Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis
Nicolino Ruperto, Hermine I. Brunner, César Pacheco‐Tena, Ingrid Louw, Gabriel Vega‐Cornejo, Alberto Spindler, D. Kingsbury, Heinrike Schmeling, Arturo Borzutzky, Rubén Cuttica, C. Inman, Victor Malievskiy, Christiaan Scott, Vladimir Keltsev, Maria Teresa Terreri, Diego Oscar Viola, Ricardo Machado Xavier, Taciana A Pedrosa Fernandes, María del Rocío Maldonado Velázquez, Michael Henrickson, Michael B. Clark, Karen Bensley, Xiaoming Li, Kim Hung Lo, Jocelyn H. Leu, Chyi‐Hung Hsu, Elizabeth C. Hsia, Zhenhua Xu, Alberto Martini, Daniel J. Lovell, Simone Appenzeller, Sheila Knupp Feitosa de Oliveira, Clóvis A. Silva, Deborah M. Levy, Carmen Navarrete, Yonatan Butbul Aviel, Yosef Uziel, Е.I. Alexeeva, Vladimir Chasnyk, Yury Spivakovsky, Beth S. Gottlieb, Egla Rabinovich, Andrew Zeft, Thomas A. Griffin, Deirdre De Ranieri, Ruy Carrasco
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/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.