Long-term efficacy and safety of subcutaneous tocilizumab in clinical trials of polyarticular or systemic juvenile idiopathic arthritis
Hermine I. Brunner, Nicolino Ruperto, Athimalaipet V Ramanan, Gerd Horneff, Kirsten Minden, Inmaculada Calvo Penadés, Е.I. Alexeeva, Gavin Cleary, Sara Stern, Isabelle Koné‐Paut, María del Rocío Maldonado Velázquez, C. Egla Rabinovich, Agustín Remesal, Clóvis A. Silva, И. П. Никишина, Mauro Zucchetto, Laura Brockwell, Oliver Gordon, Sandra Nagel, Fabrizio De Benedetti, for the PRINTO and PRCSG Investigators, Rubén Cuttica, Maria Elena Rama, Jonathan Akikusa, Jeffrey Chaitow, Cláudio Arnaldo Len, Clóvis A. Silva, Heinrike Schmeling, Rayfel Schneider, Isabelle Koné‐Paut, Markus Hufnagel, Kirsten Minden, Gerd Horneff, Fabrizio De Benedetti, María del Rocío Maldonado Velázquez, Nadina Rubio, Е.I. Alexeeva, Agustín Remesal, Alina Boteanu, Rosa Bou, Inmaculada Calvo Penades, Athimalaipet V Ramanan, Gavin Cleary, Hermine I. Brunner, Ginger Janow, Jennifer E. Weiss, Daniel J. Lovell, Alan Martin, Kabita Nanda, Linda Wagner‐Weiner, Sara Stern, Andrew Zeft, Jason Dare
Abstract
OBJECTIVE: To investigate the safety and efficacy of subcutaneous tocilizumab (SC-TCZ) treatment in a long-term extension (LTE) of clinical trials in polyarticular or systemic juvenile idiopathic arthritis (pJIA or sJIA). METHODS: Patients with pJIA or sJIA from two open-label, 52-week phase 1b core trials of SC-TCZ who had adequate response per investigator assessment entered the LTE and continued SC-TCZ treatment according to body weight-based dosing regimens until commercial availability or up to 5 years. Pharmacokinetics, pharmacodynamics, and efficacy were assessed for up to 3 years, and safety for up to 5 years in the LTE. RESULTS: Forty-four patients with pJIA and 38 patients with sJIA entered the LTE. Tocilizumab trough concentrations were maintained within the range expected to provide clinical benefit (mean values: pJIA, ∼10 μg/ml; sJIA, ∼75 μg/ml over 3 years). Pharmacodynamic parameters (interleukin-6, soluble interleukin-6 receptor, erythrocyte sedimentation rate, C-reactive protein) were maintained throughout the LTE at levels achieved in the core trials. Inactive disease per American College of Rheumatology provisional criteria was reported for 90% (17/19) and 53% (8/15) of patients with pJIA and 91% (10/11) and 92% (12/13) of patients with sJIA in the <30 and ≥30 kg body weight groups, respectively. Serious adverse events in the LTE were reported in six patients with pJIA (13.6%; five serious infections) and five patients with sJIA (13.2%; one serious infection). CONCLUSION: Patients with pJIA or sJIA experienced long-term disease control with SC-TCZ treatment. Long-term safety was consistent with the known tocilizumab safety profile. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, NCT02165345.