Tocilizumab: An lnterleukin-6 Receptor Inhibitor for the Treatment of Rheumatoid Arthritis

Abstract

Objective: To review the pharmacology, pharmacokinetics, clinical trial data, and safety profile of tocilizumab, a new biologic agent targeting the lnterleukin-6 cytokine receptor. Data Sources: A systematic search of MEDLINE (1998–June 2008) and International Pharmaceutical Abstracts (1970–June 2008) was performed to identify published clinical trials and review articles. Key search terms were tocilizumab, MRA, interleukin-6/receptors, interleukln-6/immunology, and rheumatoid arthritis. The search was limited to studies in humans that were published in the English language. References from articles located during this search were evaluated for other relevant citations. Abstracts from national and international rheumatology meetings (American College of Rheumatology and European League Against Rheumatism) and from unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov ) were also reviewed. Study Selection and Data Extraction: All available human studies describing the pharmacology, pharmacokinetics, efficacy, safety, and adverse effects of tocilizumab were included. Data Synthesis: At doses greater than 4 mg/kg, tocilizumab use has resulted In significant improvement in clinical outcomes, including the American College of Rheumatology parameters indicating a patient's level of improvements and disease remission. Improvements were noted when tocilizumab was used as monotherapy or in combination with methotrexate or other disease-modifying antirheumatic drugs. The most effective dose of tocilizumab appears to be 8 mg/kg, which has shown significant improvements in radiographic measures of joint damage. The most common adverse effects have included abnormal results of liver function tests, hyperlipidemia, neutropenia, infections, nasopharyngitis, gastrointestinal complaints, musculoskeletal disorders, headache, rash, and pruritus. Conclusions: Tocilizumab represents a promising new treatment for rheumatoid arthritis. Additional research is warranted to confirm its radiographic benefits, clarify its safely profile, and identify its place in rheumatoid arthritis treatment relative to current biologic agents.