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

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 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.