Systematic review and meta-analysis of interleulin-6 inhibitors in reducing mortality for hospitalized patients with...

One year after the declaration of the SARS-CoV-2 pandemic, only  dexamethasone has clearly shown a reduction in mortality for COVID-19  hospitalized patients. For interleukin-6 inhibitors, results are variable and  nclear. The objective was to review and analyze the effect of tocilizumab and  sarilumab on survival in this setting.

The PRISMA statements were fulfilled for the systematic review. A  systematic search in Medline, Embase and medRxiv was conducted to identify  randomized controlled trials with tocilizumab or sarilumab in hospitalized  patients with COVID-19. Mortality data from non-critical and critical patients  were extracted. A random-effects (DerSimonian-Laird) meta-analysis was  performed for both subgroups and the whole population using MAVIS software  v. 1.1.3. Similarity and homogeneity among trials were assessed.

Twenty-five and 23 articles were identified in Medline and Embase,  respectively, five were trials with tocilizumab and/or sarilumab; two more were  identified at medRxiv. Seven randomized clinical trials fulfilled the  inclusion criteria. Another trial was pre-published and included post-hoc. The  meta-analysis, with eight randomized clinical trials and 6,340 patients, showed  a benefit on mortality for interleukin-6  heterogeneity (I2 = 7%), but  a low similarity among studies. The results showed no differences among  critical and non-critical patients. A sensitivity analysis excluding non-similar or  heterogeneous studies showed different results, without benefit and with low  precision of the result in non-critical patients.

A benefit in mortality for interleukine-6 inhibitors was found, but  with important differences among the scenarios analyzed in the clinical  trials. Positive results are mainly caused by two randomized clinical trials which  are similar in concomitant use of steroids and veryhigh mortality in  critical patents. Sarilumab was poorly represented in the meta-analysis.  Nevertheless, an association between the benefit and the critical/non-critical  condition was not found. More randomized clinical trials, mainly focused in  atients at high mortality risk, are needed to confirm the benefit of interleukine- 6 inhibitors for COVID-19. Sarilumab was underrepresented in the meta- analysis.