ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 Patients

  1. Eleni Karakike
  2. George N. Dalekos
  3. Ioannis Koutsodimitropoulos
  4. Maria Saridaki
  5. Chryssa Pourzitaki
  6. Georgios Papathanakos
  7. Antigone Kotsaki
  8. Stamatios Chalvatzis
  9. Vasiliki Dimakopoulou
  10. Nikolaos Vechlidis
  11. Elisabeth Paramythiotou
  12. Christina Avgoustou
  13. Aikaterini Ioakeimidou
  14. Elli Kouriannidi
  15. Apostolos Komnos
  16. Evangelia Neou
  17. Nikoletta Rovina
  18. Eleni Stefanatou
  19. Haralampos Milionis
  20. George Nikolaidis
  21. Antonia Koutsoukou
  22. Georgia Damoraki
  23. George Dimopoulos
  24. Vassileios Zoumpos
  25. Jesper Eugen-Olsen
  26. Karolina Akinosoglou
  27. Nikolaos K. Gatselis
  28. Vasilios Koulouras
  29. Eleni Gkeka
  30. Nikolaos Markou
  31. Mihai G. Netea
  32. Evangelos J. Giamarellos-Bourboulis
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Abstract

Rationale

Macrophage activation syndrome (MAS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19.

Objective

To investigate the outcome of personalized immunotherapy in critical COVID-19.

Methods

In this open-label prospective trial, 102 patients with SOFA (sequential organ failure assessment) score ≥2 or ARDS by SARS-CoV-2 were screened for MAS (ferritin more than 4420 ng/ml) and CID (ferritin ≤4420 ng/ml and low expression of HLA-DR on CD14-monocytes). Patients with MAS and CID with increased aminotransferases were assigned to intravenous anakinra; those with CID and normal aminotransferases to tocilizumab. The primary outcome was at least 25% decrease of SOFA score and/or 50% increase of respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28; serum biomarkers and cytokine production by mononuclear cells were secondary endpoints.

Measurements and Main Results

The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (odds ratio 3.11; 95% CIs 1.29-7.73; P: 0.011). No differences were found in mortality and in SOFA score changes. By day 4, ferritin was decreased among anakinra-treated patients; interleukin (IL)-6, soluble urokinase plasminogen activator receptor (suPAR) and the expression of HLA-DR were increased among tocilizumab-treated patients. Anakinra increased capacity of mononuclear cells to produce IL-6. Survivors by day 28 who received anakinra were distributed to scales of the WHO clinical progression of lower severity. Greater incidence of secondary infections was found with tocilizumab treatment.

Conclusions

Biomarkers may guide favourable anakinra responses in critically ill patients with COVID-19.

Trial Registration

ClinicalTrials.gov, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04339712">NCT04339712</ext-link>

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