Tocilizumab: A Review of its Use in the Management of Rheumatoid Arthritis

Authors: Oldfield, Vicki; Dhillon, Sohita; Plosker, Greg L.

Source: Drugs, Volume 69, Number 5, 26 March 2009 , pp. 609-632(24)

Buy & download fulltext article:

Price: $68.55 plus tax (Refund Policy)

Abstract:

Abstract Tocilizumab (RoActemra® or Actemra®) is a recombinant humanized monoclonal antibody that acts as an interleukin (IL)-6 receptor antagonist. Intravenous tocilizumab 8 mg/kg (and no less than 480 mg), in combination with methotrexate, is approved in the EU for the treatment of moderate to severe active rheumatoid arthritis in adult patients with inadequate response to, or who are intolerant of, prior disease-modifying anti-rheumatic drug (DMARD) or tumour necrosis factor (TNF) antagonist therapy. It may also be administered as monotherapy in patients intolerant of methotrexate or in whom methotrexate therapy is inappropriate. Tocilizumab is also approved in Japan for the treatment of polyarticular-course juvenile idiopathic arthritis, systemic-onset juvenile idiopathic arthritis and Castleman's disease.

Intravenous tocilizumab was effective and generally well tolerated when administered either as monotherapy or in combination with conventional DMARDs in several well designed clinical studies in adult patients with moderate to severe rheumatoid arthritis. Tocilizumab-based therapy was consistently more effective than placebo, methotrexate or other DMARDs in reducing disease activity, and some trials also showed significant benefits with tocilizumab in terms of reducing structural joint damage and improving health-related quality of life (HR-QOL). Notably, tocilizumab-based therapy was effective in patients with long-standing disease in whom anti-TNF therapy had previously failed. More data are required to determine the comparative efficacy and safety of tocilizumab versus other biological agents and to establish their relative cost effectiveness. However, the present data suggest that tocilizumab is an important emerging treatment option in adult patients with moderate to severe rheumatoid arthritis.

Pharmacological Properties Elevated levels of IL-6 in the serum and synovial fluid of rheumatoid arthritis patients contribute to the chronic inflammatory process characterizing this disease and correlate positively with disease activity. Tocilizumab binds selectively and competitively to soluble and membrane-expressed IL-6 receptors, blocking IL-6 signal transduction. In vivo, maximum (>90%) IL-6 receptor saturation was achieved when serum tocilizumab concentrations were >1 μg/mL. In dose-ranging studies, serum levels of inflammatory markers were normalized in rheumatoid arthritis patients who had detectable levels of tocilizumab in the serum. Tocilizumab displays dose-dependent, non-linear pharmacokinetics and has a long elimination half-life, allowing administration every 4 weeks.

Therapeutic Efficacy Several well designed studies in patients with early or long-standing rheumatoid arthritis, including those with treatment-refractory disease, demonstrated the efficacy of intravenous tocilizumab 8 mg/kg every 4 weeks in improving disease activity, structural joint damage and/or HR-QOL.

Monotherapy with tocilizumab 8 mg/kg was noninferior to methotrexate for achievement of a clinical response in patients who had not experienced any prior treatment failures in the AMBITION study; subsequent superiority analyses in the intent-to-treat population demonstrated that significantly more tocilizumab than methotrexate recipients achieved American College of Rheumatology (ACR) clinical responses at week 24. Tocilizumab recipients also demonstrated significant improvements at week 24 in HR-QOL measures.

Among patients with early (mean disease duration <3 years) rheumatoid arthritis whose previous treatment with conventional DMARDs had failed, monotherapy with tocilizumab 8 mg/kg for 1 year was significantly more effective than treatment with DMARDs for achieving an ACR20 response, preventing radiographic disease progression and improving HR-QOL.

Patients with long-standing treatment-refractory disease achieved significantly better clinical responses with tocilizumab 8 mg/kg monotherapy than with placebo or methotrexate. These beneficial effects were maintained for up to 5 years with tocilizumab in a noncomparative extension of a placebo-controlled trial. Five studies of tocilizumab-based combination therapy for up to 52 weeks in patients with long-standing, treatment-refractory disease demonstrated better clinical responses with tocilizumab 8 mg/kg plus methotrexate or other DMARDs than with methotrexate or other DMARDs alone. Improvements in the levels of inflammatory markers were also observed, including serum C-reactive protein levels, which reduced as early as week 2. The mean changes from baseline in HR-QOL outcomes also favoured patients receiving tocilizumab-based combination therapy.

Document Type: Research article

Affiliations: 1: Wolters Kluwer Health ∣ Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health, Philadelphia, Pennsylvania, USA

Publication date: 2009-03-26

Tocilizumab: A Review of its Use in the Management of Rheumatoid Arthritis

Buy & download fulltext article:

Tools

Key

Text size:

Useful pages