Tocilizumab (Actemra)

Abstract

Tocilizumab (TCZ), is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody which has a main use in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA). This article provides an overview of TCZ including looking into the past at the discovery of interleukin-6 (IL-6) as a pro-inflammatory cytokine. It also looks at how tocilizumab was developed, manufactured and tested to ensure both safety and efficacy in a human population. The article then explores the advantages and disadvantages of using TCZ when compared to other biologics approved in RA, sJIA and pJIA and finally looks ahead to the future and the emerging role of IL-6 and its blockade by TCZ as a treatment for giant cell arteritis (GCA), polymyalgia rheumatica (PMR) and large vessel vasculitis (LVV).

Keywords: giant cell arteritis; interleukin-6; monoclonal antibody; rheumatoid arthritis; tocilizumab; vasculitis.

Figure 1.

Overview of the process required to produce a biologic medicinal product. The production process is broken down into 2 main parts. The upstream processes are responsible for genetic manipulation of a host cell and the subsequent large scale production of the drug substance. The downstream processes are responsible for the purification of the drug substance and its formulation into a drug product.

Figure 2.

The development and isolation of tocilizumab producing seed cells. This figure adapted from the production section of the IV tocilizumab EPAR, details the insertion of the gene coding for tocilizumab production into a host CHO cell and the subsequent processes to isolate and culture the tocilizumab producing CHO cell into a viable master and working cell bank.