Objectives: To determine subcutaneous-tocilizumab (SC-TCZ) dosing regimens for systemic juvenile idiopathic arthritis (sJIA) and polyarticular JIA (pJIA).
Methods: In two 52-week phase 1 b trials, SC-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 endpoints were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with intravenous-tocilizumab (IV-TCZ) in sJIA and pJIA.
Results: Study participants were 51 sJIA patients and 52 pJIA patients aged 1-17 years who received SC-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with IV-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 Disease Activity Score-71 were comparable between SC-TCZ and IV-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of IV-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 related to TCZ.
Conclusion: SC-TCZ provides exposure and risk/benefit profiles similar to those of IV-TCZ. Subcutaneous administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use.
Keywords: Autoinflammatory conditions; Biological therapies; Cytokines and inflammatory mediators; Inflammation; Juvenile Idiopathic Arthritis.
© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.