Does timing matter on tocilizumab administration? Clinical, analytical and radiological outcomes in COVID-19

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 SaO 2 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 (90day 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.

Effect of Tocilizumab in Mortality among Patients with Severe and Critical Covid-19: Experience in a Third-Level Medical Center

“…Since 30% received the drug more than 24 h after IMV onset, it is likely that late treatment had an impact on the outcome, although the optimal timing is yet to be proven 33 . A recently published observational study reported a lower 90-day mortality in patients that received tocilizumab within the first 10 days after symptom onset when compared with those that received the drug after day 11 34 . In our study, the prolonged time from admission to tocilizumab administration was due to low availability and high cost of the drug in our setting.…”

Hyperhemolysis in a patient with sickle cell disease and recent SARS‐CoV‐2 infection, with complex auto‐ and alloantibody work‐up, successfully treated with tocilizumab

“…A meta‐analysis of six randomized controlled trials of COVID‐19 patients showed that tocilizumab was associated with a statistically significant reduction in the primary composite outcome of mechanical ventilation or 28‐day mortality 27 . The time‐course for achieving measurable improvement after tocilizumab in COVID‐19 has been reported as 5–6 days 28,29 …”

“… 27 The time‐course for achieving measurable improvement after tocilizumab in COVID‐19 has been reported as 5–6 days. 28 , 29 …”

Barotrauma, invasive ventilation, and timing of tocilizumab as predictors of mortality along with inflammatory markers and comorbidities in critically ill COVID-19 patients: A retrospective study

“…Moreno Diaz et al . [ 15 ] reported that the use of tocilizumab within 10 days of symptom onset is reported to significantly reduce the mortality at day 90 in severe COVID-19 cases. Although insignificant, we observed that in survivors, tocilizumab administration was a day earlier than in non-survivors.…”