Clinical pharmacology of tocilizumab for the treatment of patients with rheumatoid arthritis

Expert Rev Clin Pharmacol. 2011 Sep;4(5):539-58. doi: 10.1586/ecp.11.33.

Abstract

Tocilizumab is a humanized anti-IL-6 receptor (IL-6R) monoclonal antibody for the treatment of rheumatoid arthritis (RA). A dose of 8 mg/kg produces adequate blockade of IL-6 receptors throughout a dosing interval, as confirmed by sustained high levels of tocilizumab-bound soluble IL6-R complex and normalization of C-reactive protein levels. Studies have confirmed 8 mg/kg every 4 weeks as the optimal dose and 4 mg/kg as the starting dose for the treatment of RA, with favorable efficacy and acceptable safety profiles. After 8 mg/kg, steady-state peak and trough concentrations were 183 ± 86 and 9.7 ± 11 µg/ml, respectively. Tocilizumab serum exposures increased more than proportionally to the dose increase from 2-10 mg/kg. Total clearance is concentration dependent, with non-linear receptor-mediated clearance dominant at low concentrations (<25 µg/ml). Tocilizumab exposures are not affected by common concomitant medications in RA patients, but decreased IL-6 activity resulted in increased CYP3A4 activity and hence decreased exposures of CYP3A4 substrates.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Humans
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Receptors, Interleukin-6 / immunology
  • Receptors, Interleukin-6 / metabolism
  • Treatment Outcome

Substances

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