Monoclonal antibodies for COVID-19 treatment up risks of hepatotoxicity, neutropenia

Treatment with monoclonal antibodies (mAbs) among COVID-19 patients is associated with a higher risk of hepatotoxicity and neutropenia when compared with standard of care (SoC) or placebo, reports a study.

Moreover, the chance of infusion reactions is also increased with the use of such medications among this population.

“The disease-related serious adverse events were likely to reduce with the use of mAbs as compared to SoC/placebo, suggesting a possible reduction in disease progression by mAbs,” the researchers said.

This systematic review and meta-analysis accessed databases from January 2020 to September 2023. Randomized clinical trials (RCTs) assessing mAbs for the treatment of COVID-19 regardless of disease severity were identified.

Two independent reviewers carried out the screening, data extraction, and data analysis. The Cochrane risk of bias 1.0 tool was then used to assess the methodological quality of the eligible studies.

Sixteen studies met the inclusion criteria, with a total of 9,682 participants in the intervention arm and 10,115 in the control arm. Seven RCTs reported hepatotoxicity, with a significantly increased risk among patients treated with mAbs compared to those given SoC or placebo (risk ratio [RR], 1.70, 95 percent confidence interval [CI], 1.29–2.24). [Br J Clin Pharmacol 2025;91:1306-1321]

Five RCTs reported neutropenia and found a significant association with mAbs use compared with SoC or placebo (RR, 4.03, 95 percent CI, 1.74–9.34). Finally, 10 RCTs reported any disease-related serious adverse events and found a reduction of risk with mAbs, but this did not reach statistical significance (RR, 0.88, 95 percent CI, 0.70–1.11).

Medications

Tocilizumab (TCZ) was the most common mAb used in the selected RCTs. [N Engl J Med 2020;383:2333-2344; JAMA Intern Med 2021;181:32-40; N Engl J Med 2021;384:1491-1502]

Other mAbs used were sarilumab, imdevimab/casirivimab, sotrovimab, and bamlanivimab. [Lancet Respir Med 2021;9:522-532; Lancet 2022;399:665; JAMA 2022;327:1236-1246; J Emerg Med 2022;62:83-91; J Infect Dis 2023;227:23-34]

“The mAbs have emerged as powerful therapeutic options for the treatment of serious illnesses involving immune-mediated responses as significant pathogenetic mechanisms,” the researchers said. 

“Hence, it was not surprising that the use of mAbs emerged as one of the therapeutic options in the treatment of severe COVID-19 infection which involved immune-mediated surge in the production of several cytokines resulting in severe and sometimes fatal inflammatory reactions manifesting as respiratory and nonrespiratory consequences,” they added. 

“Due to the neutralizing properties, the use of mAbs in COVID-19 aimed to suppress the immune-mediated inflammatory reaction either by targeting the virus or the inflammatory cytokines,” according to the researchers.

Several studies have since reported the benefits of treatment with mAbs, but these studies also recognize the adverse effects of such medications. [Cell 2021;184:3086-3108; Clin Exp Med 2021;21:167-179; Annu Rev Med 2022;73:1-16; J Biomed Sci 2022;29:1]

“Since the majority of mAbs were investigational agents and had obtained approval with EUA during the pandemic, in this study, we investigated the reported adverse effects of different mAbs from a clinical point of view regardless of the mechanisms of actions of the individual drug,” the researchers said. 

“To the best of our knowledge, not all adverse drug reactions may be directly explainable by the known mechanisms of actions of medications,” they added.