Systematic review and meta-analysis of anakinra, sarilumab, siltuximab and tocilizumab for COVID-19.
Thorax
; 76(9): 907-919, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-33579777
ABSTRACT
BACKGROUND:
There is accumulating evidence for an overly activated immune response in severe COVID-19, with several studies exploring the therapeutic role of immunomodulation. Through systematic review and meta-analysis, we assess the effectiveness of specific interleukin inhibitors for the treatment of COVID-19.METHODS:
Electronic databases were searched on 7 January 2021 to identify studies of immunomodulatory agents (anakinra, sarilumab, siltuximab and tocilizumab) for the treatment of COVID-19. The primary outcomes were severity on an Ordinal Scale measured at day 15 from intervention and days to hospital discharge. Key secondary endpoints included overall mortality.RESULTS:
71 studies totalling 22 058 patients were included, 6 were randomised trials. Most studies explored outcomes in patients who received tocilizumab (60/71). In prospective studies, tocilizumab was associated with improved unadjusted survival (risk ratio 0.83, 95% CI 0.72 to 0.96, I2=0.0%), but conclusive benefit was not demonstrated for other outcomes. In retrospective studies, tocilizumab was associated with less severe outcomes on an Ordinal Scale (generalised OR 1.34, 95% CI 1.10 to 1.64, I2=98%) and adjusted mortality risk (HR 0.52, 95% CI 0.41 to 0.66, I2=76.6%). The mean difference in duration of hospitalisation was 0.36 days (95% CI -0.07 to 0.80, I2=93.8%). There was substantial heterogeneity in retrospective studies, and estimates should be interpreted cautiously. Other immunomodulatory agents showed similar effects to tocilizumab, but insufficient data precluded meta-analysis by agent.CONCLUSION:
Tocilizumab was associated with a lower relative risk of mortality in prospective studies, but effects were inconclusive for other outcomes. Current evidence for the efficacy of anakinra, siltuximab or sarilumab in COVID-19 is insufficient, with further studies urgently needed for conclusive findings. PROSPERO REGISTRATION NUMBER CRD42020176375.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína Antagonista do Receptor de Interleucina 1
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Anticorpos Monoclonais Humanizados
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COVID-19
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Tratamento Farmacológico da COVID-19
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Anticorpos Monoclonais
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Thorax
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido