Introduction of Tocilizumab

Tocilizumab, also known as atlizumab, is a recombinant humanized, anti-human monoclonal antibody (mAb) of the immunoglobulin G1κ subclass directed against soluble and membrane-bound interleukin-6 (IL-6) receptor (IL-6R) which plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was first approved in 2005 as an orphan drug in Japan for the treatment of Castleman’s disease, a rare lymphoproliferative disease involving expansion of plasma cell numbers. Tocilizumab is now licensed in the EU for use alone or in combination with disease-modifying anti-rheumatic drugs (DMARDs) to treat adult patients with moderate to severely active rheumatoid arthritis (RA), children over 2 y of age with the systemic form of juvenile idiopathic arthritis (sJIA) or children over 2 y of age with the polyarticular form of juvenile idiopathic arthritis (pJIA). It has also been studied as a treatment of other conditions such as Crohn’s disease, systemic lupus erythematosus (SLE), Takayasu arteritis (TA), giant cell arteritis (GCA) polymyalgia rheumatica (PMR) and refractory adult-onset Still disease, but has not yet received licenses in these indications.

Mechanism of Action of Tocilizumab

IL-6 is a multifunctional cytokine that plays an important role in both acute and chronic inflammatory responses. Consequently, the dysregulated or persistent production of IL-6 can lead to the development of inflammatory disorders. Elevated levels of IL-6 in serum, synovial fluid, and various tissues have been correlated with disease activity in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), Castleman’s disease, systemic sclerosis (SSc), giant cell arteritis (GCA), adult-onset Still’s disease (AOSD), familial Mediterranean fever (FMF), Schnitzler’s syndrome, polychondritis, and amyloidosis. Tocilizumab targets the IL-6 receptor subunit alpha (IL-6Rα), and its mechanism of action has been described in detail in previous reviews. Briefly, Tocilizumab targets both membrane-bound and soluble IL-6Rα, which prevents the binding of IL-6 to both the IL-6R and the signal transducer glycoprotein 130 complex and results in turn in inhibition of the downstream classic signaling and trans-signaling cascades involving the Janus-activated kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Through this mechanism, Tocilizumab decreases the circulating levels of neutrophils, neutrophil infiltration into inflamed joints, circulation of myeloid dendritic cells, monocyte levels, serum macrophage migration inhibitory factor levels, and levels of T helper 17 (Th17) cells, while increasing regulatory T cells. Tocilizumab also induces regulatory B-cell expansion, decreases B-cell hyperactivity, and decreases the number of peripheral memory B cells.

Fig.1 Mechanism of action of tocilizumab

What We Provide

For research use only. Not intended for any clinical use.