Factors for decision making
No studies were found considering the effectiveness, safety or cost effectiveness of anakinra in adults and children with sHLH triggered by SARS-CoV-2 or a similar coronavirus.
No published evidence was found to support using anakinra for COVID-19 associated sHLH. However, 2 preprints were identified. Preprints are preliminary reports of work that have not yet undergone peer review and should be considered unpublished. Preprints are usually submitted to a preprint server before or at the same time they are submitted for publication to a peer-reviewed journal. The findings reported in the preprint therefore need to be interpreted with caution and should not be reported as established information.
The first preprint was the PROSPERO systemic review (Khan et al. 2020). This systematic review did not identify any published studies of anakinra. The second preprint was a small study (Dimopoulos et al. 2020) that included 8 people with severe COVID-19 pneumonia and sHLH who were treated with anakinra. At the end of treatment with anakinra, the authors report that laboratory outcomes were improved, as was the patients' respiratory function. Two patients died. The authors conclude that anakinra may be a viable treatment for severe COVID-19 associated sHLH and note that larger clinical studies are needed to validate this concept.
A small retrospective cohort study was published after the searches for the evidence review were undertaken (Cavalli et al. 2020). It looked at the effects of anakinra in people with COVID-19, moderate to severe ARDS and hyperinflammation but hyperinflammation in the study population was not defined in the same way as sHLH (La Rosee et al. 2019).
The study found that, at 21 days, survival was 90% (26/29) in the high-dose intravenous anakinra group (5 mg/kg twice daily, median treatment duration 9 days) and 56% (9/16) in the standard treatment group (p=0.009). High-dose anakinra was discontinued because of adverse effects in 24% (7/29) of patients. Bacteraemia occurred in 14% (4/29) of patients receiving anakinra and 13% (2/16) of patients receiving standard treatment (p value not reported). The study by Cavalli et al. has many limitations and should be considered hypothesis-generating only.
Many trials are planned or underway to assess anakinra for treating symptoms associated with SARS-CoV-2, including several for cytokine storm syndromes and hyperinflammation, including sHLH. Primary completion is expected for the earliest of these in July 2020 (Sobi.IMMUNO-101, NCT04324021 and Chatham-Cytokine Covid-19, NCT04362111).
Anakinra has been used (off label) for cytokine storm syndromes triggered by other viruses (such as herpes viruses), including sHLH, and is reported to be relatively well tolerated, with a favourable safety profile. Caution is advised when using immunomodulating therapies in critically ill people with known or suspected infections because they increase the risk of infectious complications. However, it has been proposed that anakinra may be an option if such a treatment is considered necessary because it has a relatively short half-life and can be discontinued quickly if an adverse effect or concern for worsening infection arises (Wampler Muskardin et al. 2020). Anakinra can be given intravenously (off label) or subcutaneously and has a large therapeutic window. When anakinra is effective for cytokine storm syndromes, it reportedly works within 2 or 3 days (Cron et al. 2020).
See the full evidence review for more information.
Commissioned by NHS England