We read with interest the Article by Thomas Huet and colleagues1 that shows an association between anakinra use and reduced need for invasive mechanical ventilation in an intensive care unit and mortality in patients with severe forms of COVID-19, without serious side-effects.
The authors should be applauded; however, we would like to highlight some important limitations. First, looking at the Kaplan-Meier curves, there is an immediate drop in the historical control group suggesting that some of the patients were either already receiving mechanical ventilation in the intensive care unit when they met the inclusion criteria (one patient was already dead at time zero) or they developed the event on the same day they met the inclusion criteria, thereby biasing the effect estimate in favour of anakinra group.
Second, although authors have stated the time zero for the anakinra group, the same has not been done for the historical group. The historical group was selected retrospectively based on time varying inclusion and exclusion criteria, which could have led to sicker patients in this group.
Third, using oxygen saturation as a criterion for inclusion might not reveal an adequate spectrum of disease severity compared with other variables, such as the partial pressure of arterial oxygen to percentage of inspired oxygen ratio.
Fourth, the 73% of patients in the historical group requiring invasive mechanical ventilation or dying is not consistent with the available literature. Mortality estimates, published in 2020, from various cohorts range between 16% and 45%.2, 3
Finally, hydroxychloroquine was significantly more commonly used in the anakinra group compared with the historical control group. Although the authors mention that the results remain unchanged after multivariable analysis, the possibility of baseline confounding cannot be ruled out.
We would like the authors to reanalyse the data in the presence of above limitations before any conclusions are drawn from this study.
Acknowledgments
We declare no competing interests.
References
- 1.Huet T, Beaussier H, Voisin O. Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol. 2020;2:e393–e400. doi: 10.1016/S2665-9913(20)30164-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
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