Tocilizumab administration for severe COVID-19: Timing matters

Early administration (ie, pre-intubation/noninvasive ventilation) of the interleukin-6 receptor blocker tocilizumab in patients with severe COVID-19 led to more favourable outcomes compared with late administration (ie, post-intubation/noninvasive ventilation), according to data presented at ATS 2021.

“[We hypothesized] that tocilizumab given during or after the need for mechanical ventilation will not improve outcomes, since the effects of the cytokine storm [brought about by the release of pro-inflammatory cytokines] in the pulmonary alveolar epithelium is irreversible,” noted Dr Sofia Salome Aparece-Solis from the Chong Hua Hospital, Fuente Osmeña, Cebu City, Philippines, in her poster presentation.

“Early administration of tocilizumab may ameliorate the hyperinflammatory response, which may prevent intubation. [Conversely,] administration of tocilizumab after the cytokine storm – when respiratory failure has ensued – may be detrimental [in this patient setting],” she added.

Aparece-Solis and her team retrospectively evaluated 90 patients (mean age 64 years, 58 percent male; n=84 and 6 intubated and non-intubated, respectively) who were admitted to the intensive care unit for severe to critical COVID-19. Of these, 68 received tocilizumab (n=65 and 3 in the intubated and non-intubated arms, respectively). [ATS 2021, abstract A3840]

Of the intubated patients who received tocilizumab, 26 received the drug early (mean 3.96 days pre-intubation), while 39 had it late (mean 0.76 days post-intubation).

Compared with those who received tocilizumab late, 28-day mortality rate was significantly lower among those who were given the drug early (30.77 percent vs 56.41 percent; hazard ratio [HR], 0.40; p=0.042). This remained significant after adjusting for age and sex (HR, 0.37; p=0.013).

Regarding time to death, early vs late administration of tocilizumab also appeared to deliver a similar protective benefit, yielding an HR of 0.43.

Survival-wise however, timing did not seem to make any difference, as reflected by the similar survival rates between the early and the late administration arms (mean, 17.42 vs 18.62 days; p=0.67). Conversely, the difference was significant when using in-hospital days as time variable (mean, 61.25 vs 38.25 days; p=0.026).

Taken together, the findings suggest that early administration of tocilizumab may confer a protective benefit for patients with severe COVID-19. These also add to the growing literature supporting the benefit of tocilizumab in this setting. “[Tocilizumab appears to] successfully control an impending cytokine storm in severe COVID-19 patients,” said Aparece-Solis.

Another study from Ecuador similarly looked into the effect of the timing of tocilizumab administration in patients with severe COVID-19. The study comprised 56 patients (mean age 61.7 years, 70 percent male) who received corticosteroids and tocilizumab. Of these, 43 survived, with a mean time to hospital discharge of 11.5 days. [ATS 2021, abstract A2653]

The negative correlation observed between days prior to tocilizumab administration and survival status was statistically significant (rpb=–0.290; p=0.03).

“[This suggests that] early administration of tocilizumab was associated with a greater likelihood of survival, an observation that could not be reproduced with steroids,” said Dr Ivan Cherrez-Ojeda from Respiralab, Guayaquil, Ecuador.

Larger-scale trials are warranted to ascertain the benefits of tocilizumab and its timing of administration for patients with severe COVID-19.