Hines, IL—Vaccines have been highly successful at preventing the spread of SARS-CoV-2 and decreasing the likelihood of severe disease in the general population; however, persons who are immunocompromised still face a greater danger of breakthrough infections and persistent viral replication.

That is why the FDA granted an Emergency Use Authorization (EUA) for tixagevimab/cilgavimab in December 2021. The combination was approved as preexposure prophylaxis for moderately to severely immunocompromised individuals and in those for whom vaccination with any available COVID-19 vaccine is not recommended due to a history of severe adverse reactions.

Approval was based on the PROVENT study, a phase III, multicenter, randomized, placebo-controlled trial. The study demonstrated that a single IM dose of tixagevimab/cilgavimab significantly reduced the incidence of symptomatic SARS-CoV-2 infection by 76.7% after 90 days in a varied group of adults with an increased risk of inadequate response to vaccination and/or increased risk of exposure to SARS-CoV-2.

A recent report in mBio pointed out, however, that while the PROVENT trial also included patients with chronic health conditions that could predispose them to COVID-19 complications, only 11% of the trial participants were immunocompromised (defined as being on immunosuppressive therapy or having an immunosuppressive disease or cancer).

Researchers from the U.S. Department of Veterans Affairs, Pharmacy Benefit Management, Center for Medication Safety in Hines, Illinois, and colleagues explained that “treatment effectiveness in this crucial subgroup could not be estimated in the trial. Furthermore, all participants in the PROVENT trial were unvaccinated at the time of trial entry; therefore, indications for tixagevimab/cilgavimab among vaccinated persons remain unknown.”

Because the follow-up of participants in the PROVENT trial ended in September 2021, the authors suggested that “an analysis regarding ‘real-world’ effectiveness is needed for tixagevimab/cilgavimab among vaccinated immunocompromised veterans after the emergence of the Omicron variant,” which occurred in December 2021 in the United States.

The retrospective cohort study included immunocompromised patients as of January 1, 2022, who were receiving VA healthcare. The study team compared a cohort of 1,878 patients treated with at least one dose of IM tixagevimab/cilgavimab with 7,014 matched controls selected from patients who met study criteria but were not treated.

Patients were followed through June 15, 2022, or until death, whichever occurred earlier, and the primary outcome was defined as a composite of SARS-CoV-2 infection, COVID-19-related hospitalization, and all-cause mortality.

Most (73%) of the tixagevimab/cilgavimab recipients were aged 65 years and older, with 80% having had three or more mRNA-vaccine doses or two doses of Ad26.COV2.

“Compared to matched controls, recipients had a lower incidence of the composite COVID-19 outcome (49/1,878 [2.6%] versus 312/7,014 [4.4%]; HR 0.35; 95% CI, 0.24–0.52), and individually SARS-CoV-2 infection (HR 0.44; 95% CI, 0.22–0.88), COVID-19 hospitalization (HR 0.24; 95% CI, 0.10–0.59), and all-cause mortality (HR 0.32; 95% CI, 0.19–0.55),” the researchers pointed out, adding, “In conclusion, tixagevimab/cilgavimab was associated with lower rates of SARS-CoV-2 infection and severe COVID-19 during the Omicron BA.1, BA.2, and BA.2.12.1 surge.”

Background information in the report advised that the fast-tracking of medications to help mitigate the COVID-19 pandemic means that clinical trials have been limited. That “created the need to a real-world analysis, using electronic health record data, of the effectiveness of tixagevimab/cilgavimab for the prevention of COVID-19 infection in the unique population of U.S. veterans. Unlike those in the PROVENT clinical trial from which the EUA for tixagevimab/cilgavimab as a preventative treatment arose, the veteran population is highly immunocompromised and nearly 96% totally vaccinated.”

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

 « Click here to return to Weekly News.