Treatment with tocilizumab within 10 days of symptom onset was found to be associated with a decreased mortality risk in patients hospitalized with severe SARS-CoV-2 infection when , especially among those treated with concomitant corticosteroids, according to results of a systemic review and meta-analysis published in Pharmacotherapy.

In this meta-analysis, researchers analyzed data from 57 studies that enrolled a total of 20,616 patients who were hospitalized with COVID-19 between January 2020 and April 2021. Of the 57 studies analyzed, 47 were controlled observational studies (44 retrospective and 3 prospective) and 10 were randomized clinical trials. Patients included in these studies received treatment with either tocilizumab plus standard care (n=7668) or standard care alone (n=12,948).

Among patients in both treatment groups, 1915 and 4410 who received tocilizumab plus standard care or standard care alone were admitted to an intensive care unit (ICU) with reported mortality, respectively. Of note, there were more patients treated with concomitant corticosteroids in the tocilizumab group vs those in the standard care alone group (55.8% vs 41.1%, respectively; P <.001).


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Although significant heterogeneity was found among the included studies (I2=82%; P <.001), the pooled odds ratio (OR) of hospital-wide mortality among patients in the tocilizumab group, including those who were admitted to an ICU, was 0.73 (95% CI, 0.56-0.93). In patients who received tocilizumab plus concomitant corticosteroids, the pooled OR of hospital-wide mortality, including among those admitted to an ICU, was 0.67 (95% CI, 0.54-0.84).

On further analysis, the researchers found that the pooled OR of hospital-wide mortality was decreased among patients who were administered tocilizumab early (≤10 days from symptom onset) vs those who were administered tocilizumab late (>10 days from symptom onset): 0.71 (95% CI, 0.35-1.42) vs 0.83 (95% CI, 0.48-1.45).

Among patients treated with tocilizumab, those who received the medication in an ICU were found to have a decreased risk of mortality (OR, 0.66; 95% CI, 0.59-0.76) vs those who received the medication in conventional wards (OR, 1.25; 95% CI, 0.74-2.18). The researchers noted that the greater benefit of tocilizumab treatment observed among patients admitted to an ICU, especially when administered early, may be due those patients having increased inflammation compared with those treated in a conventional ward.

Limitations of this study included the inability to assess the effect of corticosteroids from that of tocilizumab, as well as the efficacy and safety of tocilizumab among those with different levels of COVID-19 disease severity. Further, the effect of COVID-19 vaccines and current care practices were not reflected in the included studies as they were conducted during the initial phases of the pandemic.

According to the researchers, treatment with tocilizumab and concomitant corticosteroids is indicated for “patients [hospitalized] with [severe COVID-19 complicated by] lung injury and systemic hyperinflammatory syndrome. In addition, “respiratory status or admission to the ICU [are] still only surrogates for [COVID-19] disease severity or inflammation status of patients with [SARS-CoV-2 infection],” the researchers concluded.

Disclosure: One author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.

Reference

Rubio-Rivas M, Forero CG, Mora-Luján JM, et al. Beneficial and harmful outcomes of tocilizumab in severe COVID-19: a systematic review and meta-analysis. Pharmacotherapy. Published online September 24, 2021. doi:10.1002/phar.2627