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Antirheumatic Disease Therapies for the Treatment of COVID-19: A Systematic Review and Meta-Analysis
Michael Putman1, Yu Pei Eugenia Chock2, Herman Tam3
1Northwestern Medicine, Chicago, Illinois, United States.
Insights
This systematic review found hydroxychloroquine did not impact COVID-19 mortality. Evidence for other antirheumatic therapies in treating coronavirus disease 2019 (COVID-19) remains inconclusive.
Area of Science:
- Rheumatology
- Infectious Diseases
- Clinical Pharmacology
Background:
- Antirheumatic disease therapies have been explored for treating coronavirus disease 2019 (COVID-19).
- Evidence regarding their efficacy and safety in COVID-19 patients is limited.
- A comprehensive review of current data is necessary.
Purpose of the Study:
- To systematically review and meta-analyze existing evidence on the use of antirheumatic disease therapies for COVID-19.
- To assess the impact of these therapies on relevant clinical outcomes, particularly mortality.
- To identify gaps in the current research.
Main Methods:
- A systematic search of published and preprint databases was conducted.
- Studies involving at least five patients treated with antirheumatic therapies for COVID-19 between January 2019 and May 2020 were included.
- Data extraction, risk of bias assessment, and random-effects meta-analysis were performed.
Main Results:
- Out of 3,935 identified articles, 45 studies (including RCTs, cohort studies, and case series) met the inclusion criteria.
- Hydroxychloroquine use showed no significant association with mortality in a meta-analysis of low-bias cohort studies (HR 1.41; 95% CI 0.83, 2.42).
- Anakinra use was associated with lower mortality in a meta-analysis of higher-bias cohort studies (HR 0.25; 95% CI 0.12, 0.52).
- Evidence for other antirheumatic therapies was inconclusive, with most studies having a high risk of bias.
Conclusions:
- Hydroxychloroquine treatment was not associated with significant benefit or harm concerning COVID-19 mortality.
- Current evidence on the effectiveness of other antirheumatic disease therapies for COVID-19 is inconclusive.
- Further high-quality research is needed to clarify the role of these therapies in managing COVID-19.
Objective:
Antirheumatic disease therapies have been used to treat coronavirus disease 2019 (COVID-19) and its complications. We conducted a systematic review and meta-analysis to describe the current evidence.
Methods:
A search of published and preprint databases in all languages was performed. Included studies described ≥1 relevant clinical outcome for ≥5 patients who were infected with severe acute respiratory syndrome coronavirus 2 and were treated with antirheumatic disease therapy between January 1, 2019 and May 29, 2020. Pairs of reviewers screened articles, extracted data, and assessed risk of bias. A meta-analysis of effect sizes using random-effects models was performed when possible.
Results:
The search identified 3,935 articles, of which 45 were included (4 randomized controlled trials, 29 cohort studies, and 12 case series). All studies evaluated hospitalized patients, and 29 of the 45 studies had been published in a peer-reviewed journal. In a meta-analysis of 3 cohort studies with a low risk of bias, hydroxychloroquine use was not significantly associated with mortality (pooled hazard ratio [HR] 1.41 [95% confidence interval (95% CI) 0.83, 2.42]). In a meta-analysis of 2 cohort studies with some concerns/higher risk of bias, anakinra use was associated with lower mortality (pooled HR 0.25 [95% CI 0.12, 0.52]). Evidence was inconclusive with regard to other antirheumatic disease therapies, and the majority of other studies had a high risk of bias.
Conclusion:
In this systematic review and meta-analysis, hydroxychloroquine use was not associated with benefit or harm regarding COVID-19 mortality. The evidence supporting the effect of other antirheumatic disease therapies in COVID-19 is currently inconclusive.
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