
Arthritis drugs have taken the spotlight in many COVID-19 trials. Two of the latest studies to come out assessed the efficacy of tocilizumab and found that it may reduce mortality rate in COVID-19 patients, although not without adverse events.
One study, published in Clinical Infectious Diseases, wrote, “Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is approved treatment.”
This single-center cohort study included 154 COVID-19 patients requiring mechanical ventilation. The main outcome measure was survival probability postintubation when comparing patients treated with tocilizumab (n=78) versus non-tocilizumab-treated patients (controls; n=76).
Patients were followed for a median (range) 47 (28-67) days. For the most part, baseline characteristics were similar between the tocilizumab and control groups, except mean age (55 vs. 60 years), likelihood of having chronic pulmonary disease (10% vs. 28%), and D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). When looking at inverse probability weighting-adjusted models, tocilizumab patients had a 45% lower mortality risk (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.33 to 0.90) as well as improved ordinal outcome scale status (odds ratio per 1-level increase, 0.58; 95% CI, 0.36 to 0.94). The rate of superinfections was significantly higher among tocilizumab patients than controls (54% vs. 26%; P<0.001), but the 28-day case fatality rate did not largely differ between tocilizumab patients with versus without superinfection (22% vs. 15%; P=0.42).
Tocilizumab Should Be Used ‘Cautiously’
The second study was published in the Journal of Infection.
“Interleukin-6 (IL-6) is a cytokine involved in the physiological inflammatory reaction and immune response but it has also been recognized also as a major driver in severe diseases such as chimeric antigen receptor T-cell (CAR-T)-associated cytokine release syndrome (CRS)5 and KSHV-associated inflammatory cytokine syndrome (KICS),” the authors said here. “Moreover, plasma IL-6 levels are elevated in ICU patients with COVID-19 and they appear to be positively correlated with mortality. As a consequence of these evidences, tocilizumab (TCZ), a recombinant humanized monoclonal antibody acting as IL-6 receptor agonist, has been proposed for the treatment of patients affected by COVID-19.”
In this study, patients consecutively admitted to a single center with severe or critical COVID-19 between March 13 and April 3 were retrospectively reviewed. Patients treated with tocilizumab (n=74) were matched 1:2 to non-tocilizumab-treated controls (n=148) based on age, sex, disease severity, P/F, Charlson Comorbidity Index, and time from onset of symptoms to hospital admittance.
Most of the patients were male (81.5%) and Caucasian (82%); the median age was 59 years. Most patients (69.8%) had critical-stage disease. Patients treated with tocilizumab, compared to controls, had better overall survival (HR, 0.499; 95% CI, 0.262 to 0.952; P=0.035) but had a longer hospital length of stay (HR, 1.658; 95% CI, 1.088 to 2.524; P=0.019), largely attributed to biochemical respiratory and infectious adverse events.
The researchers concluded here, “This study confirms the potentially effectiveness of [tocilizumab] on COVID-19 — especially in critically ill patients — with a reliable comparison group that allows to weigh the potential clinical impact of this treatment. Nevertheless, we suggest using it cautiously due to drug-related adverse events, remarkably transitory respiratory worsening and bacterial infections.”