1. Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis
- Author
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Jordi Anton, Navita L. Mallalieu, Heinrike Schmeling, Gerd Horneff, Fabrizio De Benedetti, Inmaculada Calvo Penades, Alina Boteanu, Kabita Nanda, Daniel J. Lovell, Min Bao, Kamal N. Bharucha, Nicolino Ruperto, Michael Henrickson, Sunethra Wimalasundera, Johannes Roth, Manuela Pardeo, Jennifer E. Weiss, Athimalaipet V Ramanan, Nadina Rubio-Pérez, Wendy Douglass, Alberto Martini, Chris Wells, Joy C. Hsu, Hermine I. Brunner, Kirsten Minden, Markus Hufnagel, and Ruben Cuttica
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Adolescent ,Injections, Subcutaneous ,Arthritis ,Antibodies, Monoclonal, Humanized ,Drug Administration Schedule ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tocilizumab ,Rheumatology ,Pharmacokinetics ,autoinflammatory conditions ,Internal medicine ,biologic therapies ,Injection site ,medicine ,Juvenile ,Humans ,Pharmacology (medical) ,Dosing ,Child ,AcademicSubjects/MED00360 ,030203 arthritis & rheumatology ,Dose-Response Relationship, Drug ,business.industry ,Infant ,Clinical Science ,medicine.disease ,Interim analysis ,Arthritis, Juvenile ,030104 developmental biology ,Treatment Outcome ,chemistry ,inflammation ,Pharmacodynamics ,Antirheumatic Agents ,Child, Preschool ,juvenile idiopathic arthritis ,Female ,cytokines and inflammatory mediators ,business - Abstract
Objectives To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA). Methods In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or Results Study participants were 51 sJIA patients and 52 pJIA patients aged 1–17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ. Conclusion s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904292 and NCT01904279
- Published
- 2021