Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis. (26th January 2021)

• Record Type: Journal Article
• Authors: 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; 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
• Is Part Of: Rheumatology. Volume 60:Number 10(2021)
• Page Start: 4495
• Page End: 4507
• Publication Date: 2021-01-26
• Subjects: golimumab -- intravenous -- juvenile idiopathic arthritis -- pharmacokinetics -- tumour necrosis factor alpha; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/keab021
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: 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/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 (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