Tocilizumab in the treatment of COVID-19—a meta-analysis

Abstract

Objective To evaluate whether IL-6 inhibitor tocilizumab (TCZ) reduces mortality among hospitalized COVID-19 patients. Methods Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TCZ versus placebo/control, for treatment of adults with COVID-19. Primary outcome was 28-30 days all-cause mortality. Search was conducted up to April 1st 2021. Two independent reviewers screened citations, extracted data, and assessed risk of bias. Relative risk (RR) with 95% confidence intervals (CI) were pooled. We performed subgroup analysis for patients with critical illness and sensitivity analyses. Results Eight RCTs were included, assessing 6,481 patients with mostly severe non-critical COVID-19 infection. TCZ was associated with a reduction in all-cause 28–30-day mortality compared to placebo/control (RR = 0.89, 95%CI 0.82-0.96). Among the subgroup of critically ill patients no reduced mortality was demonstrated (RR = 0.94, 95%CI 0.74-1.19). No mortality benefit with TCZ was demonstrated in trials that used steroids for >80% of patients. TCZ was associated with significantly reduced risk for mechanical ventilation (MV); for combined endpoint of death or MV; and for intensive care unit (ICU) admission. No significant difference in adverse events was demonstrated. Risk of serious superinfection was significantly lower with TCZ (RR = 0.57, 95%CI 0.35-0.93). Conclusion The treatment with TCZ reduces 28-30 days all-cause mortality, ICU admission, superinfections, MV and the combined endpoint of death or MV. Among critically ill patients, and when steroids were used for most patients, no mortality benefit was demonstrated. Additional research should further define sub-groups that would benefit most and preferred timing of administration of TCZ in severe COVID-19.

Clinical efficacy and safety of interleukin-6 receptor antagonists (tocilizumab and sarilumab) in patients with COVID-19: a systematic review and meta-analysis

“…Consistent with our findings, recent meta-analyses of randomized trials exploring the effect of tocilizumab treatment in patients with COVID-19 showed a favourable effect on mortality risk [ 31–35 ]. Some meta-analyses suggested that tocilizumab treatment had no significant positive effect on mortality, but these studies included non-randomized trials [ 36 , 37 ].…”

COVID-19 in Patients with Hematologic Malignancies: Outcomes and Options for Treatments

“…A prospective meta-analysis of randomized trials showed reduced 28-day all-cause mortality with the use of IL-6 antagonists in COVID-19 [ 83 ]. A meta-analysis demonstrated that tocilizumab is associated with reduced 30-day mortality, ICU admissions, mechanical ventilation, and superinfection rates in patients with COVID-19 not admitted to the ICU [ 84 ]. A randomized clinical trial of tocilizumab for the treatment of COVID-19 specifically in patients with cancer and COVID-19 (NCT04370834) was stopped prematurely after only enrolling 1 patient [ 81 ].…”

Tocilizumab Versus Baricitinib in Patients Hospitalized With COVID-19 Pneumonia and Hypoxemia: A Multicenter Retrospective Cohort Study

“…Anti-inflammatory treatment with dexamethasone was shown to reduce mortality in patients hospitalized with COVID-19 and requiring respiratory support (5). Subsequent trials have shown possible clinical benefit of the interleukin-6 (IL-6) inhibitors tocilizumab and sarilumab (6)(7)(8)(9)(10) and of the Janus kinase (JAK) inhibitors baricitinib and tofacitinib (11)(12)(13), both with and without concurrent steroid treatment (11)(12)(13)(14)(15)(16), although data are not dispositive. Despite this uncertainty, current guidelines for anti-inflammatory therapy recommend tocilizumab or baricitinib, and recommend sarilumab or tofacitinib as alternatives (17).…”