Long-term efficacy and safety of subcutaneous tocilizumab in clinical trials of polyarticular or systemic juvenile idiopathic arthritis

Rheumatology (Oxford). 2024 Sep 1;63(9):2535-2546. doi: 10.1093/rheumatology/keae180.

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.

Keywords: autoinflammatory conditions; biologic therapies; clinical trial; interleukin-6; juvenile idiopathic arthritis; long-term extension; paediatric/juvenile rheumatology; pharmacology; pharmacovigilance; tocilizumab.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / pharmacokinetics
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antirheumatic Agents* / administration & dosage
  • Antirheumatic Agents* / adverse effects
  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Juvenile* / drug therapy
  • C-Reactive Protein / metabolism
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Injections, Subcutaneous
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / blood
  • Male
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Treatment Outcome

Substances

  • tocilizumab
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • C-Reactive Protein
  • Receptors, Interleukin-6
  • Interleukin-6

Associated data

  • ClinicalTrials.gov/NCT02165345

Grants and funding