Patients treated with tocilizumab for COVID-19 had more than 11 times the risk of developing neutropenia compared with those who received placebo, according to a recent review.
In a rapid systematic review, researchers evaluated the association between serious adverse events (SAEs) and FDA–authorized COVID-19 treatments. The review, which was commissioned by the Agency for Healthcare Research and Quality and conducted to inform the Health Resources and Services Administration’s Countermeasures Injury Compensation Program, aimed to assess whether convalescent plasma, antiviral agents, or monoclonal antibodies were linked to SAEs in treated patients.
According to the results published in Open Forum Infectious Diseases, no antiviral treatments—remdesivir, nirmatrelvir–ritonavir, or molnupiravir—were associated with an increased risk of any SAE. Similarly, monoclonal antibodies that target the SARS-CoV-2 spike protein—including bamlanivimab–etesevimab, bebtelovimab, sotrovimab, casirivimab–imdevimab, and tixagevimab–cilgavimab—were not associated with elevated SAE risk.
In contrast, tocilizumab, an interleukin 6 receptor antagonist, was associated with neutropenia in one randomized trial that was rated at low risk of bias. In that study, neutropenia occurred in 22 of 161 patients who were treated with tocilizumab compared with 1 of 82 in the placebo group.
A separate trial reported neutropenia in 4 of 295 tocilizumab-treated patients and none in 143 controls, though this result was not statistically significant. Certainty of evidence for this association was rated moderate. Infection risk was also elevated in one trial (RR = 1.72), but findings across other studies were inconsistent. The strength of the evidence supporting this association was considered low.
Among 15 studies of convalescent plasma, one trial involving patients with hematologic cancers showed a higher risk of serious bleeding (RR = 1.96) and infection (RR = 1.79). Findings from other studies were mixed and did not show a consistent pattern. Evidence that supported associations with thrombotic events and other complications was considered limited.
Margaret A Maglione of the Southern California Evidence Review Center at the University of Southern California Keck School of Medicine in Los Angeles, California, and colleagues searched PubMed, ClinicalTrials.gov, and FDA submission databases from January 2020 through December 2023 and included only controlled studies with at least one U.S. site.
Of 320 full-text articles reviewed, 54 studies met eligibility criteria, including 31 randomized controlled trials and 23 controlled observational studies. Serious adverse event data were abstracted at grade 3 or higher using standardized definitions; and risk ratios were calculated for intervention versus placebo, no treatment, or usual care.
Most FDA-authorized COVID-19 treatments were not associated with an increased risk of SAEs. However, specific subgroups—particularly hospitalized or immunocompromised patients—may face elevated risks with tocilizumab or convalescent plasma. The researchers noted the importance of continued post-market safety surveillance.
"These consequences may be confused with toxicities of the interventions. Based on our analysis, approved treatments for COVID-19 should be prescribed as clinically indicated, although continued vigilance is warranted to identify rare and potentially significant toxicities that may arise in clinical practice," the researchers concluded.
No conflicts of interest were reported.
