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Despite enhanced dosing schedules, the effectiveness of SARS-CoV-2 vaccines remains diminished in those who are immunosuppressed (NEJM JW Infect Dis Oct 2021 and N Engl J Med 2021 Aug 11 [e-pub]; NEJM JW Infect Dis Jul 2021 and multiple citations). Thus, these individuals (an estimated 3% of the U.S. population) require alternative means of protection against COVID-19. The monoclonal antibodies tixagevimab and cilgavimab (co-packaged as Evusheld) bind to non-overlapping regions of the spike protein receptor binding domain and have a half-life of just under 3 months. In an ongoing placebo-controlled trial involving >5000 high-risk participants, active treatment led to a 77% relative risk reduction in symptomatic COVID-19 (Evusheld, 0.2%; placebo, 1.0%).
Authorized population: The EUA specifies use of Evusheld as preexposure prophylaxis in those aged ≥12 years who weigh ≥40 kg. Patients must have moderate or severe immunocompromise resulting from qualifying conditions or receipt of immunosuppressive treatments. Use is allowed in those with allergic reactions to COVID-19 vaccines and is not authorized for post-exposure prophylaxis or treatment of COVID-19.
Dosing and Administration: Tixagevimab and cilgavimab are administered as two intramuscular injections. Additional doses may be given at 6-month intervals (although supporting data are not yet available). No dosing adjustment for renal or hepatic dysfunction is required. A postadministration observation period of 1 hour is recommended.
Safety and Drug Interactions: One case of anaphylaxis shortly after administration was reported. Increased risk for cardiac adverse events (including myocardial infarction) was observed, all in participants with a history of cardiac disease. No drug interactions are expected.
U.S. Food & Drug Administration.Dec. 10, 2021. Evusheld EUA Letter of Authorization (https://www.fda.gov/media/154704/download)
Comment
I had eagerly awaited the authorization of this antibody combination to provide additional protection to immunocompromised patients who cannot rely on vaccination. My enthusiasm has since been somewhat tempered by concerns about the preparation's limited supply as well as its activity against variants such as Omicron. Patients with the poorest predicted response to vaccination should be prioritized, including those on B-cell depleting therapies (e.g., rituximab) and those with multiple myeloma or chronic lymphocytic leukemia on active therapy. Other risk factors for severe disease and SARS-CoV-2 exposure also should be considered in triage decisions. The role of serological testing to determine eligibility remains unclear. Most importantly, this agent should not be viewed as an alternative to vaccination, but rather an adjunctive option for those expected to mount insufficient responses to vaccination.