Treatment with interleukin-6 (IL-6) inhibitors decreased the risk of death among patients with COVID-19 infection by 75% compared with standard treatment, according to results of a systematic review and meta-analysis published in the European Journal of Internal Medicine.

Investigators conducted a systematic review of MEDLINE and Scopus databases from inception until October 2021. The review included only original randomized controlled trials (RCTs) that assessed the clinical characteristics and outcomes of adult patients with COVID-19 infection who received IL-6 inhibitors compared with those who received standard of care (SOC). The investigators extracted individual patient data and entered it into standardized, predesigned tables for evidence synthesis. The primary outcome was overall survival (OS), calculated using the Kaplan-Meier method. They used Cox proportional hazards regression to assess between-group differences.

There were 11 studies that met the inclusion criteria with a total of 7467 patients. A total of 983 (24%) deaths occurred among patients who received IL-6 inhibitors vs 3364 (29.6%) among those who received SOC.

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Pooled OS curves of individual patient data showed that patients who received IL-6 inhibitors had a significantly decreased risk of death compared with those who received SOC (hazard ratio [HR], 0.75; 95% CI, 0.69-0.82; P <.0001). This was confirmed in the sensitivity cumulative 2-stage meta-analysis that used the pooled HRs of the included RCTs.

Treatment with IL-6 inhibitors also was associated with a decreased risk for intubation and mechanical ventilation compared with SOC (P <.001), as well as an increased odds for hospital discharge (P <.001). A meta-regression analysis showed that OS among patients who received IL-6 inhibitors increased as the mean patient age increased, though it was not a statistically significant finding (P =.17).

This study was limited by the inability to assess patient-level prognostic covariates, and potential confounding due to the inability to account for differences in the peak incidence of COVID-19 between each country involved in the analysis.

The investigators noted the importance of recognizing IL-6 inhibitor-associated adverse effects, the most common of which is secondary infection.


Tasoudis PT, Arvaniti CK, Adamou AT, et al. Interleukin-6 inhibitors reduce mortality in coronavirus disease-2019: An individual patient data meta-analysis from randomized controlled trials. Eur J Intern Med. Published online April 6, 2022. doi:10.1016/j.ejim.2022.04.004 

This article originally appeared on Infectious Disease Advisor

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