Re: Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial
Is tocilizumab invalid? Or used at a wrong timing in COVID-19 patients
Viviane C Veiga et al. reported that COVID-19 patients could not benefit from tocilizumab therapy. Instead, the application of tocilizumab might increase mortality . Thus, the trial was stopped early. Although the study showed potential risks of tocilizumab, these results should not prevent its application to other COVID-19 patients. John H. Stone et al. reported that tocilizumab did not prevent intubation or death in moderately COVID-19 patients. But in terms of safety, the incidence of serious infections in the tocilizumab group was lower (13[8.1%] vs. 14[17.1%]; P=0.03) . Multiple clinical trials had verified the safety of tocilizumab [2,3,4]. Moreover, due to the wide confidence intervals of this study, some benefit (or harm) from tocilizumab might exist .
In the study of Carlos Salama et al. , the incidence of mechanical ventilation or death by 28 days in patients received tocilizumab (12.0%; 95% confidence interval [CI], 8.5 to 16.9) was significantly lower than in placebo group (19.3%; 95% CI, 13.3 to 27.4) (hazard ratio, 0.56; 95% CI, 0.33 to 0.97; P=0.04). Shruti Gupta et al. performed early tocilizumab administration (within 2 days of ICU admission) in 3924 critical COVID-19 patients . The results showed the death rate of patients treated with tocilizumab significantly decreased.
John H. Stone considered that interleukin-6 and other inflammatory proteins increasing reflect the host's response to infection, rather than a leading part of inflammation amplifying . However, another possibility is that the application of tocilizumab is too late to prevent the serious inflammation induced by Il-6. Actually, in almost all randomized trials, the tocilizumab is used after the symptoms last for many days [1-3]. This may also be the reason why the patients in Shruti Gupta’s study benefit from tocilizumab.
Therefore, tocilizumab should not be sentenced to be invalid. The clinical trial design and patient standards should be improved to explore the patient population that would benefit from tocilizumab.
1. Veiga VC, Prats J, Farias DLC, et al. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. Bmj 2021;372:n84.
2. Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med. 2020;383(24):2333-2344.
3. Salama C, Han J, Yau L, et al. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021;384(1):20-30.
4. Gupta S, Wang W, Hayek SS, et al. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Intern Med. 2021;181(1):41-51.
Competing interests: No competing interests