Anakinra and Intravenous IgG versus Tocilizumab in the Treatment of COVID-19 Pneumonia

Abstract

Background: COVID-19 can lead to acute respiratory failure and an exaggerated inflammatory response. Studies have suggested promising outcomes using monoclonal antibodies targeting IL-1β (Anakinra) or IL6 (Tocilizumab), however no head to head comparison was done between the two treatments. Herein, we report our experience in treating COVID-19 pneumonia associated with cytokine storm with either subcutaneous Anakinra given concomitantly with intravenous immunoglobulin (IVIG), or intravenous Tocilizumab. Methods: Comprehensive clinical and laboratory data from patients with COVID-19 pneumonia admitted at our hospital between March and May 2020 were collected. Patients who received either Anakinra/ IVIG or Tocilizumab were selected. Baseline characteristics including oxygen therapy, respiratory status evaluation using ROX index, clinical assessment using NEWS score and laboratory data were collected. Outcomes included mortality, intubation, ICU admission and length of stay. In addition, we compared the change in ROX index, NEWS score and inflammatory markers at days 7 and 14 post initiation of therapy. Results: 84 consecutive patients who received either treatment (51 in the Anakinra/ IVIG group and 33 in the Tocilizumab group) were retrospectively studied. Baseline inflammatory markers were similar in both groups. There was no significant difference regarding to death (21.6% vs 15.2%, p 0.464), intubation (15.7% vs 24.2%, p 0.329), ICU need (57.1% vs 48.5%, p 0.475) or length of stay (13+9.6 vs 14.9+11.6, p 0.512) in the Anakinra/IVIG and Tocilizumab, respectively. Additionally, the rate of improvement in ROX index, NEWS score and inflammatory markers was similar in both groups at days 7 and 14. Furthermore, there was no difference in the incidence of superinfection in both groups. Conclusion: Treating COVID-19 pneumonia associated with cytokine storm features with either subcutaneous Anakinra/IVIG or intravenous Tocilizumab is associated with improved clinical outcomes in most subjects. The choice of treatment does not appear to affect morbidity or mortality. Randomized controlled trials are needed to confirm our study findings. Funding: None.

Intravenous immunoglobulin immunotherapy for coronavirus disease‐19 (COVID‐19)

“…Currently, data are available from seven reports including the multicentre study of Shao et al that explored IVIG immunotherapy in the management of COVID-19 (Table 1). [5][6][7][8][9][10][11] These studies are mostly case series or retrospective, with an exception of one study that was randomised open-label trial. Although retrospective, data from Shao et al included large number of COVID-19 patients compared to other studies, and hence, data are more reliable.…”

“…Another study combined IVIG with anakinra, a recombinant modified IL-1 receptor antagonist. 11 Thus, in view of associated therapies, the therapeutic benefits of IVIG have to be evaluated carefully. It is important to note that studies in autoimmune and inflammatory diseases have reported better outcomes if IVIG is combined with steroids.…”

“…that explored IVIG immunotherapy in the management of COVID‐19 (Table 1). 5–11 These studies are mostly case series or retrospective, with an exception of one study that was randomised open‐label trial. Although retrospective, data from Shao et al .…”

“…In view of the corticosteroid combination, it is difficult to evaluate the therapeutic benefits of IVIG in these trials. Another study combined IVIG with anakinra, a recombinant modified IL‐1 receptor antagonist 11 . Thus, in view of associated therapies, the therapeutic benefits of IVIG have to be evaluated carefully.…”

What's new in critical illness and injury science? Intravenous immunoglobulin for COVID-19 with severe or critical illness

“…The second, a randomized study preprint, was excluded because it compared two experimental therapies (Anakinra/IVIG vs. Tocilizumab) without a control or usual care arm. [ 28 ] Finally, a nonrandomized study that compared early (<48 h) to late (≥48 h) IVIG treatment for COVID-19 was excluded because there was no non-IVIG treatment or usual care arm. [ 26 ] The risk of bias was assessed for each study using the ROBINS-I and GRADE tools.…”