Systematic Review and Subgroup Meta-analysis of Randomized Trials to Determine Tocilizumab’s Place in COVID-19 Pneumonia

Klopfenstein, Timothée; Gendrin, Vincent; Gerazime, Aurélie; Conrozier, Thierry; Balblanc, Jean-Charles; Royer, Pierre-Yves; Lohse, Anne; Mezher, Chaouki; Toko, Lynda; Guillochon, Cerise; Badie, Julio; Pierron, Alix; Kadiane-Oussou, N.’dri Juliette; Puyraveau, Marc; Zayet, Souheil

INTRODUCTION: Tocilizumab randomized clinical trial results are heterogeneous because of the heterogenous population included in them. METHODS: We conducted a meta-analysis with subgroup meta-analysis (PRISMA guidelines) between severe and non-severe COVID-19. RESULTS: We included nine trials. Overall, the mortality rate was 24.5% (821/3357) in the tocilizumab group and 29.1% (908/3125) in the control group at day 28–30 (pooled OR, 0.85; 95% CI 0.76–0.96; p = 0.006). Considering the subgroup analysis, this benefit on mortality was confirmed and amplified in the severe COVID-19 group (pooled OR, 0.82; 95% CI 0.73–0.93; p = 0.001) but not in the non-severe COVID-19 group (pooled OR, 1.46; 95% CI 0.91–2.34; p = 0.12). For patients who were not mechanically ventilated at baseline (5523/6482), the pooled OR (0.74; 95% CI 0.64–0.85; p < 0.0001) for mechanical ventilation incidence at day 28–30 was in favor of tocilizumab (cumulative incidence of 14.8% versus 19.4% in tocilizumab and control arm, respectively). This benefit was confirmed in both subgroups, i.e., severe and non-severe COVID-19. CONCLUSION: Tocilizumab is an effective treatment in hospitalized patients with COVID-19 and hypoxemia by improving survival and decreasing mechanical ventilation requirement. The greatest benefit is observed in severe COVID-19.