What is Tocilizumab?
Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor, initially indicated only for use in patients with moderate and severe rheumatoid arthritis, but has now been FDA approved for other conditions including cytokine release syndrome, a notable side effect of CAR-T cell therapy.
Cytokine storm in Covid-19 ?
- The specific details on the pathogenesis of SARS-CoV-2 remain unknown. However, there is evidence that pathogenic T helper cells may activate inflammatory CD14+ CD16+ monocytes, who are in turn responsible for the high expression of IL-6 that potentiates the inflammatory response in the pulmonary circulation.
- Patients with severe Covid-19 typically have elevated IL-6, G-CSF and other pro-inflammatory cytokines, with high CRP, LDH with lymphocytopenia, lower NK cells in peripheral blood, and a predominant monocytic infiltration in the lungs. This inflammatory cascade ultimately leads to hypoxemic respiratory failure, multiorgan dysfunction and death.
Tocilizumab for Covid-19 ?
- By blocking IL-6 receptor signaling, tocilizumab has shown to robustly inhibit NF-kB activation and the Janus kinase signaling pathway with an upregulation of P-glycoprotein expression in pulmonary tissue that collectively have a protective effect against sepsis-induced ALI in rat models.
- In twenty one patients diagnosed with severe Covid-19 (with elevated CRP and IL-6) in China, tocilizumab in addition to routine therapy was used. A single dose of 400mg IV of tocilizumab was administered in 18 of 21 patients. The clinical response was robust with a significant decrease in O2 supplementation, fewer lung opacities on CT and improved lymphocyte count in most patients, with 19 of 21 patients discharged ~13.5 days after treatment onset, and the remaining 2 recovering well.
- Tocilizumab was also successfully used in several patients diagnosed with Covid-19 who have underlying malignancies, including one patient with multiple myeloma and another with metastatic clear cell renal cell carcinoma.
Despite preliminary evidence suggesting the potential benefit of tocilizumab in severe Covid-19, its routine use in these patients cannot be recommended until more evidence becomes available.
- Xu X, Han M, Li T et coll. Effective Treatment of severe COVID-19 patients with tocilizumab. chinaXiv:202003.00026v1
- A multicenter, randomized controlled trial for the efficacy and safety of tocilizumab in the treatment of new coronavirus pneumonia (COVID-19). http://www.chictr.org.cn/showprojen.aspx
- Ibrahim, Y.F., Moussa, R.A., Bayoumi, A.M.A. et al. Tocilizumab attenuates acute lung and kidney injuries and improves survival in a rat model of sepsis via down-regulation of NF-κB/JNK: a possible role of P-glycoprotein. Inflammopharmacol 28, 215–230 (2020). https://doi.org/10.1007/s10787-019-00628-y
- INESSS COVID-19 et Tocilizumab. https://www.inesss.qc.ca/covid-19/traitements-specifiques-a-la-covid-19/tocilizumab-actemra.html