Tocilizumab in COVID-19 interstitial pneumonia

Abstract

Background: Published reports on tocilizumab in COVID-19 pneumonitis show conflicting results due to weak designs or heterogeneity in critical methodological issues.

Methods: This open-label trial, structured according to Simon's optimal design, aims to identify factors predicting which patients could benefit from anti-IL6 strategies and to enhance the design of unequivocal and reliable future randomized trials. A total of 46 patients with COVID-19 pneumonia needing of oxygen therapy to maintain SO2 > 93% and with recent worsening of lung function received a single infusion of tocilizumab. Clinical and biological markers were measured to test their predictive values. Primary end point was early and sustained clinical response.

Results: Twenty-one patients fulfilled pre-defined response criteria. Lower levels of IL-6 at 24 h after tocilizumab infusion (P = 0.049) and higher baseline values of PaO2/FiO2 (P = 0.008) predicted a favourable response.

Conclusions: Objective clinical response rate overcame the pre-defined threshold of 30%. Efficacy of tocilizumab to improve respiratory function in patients selected according to our inclusion criteria warrants investigations in randomized trials.

Keywords: COVID-19; IL-6; pneumonia; severe acute respiratory syndrome; tocilizumab.

Fig. 1

Upper normal limits of reference range at Ospedali Riuniti (Ancona) were IL‐6: 5.2 pg mL⁻¹, thrombomodulin 11.2 ng mL⁻¹ and SP‐D 190 ng mL⁻¹; Using Mann–Whitney's U test; P‐value Il‐6 in responder vs non responder was 0.020, 0.001 and <0.001 at baseline, 24 and 72 h after infusion, respectively. Samples for IL‐6 at baseline were available in 36 patients, 40 patients at 24 h, and 35 patients at 72 h; vWf and thrombomodulin were tested 30 patients and for vWF in 20 normal controls; S‐PD was tested in 20 patients.