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Does timing matter on tocilizumab administration? Clinical, analytical and radiological outcomes in COVID-19
  1. Raquel Moreno Diaz1,
  2. Miguel Angel Amor García1,
  3. Francisco Javier Teigell Muñoz2,
  4. Leonardo Ernesto Saldaña Perez3,
  5. María Mateos Gonzalez2,
  6. Jose Antonio Melero Bermejo2,
  7. Alberto López Hernández1,
  8. Laura Reyes Marquez4,
  9. Maria Teresa De Guzman García-Monge2,
  10. Jose Luis Perez Quero2,
  11. Marcela Patricia Homez Guzman5
  1. 1 Pharmacy, Hospital Universitario Infanta Cristina, Parla, Spain
  2. 2 Internal Medicine, Infanta Cristina University Hospital, Parla, Spain
  3. 3 Neumology, Getafe University Hospital, Getafe, Madrid, Spain
  4. 4 Radiologist, Hospital Universitario Infanta Cristina, Parla, Madrid, Spain
  5. 5 Critical Care, Hospital Universitario Infanta Cristina, Parla, Madrid, Spain
  1. Correspondence to Raquel Moreno Diaz, Pharmacy, Hospital Universitario Infanta Cristina, 28981 Parla, Spain; rmorenod{at}salud.madrid.org

Abstract

Introduction While there are no pharmacological treatments with proven efficacy for coronavirus disease 2019 (COVID-19), tocilizumab has emerged as a candidate therapy. Some aspects of this therapy are still unknown, including the optimal timing of administration.

Objective This observational study aimed to compare the 90-day mortality in two cohorts of patients when the drug was administered within the first 10 days from onset of symptoms or after day 11.

Methods Patients hospitalised with severe COVID-19 pneumonia who had received tocilizumab were divided into two groups according to when the medication was administered. The primary outcome was 90-day mortality. Secondary outcomes were 30-day mortality, clinical improvement on a 6-item scale by day 6, biomarker improvement by day 6, radiological image improvement by day 10 and SaO2 quotient by day 6. The results in the two groups were compared. Additionally, adverse events relating to tocilizumab were recorded.

Results A total of 112 patients were analysed. Both groups were epidemiologically comparable. The results obtained in the primary efficacy variable of the study (90-day mortality) showed a statistically significant difference in the subgroups according to the time of administration of tocilizumab (18.6% vs 5.0%, p=0.048). There was clinical improvement in 24.1% of patients at 6 days, with similar behaviour in both subgroups. No statistically significant differences were found in the percentage of patients who achieved radiological improvement at 10 days or in the other inflammatory parameters, with the exception of significant reductions in lactate dehydrogenase and C-reactive protein. Administration of tocilizumab was not associated with relevant adverse events.

Conclusion To our knowledge, this is the first report of data regarding the timing of administration of tocilizumab in patients with COVID-19 pneumonia. A strategy involving tocilizumab administration after 10 days from onset of symptoms may decrease mortality. Further randomised controlled trials are needed to confirm this emerging hypothesis.

  • COVID-19
  • critical care
  • pulmonary medicine
  • radiology
  • complementary therapies

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

This article is made freely available for personal use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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