Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab

Annette Langer-Gould, Jessica B Smith, Edlin G Gonzales, Rhina D Castillo, Judith Garza Figueroa, Anusha Ramanathan, Bonnie H Li, Michael K Gould, Annette Langer-Gould, Jessica B Smith, Edlin G Gonzales, Rhina D Castillo, Judith Garza Figueroa, Anusha Ramanathan, Bonnie H Li, Michael K Gould

Abstract

Objective: To examine outcomes among patients who were treated with the targeted anti-cytokine agents, anakinra or tocilizumab, for COVID-19 -related cytokine storm (COVID19-CS).

Methods: We conducted a retrospective cohort study of all SARS-coV2-RNA-positive patients treated with tocilizumab or anakinra in Kaiser Permanente Southern California. Local experts developed and implemented criteria to define COVID19-CS. All variables were extracted from electronic health records.

Results: At tocilizumab initiation (n = 52), 50 (96.2%) were intubated, and only seven (13.5%) received concomitant corticosteroids. At anakinra initiation (n = 41), 23 (56.1%) were intubated, and all received concomitant corticosteroids. Fewer anakinra-treated patients died (n = 9, 22%) and more were extubated/never intubated (n = 26, 63.4%) compared to tocilizumab-treated patients (n = 24, 46.2% dead, n = 22, 42.3% extubated/never intubated). Patients who died had more severe sepsis and respiratory failure and met COVID-CS laboratory criteria longer (median = 3 days) compared to those extubated/never intubated (median = 1 day). After accounting for differences in disease severity at treatment initiation, this apparent superiority of anakinra over tocilizumab was no longer statistically significant (propensity score-adjusted hazards ratio 0.46, 95% confidence interval 0.18-1.20).

Conclusions: Prompt identification and treatment of COVID19-CS before intubation may be more important than the specific type of anti-inflammatory treatment. Randomized controlled trials of targeted anti-cytokine treatments and corticosteroids should report the duration of cytokine storm in addition to clinical severity at randomization.

Keywords: Anakinra; COVID-19; Corticosteroids; Cytokine storm; Tocilizumab.

Copyright © 2020 Southern California Permanente Medical Group. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1
Figure 1
Clinical Outcomes among COVID-19 patients treated with Tocilizumab or Anakinra. Fewer tocilizumab (toci, in blue) showed significant clinical improvement (Toci Responders) compared to anakinra-treated patients (Ana Responders, in green). Among the 18 non-intubated patients at anakinra start, 14 never required intubation, three were subsequently intubated (one extubated and two still intubated), and one elderly man was not intubated in accordance with his family’s wishes and died. Among intubated patients, those that showed the type of rapid improvement (extubation within seven days, 7d) expected based on the treatment of non−COVID-related cytokine storm, is similar across treatment groups. COVID-19=coronavirus 2019.
Figure 2
Figure 2
Survival Among Anakinra or Tocilizumab-treated COVID-19 Patients. Depicted is the Kaplan-Meier survival curve of patients treated with anakinra (n = 41, blue) or tocilizumab (n = 52, red line) up to 30 days after receiving their first dose. COVID-19=coronavirus 2019.

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Source: PubMed

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