Anakinra 

Treatment with anakinra (either 5 mg/kg twice a day intravenously [high dose] or 100 mg twice a day subcutaneously [low dose]) was safe and associated with clinical improvement in 72% of patients. Used in combination with 200 mg hydroxychloroquine twice a day orally and 400 mg lopinavir with 100 mg ritonavir twice a day orally.

Significant reduction in mortality or need of invasive mechanical ventilation without serious side-effects. Sample size: 52 + 44 control. Dosage: subcutaneously 100 mg twice daily on days 1-3, 100 mg daily on days 4-10.

Possible clinical improvement in some patients. Significant reduction of CRP, IL-6 and ferritin levels. Sample size: 9 + 18 tocilizumab control. Dosage: 100 mg every 6 h for at least 3 days. Afterwards, dosage reduced to every 24 h in some patients. Up to 7 days. Endpoint: Progressive resolution of ARDS.

Rapid reduction of inflammation and enabling of extubation in an ARDS patient with cytokine release syndrome upon low-dose treatment.

Clinical improvement (increased oxygenation, reduced inflammation) upon treatment with anakinra in a patient with ARDS. Dosage: 150 mg twice daily for 7 days.

Clinical (ventilatory and inotropic support) and biochemical (inflammatory markers) improvement. Sample size: 4. Dosage: 200 - 300 mg once to twice daily.

Significantly lower rate of mechanical ventilation need, higher proportion of patients that ceased to be dependent on supplemental oxygen, and improvement in inflammatory markers. Mortality percentage in the treatment group was lower but without statistical significance.

In combination with methylprednisolone. The treatment group patients with COVID-19-linked hyperinflammation were in a significantly lower adjusted and unadjusted risk of death compared to a historical control. Sample size: 65 + 55 control. Dosage: Subcutaneous (IV in mechanical ventilation patients) dose of 200 mg every 8 hours on days 1-3; 100 mg every 8 hours on days 4-14. Endpoint: 28-day mortality.

In combination with dexamethasone. Rapid clinical improvement in a COVID-19 patient with acute respiratory failure and cardiogenic shock. Dosage: 100 mg twice daily.

Clinical improvement (suppresion of inflammation) after anakinra treatment. Bacterial superinfection (managable) occurred, however. Dosage: 100 mg subcutaneous injection daily; total of 9 doses over 12 days.

In some patients with severe COVID-19 pneumonia and moderate hyperinflammation who did not respond to corticosteroid treatment with or without tocilizumab administration, anakinra treatment could prevent death and result in clinical improvement. Sample size: 10 (anakinra, corticosteroids, and tocilizumab (optional)) + 59 (corticosteroids and tocilizumab) + 74 (corticosteroids). Dosage: 100 mg every 12 hours (50–60 kg body weight), every 8 hours (60–75 kg), or every 6 hours (>75 kg) on day 1; 100 mg twice a day on days 2–6. Endpoint: Death and ICU admission rate within 60 days of the first corticosteroid pulse.

Statistically significant improvement in 28-day survival in COVID-19 ARDS patients treated with anakinra compared to control. The medication was well-tolerated. Sample size: 56 + 56 control. Dosage: 100 mg subcutaneously four times a day (non-ICU) or 200 mg IV three times a day (ICU) for 7 days. Primary endpoint: Survival at day 28.

Efficacy of early anti-inflammatory treatment with high doses IV Anakinra with or without

Clinical improvement was observed upon anakinra administration in 2 paediatric patients suffering from COVID-19-related Multisystem Inflammatory Syndrome who have not sufficiently responded to previous

Anakinra treatment was initiated in the study group upon ≥6 ng/ml concentration of soluble urokinase plasminogen activator receptor was reached (suPAR). suPAR is an early predictor of progression into severe respiratory failure (SRF) in COVID-19 patients. The incidence of SRF in the treatment group was 70% lower compared to the control group (the difference was statistically significant). This also led to improvement in inflammation markers and in the function of peripheral blood mononuclear cells, better clinical score, lower 30- and 90-day mortality and lower overall hospitalization costs. Incidence of adverse effects was similar in both groups, except for leukopenia, which was more prevalent in the anakinra treatment group. Severe adverse events were less frequent in the anakinra treatment group. Sample size: 130 + 130 matched control (standard of care). Dosage: 100mg subcutaneously once a day for 10 days. Primary outcome: Severe respiratory failure incidence by day 14.

The clinical status of an elderly patient improved after anakinra administration. The bilirubin levels were elevated 5 days after the treatment, however. Sample size: 1. Dosage: For 5 days. 

Hyper-inflammation was suppressed after anakinra treatment initiation. Sample size: 1. Dosage: 200 mg IV, then subcutaneously 100 mg every 6 hours. 

COVID-19-associated pericarditis and inflammation were successfully treated using anakinra. Sample size: 1. Dosage: 100 mg daily for 14 days. 

Data suggest that anakinra might be effective in paediatric patients witch COVID=19-related multisystem inflammatory syndrome who do not respond to intravenous immunoglobulins and corticosteroids. Sample size: 2. Dosage: 5 or 6 mg/kg a day in two doses. 

All but one patient experienced a decrease in inflammation markers and improvement in clinical status upon anakinra administration. Sample size: 4. Dosage: 5 or 10 mg/kg or 400 mg daily for 10 to 26 days. 

Clinical and radiological improvement were observed. Sample size: 1. Dosage: Subcutaneously 100 mg every 6 hours on days 1–10, every 8 hours on days 11–14. 

A patient with multisystem inflammatory syndrome related to COVID-19 was successfully treated with the use of anakinra. Sample size: 1. 

Early anakinra administration was associated with lower ICU admission rate and mortality. Sample size: 119. Dosage: A mean daily dose of 272.2 mg. 

At the end of anakinra treatment in patients with severe COVID-19 and secondary hemophagocytic lymphohistiocytosis, respiratory function was improved. Three of the patients died; nevertheless, such mortality is lower compared to historical series of patients with similar diagnoses. Sample size: 8. Dosage: 200 mg IV every 8 hours for 7 days or 300 mg once daily for 4 days. 

Early administration of anakinra generally led to a favourable clinical outcome. Sample size: 11 + 3 control. Dosage: Subcutaneously 100 mg every 6 hours with a gradual decrease in administration frequency; maximum of 20 days (2 patients initially with lower dosing). 

A statistically significant reduction in markers of hyperinflammation was observed in the treated cohort. No differences in duration of mechanical ventilation or ICU length of stay compared to control was observed, however. Sample size: 21 + 39 control. Dosage: 300 mg loading dose and then 100 mg IV every 6 hours. Main outcome: Inflammatory response parameters.

A patient with multisystem inflammatory syndrome related to COVID-19 was successfully treated using anakinra. Sample size: 1. Dosage: 100 mg every 48 hours (due to renal insufficiency). 

A generally good clinical outcome was observed in pregnant patients with COVID-19 treated using anakinra and methylprednisolone. Sample size: 14. Dosage: 400 mg (median) on day 1, followed by 2–10 mg/kg in divided doses every 6 hours; median duration of 6 days. 

The treatment reduced the length of hospital stay and the need for invasive mechanical ventilation. Sample size: 15 + 15 control. Dosage: 100 mg IV daily for 14 days or until hospital discharge. Main outcome: The need for endotracheal intubation.

The treated patients showed good clinical outcomes. The treatment was safe. Sample size: 9 (in 1 of which the treatment was prematurely stopped). Dosage: Subcutaneously 100 mg twice a day on days 1–3, once a day on days 4–10. 

A combined treatment using anakinra and ruxolitinib led to clinical improvement and survival of 10 out of 11 critically ill patients. Sample size: 11. Dosage: 300 mg daily for 11 days, then tapered until day 14; a mean total dose of 3800 mg. 

Administration of anakinra and remdesivir led to radiological and clinical improvement in a severe COVID-19 patient. Sample size: 1. Dosage: 100 mg subcutaneously every 6 hours for 7 days. 

Rapid clinical improvement, including resolution of systemic inflammation, was observed after administration of the drug. Sample size: 5. Dosage: 100 mg every 8 hours during 24–48 hours followed by dose de-escalation. 

Treatment of a child with multisystem inflammatory syndrome related to COVID-19 with anakinra led to clinical improvement and a full recovery. Sample size: 1. Dosage: 8 mg/kg daily. 

The treatment led to a favourable outcome. Sample size: 1. Dosage: A single dose of 100 mg subcutaneously. 

The early treatment of COVID-19 pneumonia patients using anakinra (with or without corticosteroids) seems to be safe and efficacious. Sample size: 63 (early anakinra with or without corticosteroids) + 65 control (late anti-inflammatory treatment). Dosage: 100 mg every 8 hours for 3 days followed by tapering (maximum total of 9 days). Main outcome: Overall survival.

The treatment with anakinra in acute leukaemia patients with COVID-19-related pneumonia was safe and led to clinical improvement. Sample size: 3. Dosage: 100 mg three times a day or 200 mg twice a day followed by dose de-escalation upon clinical improvement. 

Adolescent patients were successfully treated with methylprednisolone and anakinra upon worsening of COVID-19 symptoms (including systemic inflammation). Sample size: 2. Dosage: 6–8 mg daily IV. 

Early treatment using anakinra, guided by soluble urokinase plasminogen activator receptor serum levels, resulted in significantly lower odds of clinical deterioration, higher median clinical improvement, decreased mortality, and shorter hospital/ICU stay. Sample size: (intention-to-treat) 405 + 189 placebo. Dosage: 100 mg subcutaneously once a day for 7–10 days. Main outcome: Safety and efficacy on an ordinal scale on day 28 from the treatment initiation.

In this series of patients with pulmonary fibrosis and hypoxaemia, anakinra displayed promising efficacy even when administrate later after clinical worsening. Sample size: 1 (case report) + 5 (case series). Dosage: 200 mg twice on day one, 100 mg daily on days 2 and 3. 

The results suggest that critically ill COVID-10 patients displaying features of macrophage activation-like syndrome might benefit from anakinra treatment. Sample size: 60 + 42 (tocilizumab instead). Dosage: 200 mg every 8 hours for 7 days. Main outcome: “…any 25% or more decrease in baseline Sequential Organ Failure Assessment (SOFA) score and/or at least 50% increase in the baseline PaO2/FiO2 ratio by day 8.”

In the study cohort, the treatment was generally safe and led to improved survival. Sample size: 17 + 28 control. Dosage: 400 mg IV for up to 14 days. 

Rapid and significant clinical improvement (including lower supplementary oxygen requirements) was observed. Sample size: 12 + 10 control. Dosage: 300 mg daily on days 1–5, dose tapered during days 6–8. 

Cumulative data from a case series of children suffering from COVID-19-related Multisystem inflammatory syndrome suggest a benefit of anakinra treatment, especially in children with high IL-1RA levels. Sample size: 5 patients received anakinra (alone or combined with other anti-inflammatory drugs). Dosage: 1.3 or 2 mg/kg. 

Treatment using anakinra and IVIg administered during two days led to clinical improvement in a COVID-19 patient with pancytopenia and high levels of inflammatory markers. Sample size: 1. Dosage: 100 mg a day. 

The therapy increased survival in both severely and critically ill patients. Sample size: 52 + 103 matched control. Dosage: 5 mg/kg IV twice a day. 

A protocol combining anakinra (ferritin level-dependent dosage) with other drugs (corticosteroids/IVIg/tocilizumab) based on ferritin levels and clinical status seemed to provide satisfactory clinical outcomes. Sample size: 311. Dosage: 2–4 mg/kg or 5–8 mg/kg daily for 10 days. 

Two juvenile patients with recent COVID-19 history were successfully treated for severe sinus bradycardia, which was refractory to the methylprednisolone and IVIg treatment. Sample size: 2. Dosage: 4 mg/kg daily for 10–14 days. 

A patient diagnosed with multisystem inflammatory syndrome related to COVID-19 was successfully treated using high-dose methylprednisolone, anakinra, acetylsalicylic acid, and IVIg. Sample size: 1. Dosage: 100 mg subcutaneously every 6 hours. 

A paediatric patient diagnosed with COVID-19-related multisystem inflammatory syndrome was successfully treated using methylprednisolone, anakinra, and IVIg. Sample size: 1. Dosage: 2–10 mg/kg, up to twice daily, based on clinical status. 

A paediatric patient with severe COVID-19, requiring extracorporeal membrane oxygenation, was successfully treated using methylprednisolone, anakinra, and remdesivir. Sample size: 1. Dosage: 100 mg every 6 hours on days 1–5, 100 mg every 12 hours on days 5–10, and 100 mg daily on days 11–13. 

Based on clinical observations, the authors conclude that anakinra treatment could be used in very severe COVID-19 cases when response to IVIg and corticosteroids is not satisfactory. Sample size: 23. Dosage: 5–10 mg/kg a day, up to 100 mg three times a day. 

Hospitalized kidney transplant patients who received anakinra or tocilizumab (AT) displayed better ordinal scale scores. Despite differences in rates of ICU admissions, secondary respiratory infections, or mortality were not significant compared to control, the authors suggest a possible benefit of AT therapy. Sample size: (14 + 4) pooled with tocilizumab + 15 control. Dosage: “...200 mg/12 h sc for 24 h and 200 mg/24 h with a maximum of 3 doses.” 

A paediatric patient on ECMO was treated with remdesivir, methylprednisolone, IVIg, and anakinra. Sample size: 1. 

IL-blockers (pooled data for anakinra and tocilizumab) increased the odds of extubation. Sample size: 24 (+ 26 pooled with Tocilizumab) out of 382 (the whole assessed cohort). 

The treatment significantly reduced mortality in the studied population. Sample size: 62 + 275 control (no IL inhibition). Dosage: 5 mg/kg twice a day until clinical benefit. Main outcome: Survival.

Based on observations of paediatric patients suffering from multisystem inflammatory syndrome, the authors state that anakinra and corticosteroids seem to be effective and safe. Sample size: 26.