Immunomodulatory therapies for severe COVID-19: literature update

Efficacy and safety of immunomodulatory therapies used for the management of SARS-CoV-2 infection were analysed and summarised by means of a systematic literature review covering 401 papers, with the aim of informing the EULAR taskforce on COVID-19 immunomodulatory therapies and pathophysiology from a rheumatology perspective.

Adults with a proven SARS-CoV-2 infection, symptomatic or asymptomatic COVID-19, and without rheumatic disease prior to infection were included. Dr Alessia Alunno (University of Perugia, Italy) presented the results [1]. Glucocorticoid therapy in addition to standard of care (5 randomised clinical trials [RCTs]) showed a reduced mortality rate compared with standard treatment for oxygen-receiving (RR 0.89; 95% CI 0.79–1.00) and mechanically ventilated (RR 0.71; 95% CI 0.58–0.86) COVID-19 patients in the large RCT RECOVERY (NCT04381936; n=6,425). In contrast, the use of glucocorticoids in patients not receiving supplemental oxygen increased the mortality rate (RR 1.27; 95% CI 1.00–1.61). Older age of COVID-19 patients (>60 years) was associated with reduced mortality when they were treated with glucocorticoids (RR 0.75; 95% CI 0.56–1.01).

Five RCTs on tocilizumab did not demonstrate mortality benefits in COVID-19 patients. However, the largest included trial, REMAP-CAP (NCT02735707), did show a reduced mortality of additional tocilizumab treatment next to standard of care (RR 0.78; 95% CI 0.63–0.97). In addition, this trial showed that tocilizumab users had a lower risk of disease progression towards mechanical ventilation or death (RR 0.78, 95% CI 0.65–0.94). Clinical worsening or time to improvement were not influenced by tocilizumab administration.

Hydroxychloroquine did not provide mortality benefits for COVID-19 patients (5 RCTs). In fact, 1 RCT on hydroxychloroquine showed that administering this drug could increase mortality rate in this population (RR 1.18; 95% CI 0.90–1.56).

One anakinra RCT was included in the systematic review. No benefits were observed for this drug. The effect of baricitinib (1 RCT) on mortality rate in COVID-19 patients was not significant (RR 0.85; 95% CI 0.40–1.07). Dr Alunno added that, in oxygen-receiving patients, baricitinib plus remdesivir significantly improved mortality rate and shortened the time to recovery. Moreover, the rate of adverse events was not increased by the additional administration of baricitinib.

Dr Alunno concluded that robust evidence on the efficacy of immunomodulatory drugs for the treatment of SARS-CoV-2 infections is limited. The number of investigated outcomes is low and only a few drugs have been studied adequately.

Editor’s note: Since the congress further data has emerged supporting the use of tocilizumab in severe COVID-19 as summarised in a recent meta-analysis [2].

1. Alunno A, et al. Immunomodulatory therapies for severe forms of COVID-19: a systematic literature review to inform EULAR points to consider. OP0287, EULAR 2021 Virtual Congress, 2–5 June.
2. The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. JAMA 2021. DOI: 10.1001/jama.2021.11330.

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Posted on 2 August 20213 August 2021