medwireNews: Treatment with the interleukin (IL)-1 receptor antagonist anakinra may reduce mortality risk versus standard care in people with moderate-to-severe COVID-19, particularly those with hyperinflammation, suggests a systematic review and patient-level meta-analysis.
Evangelos Giamarellos-Bourboulis (ATTIKON University Hospital, Athens, Greece) and co-investigators reviewed aggregate data for 1185 patients from nine studies who required oxygen supplementation for COVID-19 but were not yet receiving organ support.
Of these, 509 were given anakinra and 676 received usual care with or without placebo.
The researchers report in The Lancet Rheumatology that individuals receiving anakinra had a significant 63% lower risk for death at 28 days than those receiving usual care.
Further analysis of individual patient-level data on 895 patients from six studies showed that anakinra use was associated with a significant 68% lower risk for death versus no use, after adjustment for age, comorbidity, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen, C-reactive protein (CRP) concentration, and lymphopenia.
Specifically, the 28-day mortality rate was 11% among the 342 patients who received anakinra versus 25% among the 553 who did not.
Subgroup analyses revealed that the impact of anakinra varied significantly by baseline CRP level. Individuals with CRP concentrations above 100 mg/L had a significant 72% lower risk for death with versus without anakinra therapy, whereas those with lower baseline CRP levels had a nonsignificant 33% reduced mortality risk.
There was also a difference in treatment response between patients who had and had not received cotreatment with dexamethasone. In this case, there was a significant survival benefit when anakinra was given without dexamethasone, at an odds ratio (OR) of 0.23, but not when given alongside the corticosteroid (OR=0.72).
Rachel Tattersall (Sheffield Teaching Hospitals NHS Foundation Trust, UK) and colleagues remark on this finding in an accompanying comment. They ask: “If the absence of additional benefit of anakinra in patients treated with dexamethasone was to be prospectively confirmed, what is the role of this costly and limited-availability drug in a global pandemic?”
The commentators suggest: “It might be that there is a place for anakinra in specific patient groups to enable steroid-minimised treatment regimens, given the worrying reports of increased complications in people with diabetes treated with dexamethasone and the rise of previously rare infections such as mucormycosis.”
Of note, Giamarellos-Bourboulis and co-authors found that the impact of anakinra on mortality risk was similar in people with and without diabetes, with significant risk reductions of 60% and 63%, respectively.
They also report that there was no significantly increased risk for secondary infections with anakinra use, but the rates of elevated liver enzymes and leukopenia were a nonsignificant three to four times higher with versus without the IL-1 receptor agonist.
The team concludes: “Larger trials are ongoing, and their results are urgently needed to further investigate the most effective use of anakinra in the treatment of COVID-19.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group
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Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00216-2
Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00249-6