Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis. (28th January 2021)

• Record Type: Journal Article
• Authors: Ruperto, Nicolino; Brunner, Hermine I; Ramanan, Athimalaipet V; Horneff, Gerd; Cuttica, Rubén; Henrickson, Michael; Anton, Jordi; Boteanu, Alina Lucica; Penades, Inmaculada Calvo; Minden, Kirsten; Schmeling, Heinrike; Hufnagel, Markus; Weiss, Jennifer E; Pardeo, Manuela; Nanda, Kabita; Roth, Johannes; Rubio-Pérez, Nadina ; Hsu, Joy C; Wimalasundera, Sunethra; Wells, Chris; Bharucha, Kamal ; Douglass, Wendy; Bao, Min; Mallalieu, Navita L; Martini, Alberto; Lovell, Daniel; Benedetti, Fabrizio De
• Is Part Of: Rheumatology. Volume 60:Number 10(2021)
• Page Start: 4568
• Page End: 4580
• Publication Date: 2021-01-28
• Subjects: autoinflammatory conditions -- biologic therapies -- cytokines and inflammatory mediators -- inflammation -- juvenile idiopathic arthritis; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/keab047
• Languages: English
• ISSNs: 1462-0324

Abstract

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 <30 kg, respectively. Primary end points were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with i.v. tocilizumab (i.v.-TCZ) in sJIA and pJIA. 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