Tocilizumab in the Treatment of Adult Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is the most prevalent immune-mediated chronic rheumatic disease and is associated with joint destruction and disability. Therapeutic strategies, including biological disease-modifying antirheumatic drugs (bDMARDs) have improved the prognosis and quality of life of RA patients. Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6 receptor licensed in 2009 that has demonstrated clinical efficacy in various adult RA populations. RA management guidelines and recommendations consider TCZ as one of the bDMARDS indicated after methotrexate or other conventional synthetic DMARDs and/or TNF inhibitors failure in adult RA. Of particular interest is the demonstration of its effectiveness in monotherapy in comparison with other bDMARDs. Recent observational studies have shown good results for the safety profile of TCZ with no new alert signals.

Exposure‐response modeling of tocilizumab in rheumatoid arthritis using continuous composite measures and their individual components

“…Tocilizumab is a humanized IgG1 monoclonal antibody that competitively inhibits interleukin 6 (IL‐6) by binding to both its soluble and membrane‐bound receptors, thus blocking the transduction signal triggered by the IL‐6/IL‐6 receptor complex . It is approved for the treatment of adult rheumatoid arthritis (RA) patients who have failed to respond to conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) and/or tumour necrosis factor antagonists .…”

Dendritic cells in COVID-19 immunopathogenesis: insights for a possible role in determining disease outcome

“…This strategy may also be effective at reducing COVID-19 mortality in older patients since IL-6 is the most prominent cytokine of the senescence-associated secretory phenotype (SASP) [12,158]. Following this reasoning, another alternative drug for the control of cytokine release syndrome associated to COVID-19 is the humanized monoclonal antibody tocilizumab, which it targets IL-6 receptor [159]. In fact, there are several U. S. Food and Drug Administration (FDA)-approved clinical trials that are ongoing or recruiting patients to assess whether tocilizumab is therapeutic for COVID-19 patients [160][161][162][163][164].…”

The Imperfect Cytokine Storm

“…Immunomodulatory biologics such as tocilizumab are reserved for severe COVID-19 defined by the presence of both worsening respiratory failure and cytokine storm as evidenced by increasing inflammatory markers. Still, caution is warranted as major adverse effects of tocilizumab include infection, infusion reactions, dyslipidemia, neutropenia, and potential malignancy [6]. Patients on LVAD support are particularly vulnerable to infectious complications due to the inherent presence of hardware and driveline exposure as well as the fact that prolonged support has been associated with immune dysregulation [5].…”