Title: Efficacy of Antirheumatic Disease Therapies in Patients with COVID-19: A Systematic Review and Meta-analysis of the Current Evidence

Authors: Michael Putman MD, MSci,1 Yu Pei Eugenia Chock MD, MPH,2 Herman Tam MBBS, MSc et al on behalf of the Global Rheumatology Alliance

 

LAY SUMMARY

Preamble:

Several antirheumatic disease therapies have emerged as potential treatments for coronavirus 2019 disease (COVID-19) with particular interest in the antimalarial agents hydroxychloroquine (HCQ) and chloroquine (CQ). Widespread shortages of these medications have negatively impacted rheumatic patients. 

Antirheumatic disease therapies including steroids and antibodies that block different chemical pathways are thought to be beneficial though no large reviews of their effectiveness have been done. This study reviews and analyzes published and unpublished original scientific articles on different antirheumatic disease therapies for the treatment of COVID-19.

What was done?

A comprehensive online search in every language was done in March 2020 to identify relevant published and unpublished studies from 1st January to 1st April 2020. The search was repeated 2 months later to identify newer research. Studies on anti-rheumatic therapies that involved 5 or more patients with covid-19, produced original data and included important patient outcomes such as recovery or death among others were included in the final analysis.

Four patient researchers who had covid-19 themselves – 2 with autoimmune disease and 2 rheumatologists were involved in the study. Studies were grouped by risk of bias and level of reliability such that those with a high level of reliability and low risk of bias were prioritized. Each task was done by at least 2 people to enhance uniformity and a general vote was done where disagreements occurred.

What was found?

Of nearly 4,000 studies screened, 3,890 did not meet the strict conditions and were excluded. The final analysis included 45 studies, of which 6 could be analyzed together to estimate an overall effect. The studies included only hospitalized patients and most were conducted in China and France; roughly two-thirds published in a journal.

In the meta-analysis portion of the study, hydroxychloroquine was not associated with benefit or harm while chloroquine (with potentially more side effects) appeared to improve viral clearance though most studies had a high risk of bias. Anakinra – a biologic medication – appeared to lower the risk of death though there is need for caution as the studies evaluating anakinra had limitations. Studies of other antirheumatic disease therapies frequently had contradictory results, and many had a high risk of bias, precluding any firm conclusions regarding their potential efficacy.

What does it mean?

The findings from this study show that hydroxychloroquine is neither associated with benefit nor harm which is reassuring for patients taking them for rheumatic diseases. Additional studies, including clinical trials, are needed to inform the appropriate use of other  anti-rheumatic therapies for COVID-19. Some limitations exist with this study including the fact that it included only hospitalized patients and hence cannot apply to everyone as well as the fact that covid-19 research is growing at a very fast pace hence some studies may have been missed or recently published.