Aug 8, 2020
Reviewed by Razan El Ramahi, M.B.B.S.
Due to the proinflammatory state observed in patients with COVID-19, it has been hypothesized that immunomodulators will help by inhibiting cytokines and quelling “the storm.” Since patients infected with SARS-CoV-2 have elevated interleukin-6 (IL-6) levels, anti-IL-6 agents were among the first to be explored for this purpose and several studies followed thereafter.
In a study published in The Lancet Rheumatology, authors from three hospitals in Italy retrospectively observed the effects of tocilizumab on a composite outcome of invasive mechanical ventilation (IMV) or death in patients with severe COVID-19 pneumonia. All patients received standard of care (SOC) treatment which included supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin. Over 2 months, 544 patients were included. A subset of 179 subjects had received tocilizumab in addition to SOC (88 received intravenous and 91 received subcutaneous formulations). Fifty-three patients in the tocilizumab group received glucocorticoids. Initiation of IMV was comparable between patients who received SOC alone versus tocilizumab and SOC (16% vs 18% respectively, P =0.41). Death occurred more frequently in the SOC group compared to the tocilizumab and SOC group (20% versus 7%, P = 0.0007). After adjusting for confounding factors, tocilizumab showed significant reduction in the risk for the composite outcome of IMV or death (adjusted hazard ratio 0.61, 95% confidence interval 0.42-0.92; P = 0.020). There was no significant difference between intravenous and subcutaneous tocilizumab.
This retrospective analysis showed that addition of tocilizumab to SOC in the treatment of severe COVID-19 pneumonia may reduce the risk of IMV or death but another significant finding was the increase in new infections diagnosed in patients who received tocilizumab (13%) compared to 4% in the SOC only group. The risk reduction was more significant in patients with worse oxygenation at baseline suggesting that tocilizumab best helps patients at increased risk of IMV or death. Before widespread use of anti-IL-6 agents, we need randomized trials that will examine optimal dose and timing of administration, define subpopulations that will benefit the most, and guide monitoring for short- and long-term adverse events.