Tocilizumab in patients with severe COVID-19: a retrospective cohort study

Abstract

Background No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment.Methods This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score. FindingsOf 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0•41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p<0•0001) patients treated with tocilizumab (six [7%] treated intravenously and seven [8%] treated subcutaneously). After adjustment for sex, age, recruiting centre, duration of symptoms, and SOFA score, tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0•61, 95% CI 0•40-0•92; p=0•020). 24 (13%) of 179 patients treated with tocilizumab were diagnosed with new infections, versus 14 (4%) of 365 patients treated with standard of care alone (p<0•0001).Interpretation Treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia.

Effects of Tocilizumab in COVID-19 patients: a cohort study

“…Campochiaro et al found no signi cant difference in 28-day mortality (15% vs. 22%, p = 0.15) whereas Somers et al identi ed a 45% reduction in the risk of death (aHR 0.55, 95% CI 0.33-0.90) in mechanically ventilated patients [14,25]. Guaraldi et al also found tocilizumab to be associated with a reduced risk of all-cause mortality after adjusting for age, sex, recruiting center, duration of symptoms, and SOFA score (aHR 0.38, 95% CI 0.17-0.83) [15]. Overall, these ndings suggest a possile mortality bene t with tocilizumab, however it is important to recognize that many patients also received steroids, which has been independently associated with improved survival [27].…”

“…[8]. Limited observational studies have demonstrated tocilizumab to be associated with improvements in in ammatory markers, clinical response, and survival [9][10][11][12][13][14][15][16]. During an unprecedented time when proven effective therapies remain lacking, we aimed to describe our experience using off-label tocilizumab for COVID-19.…”

Pulmonary Cavitation – An Under-recognized Late Complication of Severe COVID-19 Lung Disease

“…Recently it has been associated with improved survival in patients with severe COVID-19 pneumonia with evidence of CRS. 15,16 In general tocilizumab is well tolerated but can induce neutropenia, and an increased risk of developing infections has been reported. 17,18 Furthermore, it may predispose to a delay in detecting active infection because of the masking effect of a suppressed C reactive protein (CRP) response.…”

Role of interleukin 6 as a predictive factor for a severe course of Covid-19: retrospective data analysis of patients from a Long-term Care Facility during Covid-19 Outbreak

“…This dysregulation is characterized by high production of proin ammatory cytokines by monocytes and macrophages and CD4 lymphocyte depletion that contributes to the progression of in ammation of lung parenchyma [19]. The direct role of IL-6 in Covid-19 pathogenesis is further supported by ndings that IL-6 inhibition improves the prognosis of severe Covid-19 [27,25].…”