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0 0.5 1 1.5 2+ Mortality 1% Improvement Relative Risk HCQ for COVID-19  Ip et al.  LATE TREATMENT Is late treatment with HCQ beneficial for COVID-19? Retrospective 2,512 patients in the USA No significant difference in mortality Ip et al., PLoS ONE, May 2020 Favors HCQ Favors control

Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study

May 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments.
Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HCQ during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), HCQ alone (HR, 1.02 [95% CI, 0.83-1.27]), or HCQ+AZ (HR, 0.98 [95% CI, 0.75-1.28]). Misclassification is possible due to manual abstraction of EHR data. They observed a change in the prescribing patterns of HCQ during the study timeframe. Confounding by indication.
risk of death, 1.0% lower, HR 0.99, p = 0.93, treatment 432 of 1,914 (22.6%), control 115 of 598 (19.2%), adjusted per study.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Ip et al., 25 May 2020, retrospective, database analysis, USA, peer-reviewed, 32 authors, average treatment delay 5.0 days.
This PaperHCQAll
Hydroxychloroquine and tocilizumab therapy in COVID-19 patients—An observational study
Andrew Ip, Donald A Berry, Eric Hansen, Andre H Goy, Andrew L Pecora, Brittany A Sinclaire, Urszula Bednarz, Michael Marafelias, Scott M Berry, Nicholas S Berry, Shivam Mathura, Ihor S Sawczuk, Noa Biran, Ronaldo C Go, Steven Sperber, Julia A Piwoz, Bindu Balani, Cristina Cicogna, Rani Sebti, Jerry Zuckerman, Keith M Rose, Lisa Tank, Laurie G Jacobs, Jason Korcak, Sarah L Timmapuri, Joseph P Underwood, Gregory Sugalski, Carol Barsky, Daniel W Varga, Arif Asif, Joseph C Landolfi, Stuart L Goldberg
PLOS ONE, doi:10.1371/journal.pone.0237693
Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings
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Late treatment
is less effective
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