An anti-inflammatory drug used to treat rheumatoid arthritis has been reported by some news sources to be a potentially ‘life-saving coronavirus treatment.’

Growing evidence suggests that some of the severe effects seen in COVID-19 could be caused by an excessive inflammatory response known as a ‘cytokine storm’.  Anakinra is a drug that blocks the action of a cytokine called interleukin-1. It has been used before to treat cytokine storms caused by other conditions, but it is not licensed for this use.

The recent news reports were prompted by a French cohort study which used anakinra to treat 52 people hospitalised with severe COVID pneumonia. Over two weeks of treatment, only 25% of those receiving anakinra needed ventilation or died, compared with 73% of similar patients who had recently been treated in the same hospital, but who didn’t receive anakinra. People taking anakinra were slightly more likely to develop blood clots and liver imbalance.

The drug seems to show promise for severe COVID pneumonia in this early stage research, but more research is needed. Several randomised controlled trials are currently in progress that will allow us to reach more definitive conclusions about anakinra’s impact.

Where did the story come from?

The Telegraph is among media sources to have reported on the cohort study carried out by researchers from Hôpital Paris Saint-Joseph in France, and published in the peer-reviewed journal The Lancet.

A cohort study compares outcomes in groups of people being treated in different ways. The main limitation of this type of study is that differences between the groups other than the treatments being received could impact their outcomes.

What is the basis for the claim?

The cohort study recruited adults who were admitted with severe pneumonia in both lungs due to COVID-19. Patients who agreed to be given anakinra received injections of the drug for 10 days. In total 52 patients were recruited to receive anakinra between 24th March and 6th April.

As a control group, the researchers identified 44 patients admitted with COVID-19 earlier in  March who had the same symptoms but had not received anakinra. These patients received other treatments being used at the hospital at the time, including antibiotics or the antimalarial hydroxychloroquine. All patients received anti-clotting drugs.

Over two weeks, three-quarters of the control group (32/44) required ventilation or died compared with only 25% in the anakinra group (13/52). After considering known differences between the groups, this represented a 78% reduction in risk of death or needing ventilation with anakinra.

More patients in the anakinra group developed a blood clot (19% versus 11% of controls) or had elevated levels of certain liver enzymes (13% versus 9%). None of the patients in the anakinra group developed bacterial infections while they were in hospital.

In addition to this study, there have been a few other small observational studies on the use of anakinra in COVID-19, some of which have not been fully published or peer reviewed. At this stage, their limitations mean that strong conclusions can’t be drawn. However, they do suggest that more robust trials are worth conducting, and there are reportedly 10 such clinical trials currently in progress, including one in the UK. Most of these are due to be completed later this year.

These trials are looking at different types of patients and doses of anakinra, they are also comparing anakinra to different treatments and looking at different outcomes. As well as looking at potential benefits, these trials will also closely consider whether anakinra could cause harm. This is important as anakinra is known to lower white blood cell count and increase risk of infection.

The results of these trials will give greater certainty of the effect of anakinra and which patient groups could most benefit from treatment.

What do trusted sources say?

In standard medical practice, anakinra has strict criteria for use, which are laid out in the drug’s licence. In Europe and the US for example, it is only licensed as a second-line treatment for rheumatoid arthritis, and for a few other less common conditions. Its current use in the treatment of COVID-19 is ‘off label’ meaning it is not currently licensed for that use.

In May the UK’s National Institute for Health and Care Excellence (NICE) reviewed the evidence on the use of anakinra in people with a specific inflammatory syndrome resulting from COVID-19 in May. At that point, they only identified three small observational studies in people with COVID-19, only one of which was published.

NICE says that anakinra has been used off label for cytokine storms triggered by other viruses and is reported to be relatively well tolerated. However, they advised caution in using anakinra and other drugs which affect the immune system in critically ill people with known or suspected infections because they increase the risk of infectious complications.

Analysis by EIU healthcare, supported by RB

 

Citation

  1. Huet T, Beaussier H, Voisin O, et al. Anakinra for severe forms of COVID-19: a cohort study. The Lancet Rheumatology. 2020 May 29.
  2. King A, Vail A, O’Leary C, Hannan C, et al. Anakinra in COVID-19: important considerations for clinical trials. The Lancet Rheumatology. 2020 May 21.

Further reading

  1. NICE. COVID 19 rapid evidence summary: Anakinra for COVID-19 associated secondary haemophagocytic lymphohistiocytosis. 21 May 2020. (Accessed 8 June 2020)
  2. European Medicines Agency. Kineret (anakinra). (Accessed 8 June 2020)