Hydroxychloroquine offers neither benefit nor harm for COVID-19 mortality
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Hydroxychloroquine was not associated with either benefit or harm regarding COVID-19 mortality, and the evidence supporting the effect of other antirheumatic therapies is inconclusive, noted data published in Arthritis & Rheumatology.
“There has been particular interest in the antimalarial agents hydroxychloroquine (HCQ) and chloroquine (CQ), which may inhibit SARS-CoV-2 replication by elevating endosomal pH or altering the glycosylation of the ACE2 receptor,” Michael Putman, MD, MSci, of Northwestern Medicine, and colleagues wrote. “After preliminary evidence also suggested a clinical benefit for HCQ, public acquisition resulted in shortages. More recently, a now-retracted study by Mehra et al. reported an association between HCQ use and increased mortality. Both concern for this potential risk and the aforementioned HCQ shortages have negatively impacted patients who take HCQ for rheumatic diseases.”
“Antirheumatic disease therapies may also mitigate the hyperinflammatory state caused by SARSCoV-2 infection, which has been associated with elevated levels of inflammatory cytokines,” they added. “Therapies that directly target the inflammatory cascade, including interleukin-6 (IL-6) inhibitors, interleukin 1 (IL-1) inhibitors, and glucocorticoids, have been widely adopted in clinical practice prior to the publication of ongoing randomized controlled trials. Similar considerations have led to speculation that tumor necrosis factor (TNF) inhibitors and the Janus kinase inhibitor baricitinib may be beneficial.”
To analyze the current evidence regarding antirheumatic and antimalarial drugs in treating COVID-19, Putman and colleagues conducted a systematic review and meta-analysis of published and pre-print databases. The literature search included articles in all languages published between Jan. 1, 2019, and April 1, 2020. Eligible studies reported on relevant clinical outcomes in five or more people who were infected with COVID-19 and were treated with antirheumatic therapy between Jan. 1, 2019, and May 29, 2020.
Later, pairs of reviewers screened articles, recorded data and assessed the risk for bias. In addition, the researchers, when possible, performed a meta-analysis of effect sizes using random-effects models. In all, the researchers identified 3,935 articles, of which 45 were included in the final analysis. These included 29 cohort studies, 12 case series and four randomized controlled trials. All included studies analyzed patients who were hospitalized, and 29 were published in a peer-reviewed journal.
According to the researchers, in a meta-analysis of three cohort studies with a low risk of bias, hydroxychloroquine was not significantly associated with mortality (pooled HR = 1.41; 95% CI, 0.832.42). Meanwhile, in a metaanalysis of two cohort studies with some concerns or a high risk of bias, anakinra (Kineret, SOBI) was associated with lower mortality (pooled HR = 0.2; 95% CI, 0.10.4). However, the researchers found that evidence for other antirheumatic drugs was inconclusive, and that the majority of other studies had a high risk for bias.
“First, hydroxychloroquine was not associated with benefit or harm in COVID-19,” Putman told Healio Rheumatology. “Second, the IL-1 inhibitor, anakinra, was associated with a reduced risk of death, but studies that evaluated this therapy had substantial risk of bias. Third, the observational data for other therapies was insufficient to make meaningful conclusions.”
“At the time of publication, the evidence for antirheumatic disease therapies in COVID-19 was not strong,” he added. “Since then, multiple large randomized controlled trials have released preliminary findings that confirmed our conclusions with regarding to hydroxychloroquine.”
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