Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia

Abstract

Background: Pneumonia with respiratory failure represents the main cause of death in COVID-19, where hyper inflammation plays an important role in lung damage. This study aims to evaluate if tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, reduces patients' mortality. Methods: 85 consecutive patients admitted to the Montichiari Hospital (Italy) with COVID-19 related pneumonia and respiratory failure, not needing mechanical ventilation, were included if satisfying at least one among: respiratory rate ≥ 30 breaths/min, peripheral capillary oxygen saturation ≤ 93% or PaO2/FiO2<=300 mmHg. Patients admitted before March 13th (n=23) were prescribed the standard therapy (hydroxychloroquine, lopinavir and ritonavir) and were considered controls. On March 13th tocilizumab was available and patients admitted thereafter (n=62) received tocilizumab once within 4 days from admission, plus the standard care. Results: Patients receiving tocilizumab showed significantly greater survival rate as compared to control patients (hazard ratio for death, 0.035; 95% confidence interval [CI], 0.004 to 0.347; p = 0.004), adjusting for baseline clinical characteristics. Two out of 62 patients of the tocilizumab group and 11 out of 23 in the control group died. 92% and 42.1% of the discharged patients in the tocilizumab and control group respectively, recovered. The respiratory function resulted improved in 64.8% of the observations in tocilizumab patients who were still hospitalized, whereas 100% of controls worsened and needed mechanical ventilation. No infections were reported. Conclusions: Tocilizumab results to have a positive impact if used early during Covid-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course.

Impact of Corticosteroids and Immunosuppressive Therapies on Symptomatic SARS-CoV-2 Infection in a Large Cohort of Patients with Chronic Inflammatory Arthritis

“…The improvement in knowledge on COVID-19related ARDS pathogenesis has pointed out the central role of the abnormal immune response to SARS-CoV-2 leading to a massive release of pro-in ammatory mediators known as cytokine release storm [52,53]. This has actually paved the way for the use of biological drugs and small molecules in the treatment of the most severe subsets of COVID-19 [13,[54][55][56][57][58][59]. Although the apparent bene cial therapeutic effects of immunomodulatory agents cannot be translated into any speculation on their prophylactic role, the possibility that chronic use of ts/bDMARDs may dampen exaggerated immune reactions, thus mitigating COVID-19 progression into more symptomatic patterns, deserves further investigation.…”

Efficacy and safety of tocilizumab in COVID-19 patients: A Meta-Analysis

“…Thus, 28 articles included 991 COVID-19 patients underwent tocilizumab administration were included in this study 10,11, . Of the 28 included studies, 7 of which included 377 patients were case-control studies with a control group not using tocilizumab 28,29,32,36,39,40,42 .…”

“…Data were unavailable for mortality in 3 studies, and a pooled all-cause death rate of 16% (95% CI, 11-22%; I 2 = 67%, P< 0.0001) was reported in 870 patients when treated with tocilizumab. 17 studies 10,11,19,[21][22][23][25][26][27][28][29]31,33,[35][36][37]40 comprising 562 patients were de ned as severe COVID-19 infection, and the pooled ORR of treatment with tocilizumab was 78% (95% CI, 70-85%; I 2 = 65%, P< 0.0001), while pooled ORR in 64 nonsevere infection was 93% (95% CI, 85-98%; I 2 = 0%, P=0.66) ( Figure S2).…”

“…At the point of study completion, median LOH and LOI was 14 days (range 11-34) and 8 days (range [5][6][7][8][9][10][11] in patients receiving tocilizumab, which was speci ed in 15 studies 10,[20][21][22][23]28,29,31,32,35,36,[38][39][40][41] and 8 studies 10,23,27,29,32,33,36,42 , separately. Moreover, the median duration of mechanical ventilation was 7 days (range 5-10) after treatment of tocilizumab which was documented in 9 articles 10,11,[21][22][23]27,28,40,41 ( Table 2).…”

Matched Cohort Study on the Efficacy of Tocilizumab in Patients with COVID-19&nbsp;

“…However, e cacy of tocilizumab in COVID-19 disease, has yet to be demonstrated. To date no results from randomized clinical trials testing tocilizumab have been reported and, the few observational studies which has a comparative group, report con ictive results on mortality or clinical improvement (6)(7)(8)(9).…”