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PLoS One
. 2023 Dec 29;18(12):e0295838.
doi: 10.1371/journal.pone.0295838. eCollection 2023. Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial
Jonas Sundén-Cullberg 1 2 , Puran Chen 3 , Henrike Häbel 4 , Paul Skorup 5 , Helena Janols 5 , Johan Rasmuson 6 , Katarina Niward 7 , Åse Östholm Balkhed 7 , Katerina Chatzidionysiou 8 , Hilmir Asgeirsson 1 2 , Ola Blennow 1 2 , Åsa Parke 1 2 , Anna-Karin Svensson 1 2 , Jagadeeswara Rao Muvva 3 , Hans-Gustav Ljunggren 3 ; Karolinska KI/K COVID-19 Treatment Working Group; Anna-Carin Horne 9 , Ulrika Ådén 10 , Jan-Inge Henter 11 , Anders Sönnerborg 1 12 , Jan Vesterbacka 1 2 , Piotr Nowak 1 2 , Jon Lampa 8
Affiliations
Background: Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration.
Methods: The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 μg/L and at least two points where one point was awarded for lymphocytes < 1x 109/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery.
Results: Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly.
Conclusion: Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020-00174824).
. 2023 Dec 29;18(12):e0295838.
doi: 10.1371/journal.pone.0295838. eCollection 2023. Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial
Jonas Sundén-Cullberg 1 2 , Puran Chen 3 , Henrike Häbel 4 , Paul Skorup 5 , Helena Janols 5 , Johan Rasmuson 6 , Katarina Niward 7 , Åse Östholm Balkhed 7 , Katerina Chatzidionysiou 8 , Hilmir Asgeirsson 1 2 , Ola Blennow 1 2 , Åsa Parke 1 2 , Anna-Karin Svensson 1 2 , Jagadeeswara Rao Muvva 3 , Hans-Gustav Ljunggren 3 ; Karolinska KI/K COVID-19 Treatment Working Group; Anna-Carin Horne 9 , Ulrika Ådén 10 , Jan-Inge Henter 11 , Anders Sönnerborg 1 12 , Jan Vesterbacka 1 2 , Piotr Nowak 1 2 , Jon Lampa 8
Affiliations
- PMID: 38157348
- PMCID: PMC10756513
- DOI: 10.1371/journal.pone.0295838
Background: Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration.
Methods: The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 μg/L and at least two points where one point was awarded for lymphocytes < 1x 109/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery.
Results: Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly.
Conclusion: Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020-00174824).