling H; Department of Pediatrics, Alberta Children's Hospital, Cumming School of Medicine/University of Calgary, Calgary, Alberta, Canada., Borzutzky A; Department of Pediatric Infectious Diseases and Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile., Cuttica R; Rheumatology Section, Hospital Pedro de Elizalde, Buenos Aires, Argentina., Inman CJ; Pediatric Rheumatology, University of Utah, Salt Lake City, UT, USA., Malievskiy V; Federal State Budget Educational Institution of Higher Education, Bashkir State Medical University of the Ministry of Healthcare of Russian Federation, Ufa, Russian Federation., Scott C; Red Cross War Memorial Children's Hospital and Groote Schuur Hospital, Paediatric Rheumatology, University of Cape Town, Cape Town, South Africa., Keltsev V; Pediatric Department, Clinical Hospital No. 5, Togliatti, Russian Federation., Terreri MT; Escola Paulista de Medicina/Universidade Federal de São Paulo, Pediatrics, São Paulo, Brazil., Viola DO; Instituto CAICI, Rheumatology, Rosario, Argentina., Xavier RM; Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre., Fernandes TAP; Paediatric Department, Hospital das Clinicas-Botucatu Medicine University, UNESP, Botucatu, Brazil., Velázquez MDRM; Hospital Infantil de México Federico Gómez, Medicina Interna y Reumatologia, Mexico City, México., Henrickson M; Cincinnati Children's Hospital Medical Center, Cincinnati, OH., Clark MB; Janssen Research & Development, LLC, Spring House, PA., Bensley KA; Janssen Research & Development, LLC, Spring House, PA., Li X; Janssen Research & Development, LLC, Spring House, PA., Lo KH; Janssen Research & Development, LLC, Spring House, PA., Leu JH; Janssen Research & Development, LLC, Spring House, PA., Hsu CH; Janssen Research & Development, LLC, Raritan, NJ, USA., Hsia EC; Janssen Research & Development, LLC, Spring House, PA., Xu Z; Janssen Research & Development, LLC, Spring House, PA., Martini A; Università degli Studi di Genova, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Genova, Italy., Lovell DJ; Cincinnati Children's Hospital Medical Center, Division of Rheumatology, University of Cincinnati, Cincinnati, OH, USA.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2021 Oct 02; Vol. 60 (10), pp. 4495-4507.
DOI:	10.1093/rheumatology/keab021
Abstrakt:	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. (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
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