Beneficial Effect of Corticosteroids in Preventing Mortality in Patients Receiving Tocilizumab to Treat Severe COVID-19 Illness

Abstract

Introduction: On the basis of the preliminary report from the RECOVERY trial, the use of dexamethasone or alternative corticosteroids (CS) is currently recommended in severe COVID-19 patients requiring supplemental oxygen. However, last updated recommendations have not taken a position either for or against the use of other immunomodulators such as tocilizumab (TCZ), with or without CS, since results are still limited. Methods: From March 17 to April 7, 2020, a real-world observational retrospective analysis was conducted at our 750-bed university hospital to study the characteristics and risk factors for mortality in patients with severe COVID-19 treated with TCZ, with or without CS, in addition to standard of care (SOC). Data were obtained from routine clinical practice, stored in electronic medical records. The main outcome was all-cause in-hospital mortality. Results: A total of 1,092 COVID-19 patients were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186, 155 (83.3 %) patients were receiving non-invasive ventilation when TCZ, with or without CS was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (SD 4.3) and 4.3 days (SD 3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR=1.09, p<0.001), chronic heart failure (HR=4.4, p=0.003), and chronic liver disease (HR=4.69, p=0.004). The use of CS, in combination with TCZ, was the main protective factor against mortality (HR=0.26, p<0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. Conclusions: In severe COVID-19 patients receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in combined therapy with TCZ, was the main protective factor against in-hospital mortality.

Divergent impacts of tocilizumab and colchicine in COVID‐19‐associated coagulopathy: the role of alpha‐defensins

“…However, in line with the data of others, 7,10 we observed that IL-6 levels measured 24 h after an initial IV dose of TCZ increased significantly compared with pretreatment levels (Fig 1A ), presumably as a consequence of inhibiting uptake of the cytokine by its receptors. The increase in IL-6 was accompanied by an increase in D-dimers (Fig 1B ) and, in line with our previous data, 18 by an increase in plasma a-Def (Fig 1C).…”

“…However, clinical trials with TCZ have not provided the expected benefits. 4,5 Indeed, an increase in D-dimers, a marker of fibrin turnover, has been recorded unexpectedly in TCZ-treated patients in some trials, [6][7][8][9][10] together with a trend to a higher death rate secondary to thromboembolism in one study. 11 Although it has been suggested that the protective effect reported of TCZ in some studies might be corticosteroiddependent, 12 other studies showed an increase in D-dimers in patients treated with TCZ whether or not corticosteroids were co-administered.…”

“…11 Although it has been suggested that the protective effect reported of TCZ in some studies might be corticosteroiddependent, 12 other studies showed an increase in D-dimers in patients treated with TCZ whether or not corticosteroids were co-administered. 10 The beneficial effect of colchicine, another anti-inflammatory medication used to treat patients with COVID-19 has also been inconsistent, [13][14][15][16] but in contrast to TCZ, treatment reduced D-dimer levels. 14,17 We sought to understand how two anti-inflammatory agents, TCZ and colchicine, differ in their effects on D-dimer levels with the hope that these results might be used to improve efficacy in patients with COVID-19, rheumatoid arthritis and other inflammatory conditions.…”

“…Although it has been suggested that the protective effect reported of TCZ in some studies might be corticosteroid‐dependent, 12 other studies showed an increase in D‐dimers in patients treated with TCZ whether or not corticosteroids were co‐administered 10 . The beneficial effect of colchicine, another anti‐inflammatory medication used to treat patients with COVID‐19 has also been inconsistent, 13–16 but in contrast to TCZ, treatment reduced D‐dimer levels 14,17 …”

Corticosteroids for Patients With Coronavirus Disease 2019 (COVID-19) With Different Disease Severity: A Meta-Analysis of Randomized Clinical Trials

“…Excluding 1,157 nonpertinent titles or abstracts, the authors retrieved (in complete form) and assessed 11 studies according to the selection criteria (Fig 1). Six studies were further excluded because of the prespecified exclusion criteria: five because they were not randomized, [18][19][20][21][22] and one because it did not report outcomes of randomized patients. 23 The five RCTs finally included in the meta-analysis involved 7,692 patients (2,835 received corticosteroids and 4,837 received standard treatment 8,10-13 ; Table 1).…”