Clinical pharmacology of tocilizumab for the treatment of patients with rheumatoid arthritis. Issue 5 (September 2011)

• Record Type: Journal Article
• Authors: Zhang, Xiaoping; Peck, Richard
• Is Part Of: Expert review of clinical pharmacology. Volume 4:Issue 5(2011)
• Page Start: 539
• Page End: 558
• Publication Date: 2011-09
• Subjects: Actemra® -- clinical pharmacology -- C-reactive protein -- exposure–response relationship -- interleukin-6 receptor -- interleukin-6 -- pharmacokinetics -- rheumatoid arthritis -- tocilizumab; Clinical pharmacology -- Periodicals; 615.105
• DOI: 10.1586/ecp.11.33
• Languages: English
• ISSNs: 1751-2433

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.