1. Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis
- Author
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Ruperto, Nicolino, Brunner, Hermine, I, Ramanan, Athimalaipet, V, Horneff, Gerd, Cuttica, Ruben, Henrickson, Michael, Anton, Jordi, Lucica Boteanu, Alina, Calvo Penades, Inmaculada, Minden, Kirsten, Schmeling, Heinrike, Hufnagel, Markus, Weiss, Jennifer E., Pardeo, Manuela, Nanda, Kabita, Roth, Johannes, Rubio-Perez, Nadina, Hsu, Joy C., Wimalasundera, Sunethra, Wells, Chris, Bharucha, Kamal, Douglass, Wendy, Bao, Min, Mallalieu, Navita L., Martini, Alberto, Lovell, Daniel, De Benedetti, Fabrizio, Ruperto, Nicolino, Brunner, Hermine, I, Ramanan, Athimalaipet, V, Horneff, Gerd, Cuttica, Ruben, Henrickson, Michael, Anton, Jordi, Lucica Boteanu, Alina, Calvo Penades, Inmaculada, Minden, Kirsten, Schmeling, Heinrike, Hufnagel, Markus, Weiss, Jennifer E., Pardeo, Manuela, Nanda, Kabita, Roth, Johannes, Rubio-Perez, Nadina, Hsu, Joy C., Wimalasundera, Sunethra, Wells, Chris, Bharucha, Kamal, Douglass, Wendy, Bao, Min, Mallalieu, Navita L., Martini, Alberto, Lovell, Daniel, and De Benedetti, Fabrizio
- 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 (C-trough) >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.
- Published
- 2021