No mortality benefit found for hydroxychloroquine or tocilizumab for the treatment of COVID-19

1. Hydroxychloroquine use in hospitalized and tocilizumab use in ICU lab-positive COVID-19 patients were not been associated with decreased death.

Evidence Rating Level: 2 (Good)

There is ongoing research into evaluating potential treatment options for COVID-19. Despite conflicting evidence, hydroxychloroquine (with or without azithromycin) remains a popular option, while  preliminary results from CORIMUNO-TOCI trial show potential for tocilizumab, an IL-6 inhibitor, as an emerging treatment option. Hydroxychloroquine’s mechanism of action is thought to involve preventing viral entry by affecting angiotensin converting enzyme 2 and raising the pH of endosomes (via studies done on the original SARS-CoV virus) and by decreasing pro inflammatory cytokines and inhibiting signalling pathways by accumulating in lymphocytes and macrophages, while tocilizumab mediated IL-6 blockade is thought to prevent its effect of the interleukin on cytokine storms. Recent observational cohort studies of 1376 and 1438 patients show no association between hydroxychloroquine and intubation or death (HR 1.04, HR 1.35), even with azithromycin (HR 1.08). In this retrospective, observational, multicenter cohort study, 2512 hospitalized SARS-CoV 2 PCR-positive patients had received either hydroxychloroquine, hydroxychloroquine and azithromycin, azithromycin or neither therapy and the association with associated death was examined. Patients hospitalized between March 1 2020 to April 22, 2020 were chosen and followed-up with until May 5, 2020. Propensity-score adjusted analysis did not show decrease mortality with hydroxychloroquine (aHR 1.02, 95% 0.82-1.27), hydroxychloroquine and azithromycin (aHR 0.98, 95% CI 0.75-1.28), azithromycin (aHR 0.89, 95% CI 0.72-1.10). An additional component of this study is the evaluation of 547 SARS-CoV2 PCR-positive patients in the ICU and the association of tocilizumab exposure during their ICU stay (n=134) with associated mortality. Propensity-score adjusted analysis did not show a significant difference in mortality compared to no exposure however a trend was noted (aHR 0.76, 95% CI 0.57-1.00). Study findings are in keeping with recent literature that have found questionable benefits for the use of hydroxychloroquine for treatment of COVID-19. Likewise, no mortality benefit was found for the use of tocilizumab, though further larger scaled randomized studies may provide further insight into the trends observed in the present trial.

Click to read the study in PlosONE

Image: PD

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