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).

Antibody therapies for the treatment of COVID-19

“…Azithromycin is a macrolide antibacterial that may prevent bacterial superinfection on COVID-19 patients; macrolides may have immunomodulatory properties in pulmonary inflammatory disorders [23]. Tocilizumab is an interleukin-6 (IL-6) receptor-blocking antibody that inhibits IL-6-mediated signaling for the treatment of inflammatory diseases [24,25]. The rationale for testing the efficacy of tocilizumab against COVID-19 is that IL-6 is a pro-inflammatory cytokine; cytokine release syndrome may be a component of severe disease in COVID-19 patients [26].…”

Cytochrome P450-mediated interactions of monoclonal antibodies and small-molecules drugs

“…Интерлейкин-6. ИЛ-6 -это цитокин, продуцируемый макрофагами и другими типами клеток при воспалении или инфекциях в ответ на различные факторы, такие как ИЛ-1 и ФНОα [26,35]. Влияние этого цитокина на активность ферментов CYP450 установлено в нескольких исследованиях.…”

“…Модуляторы ИЛ-6. Тоцилизумаб -МАТ, которое связывается как с растворимыми, так и с мембранными рецепторами ИЛ-6 [35]. Применяется для лечения ревматоидного артрита и гигантоклеточного артериита.…”

Circulating interleukin‐6 as a biomarker in a randomized controlled trial of modified‐release prednisone vs immediate‐release prednisolone, in newly diagnosed patients with giant cell arteritis

“…Interleukin‐6 (IL‐6) is a pleiotropic cytokine involved in regulation of the immune response, hematopoiesis and inflammation. It is produced by several cell types and binds to the IL‐6 receptor (IL‐6R) and gp130, with homodimerization of these receptor molecules initiating activation of the Janus kinases (JAKs), leading to expression of acute phase response genes . Overproduction of IL‐6 is implicated in the pathogenesis of chronic inflammatory diseases, such as GCA, and elevated serum IL‐6 concentrations correlate well with systemic disease activity compared with other biological markers …”

“…It is produced by several cell types and binds to the IL-6 receptor (IL-6R) and gp130, with homodimerization of these receptor molecules initiating activation of the Janus kinases (JAKs), leading to expression of acute phase response genes. 4,5 Overproduction of IL-6 is implicated in the pathogenesis of chronic inflammatory diseases, such as GCA, and elevated serum IL-6 concentrations correlate well with systemic disease activity compared with other biological markers. [6][7][8][9] Although the efficacy of GCs in control of the disease is well established, they potentially cause serious and chronic adverse reactions, including hypertension, dyslipidemia, diabetes mellitus and osteoporosis; frequency of steroid-induced comorbidities drives the development of GCA treatment protocols requiring reduced GC exposure.…”