A recent article posted to the medRxiv* preprint server assessed the potency of tixagevimab/cilgavimab in averting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vaccinated immunocompromised people.
CoV disease 2019 (COVID-19) is associated with a high risk of mortality and morbidity in immunocompromised people. While COVID-19 vaccines have helped halt SARS-CoV-2 spread and reduce the risk of severe illness in the general population, immunocompromised persons are still at high risk of continuous viral replication and breakthrough infections.
A Phase III, randomized, placebo-controlled, multicenter trial, the PROVENT investigation, showed a single intramuscular tixagevimab/cilgavimab dose substantially decreased symptomatic COVID-19 incidence by 76.7% following 90 days in a large sample of adults with an elevated risk of insufficient vaccination response or SARS-CoV-2 exposure.
Relying on these results, on 8 December 2021, the United States (US) Food and Drug Administration (FDA) provided tixagevimab/cilgavimab an emergency use authorization (EUA) as a pre-exposure prophylactic for moderate or severely immunocompromised people or for whom vaccination with any existing SARS-CoV-2 vaccine is not advised because of a severe adverse reaction history. However, the efficacy of tixagevimab/cilgavimab in preventing COVID-19 in vaccinated immunocompromised individuals is uncertain, especially following the emergence of the SARS-CoV-2 Omicron strain.
About the study
The present retrospective cohort research aimed to investigate the efficacy of tixagevimab/cilgavimab in preventing COVID-19 and severe SARS-CoV-2 infection across COVID-19 vaccinated immunodeficient patients via difference-in-difference analyses (DiD) and propensity matching. The study was performed using the electronic data from the Department of Veterans Affairs (VA) healthcare system in the US, the most comprehensive healthcare network in the US, of Veterans aged 18 or older as of 1 January 2022 who were getting VA medical care.
The researchers compared a group of 1,848 patients who received a minimum of one intramuscular dose of tixagevimab/cilgavimab with matched controls identified from 251,756 patients who were immunodeficient or were at increased risk for SARS-CoV-2 infection. Patients were monitored through 30 April 2022 or till death, whichever came first. The investigation's key outcomes were a COVID-19 composite, SARS-CoV-2-linked hospitalization, and all-cause death. The team employed Cox proportional hazards modeling to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for the link between tixagevimab/cilgavimab use and outcomes.
On the whole, in the current study, the scientists determined the real-world efficacy of tixagevimab/cilgavimab in preventing COVID-19, SARS-CoV-2-related hospitalization, and all-cause death in COVID-19 vaccinated immunocompromised Veterans.
Findings and discussions
Overall, the study results showed that 69% of Veterans who received tixagevimab/cilgavimab were 65 years or older, 92% were recognized as immunodeficient by electronic data, and 73% got ≥ three doses of COVID-19 messenger ribonucleic acid (mRNA) vaccine or two Ad26.COV2 doses. Before receiving tixagevimab/cilgavimab, almost all (95%) of the study participants had received a minimum of two COVID-19 mRNA vaccine doses or one Ad26.COV2 dose.
Tixagevimab/cilgavimab-treated patients had a notably decreased occurrence of the composite SARS-CoV-2 infection outcome (17/1733 versus 206/6354), as well as COVID-19, SARS-CoV-2-associated hospitalization, and all-cause death relative to propensity-matched controls. The present results were invariant over two robust statistical techniques, including DiD estimations and propensity score matching.
Since these findings were observed among moderate to severely immunocompromised and older patients, they backed up the EUA guidelines for tixagevimab/cilgavimab use in this cohort. The investigators discovered that fully vaccinated (at least two doses) immunocompromised patients administered tixagevimab/cilgavimab had enhanced protection against COVID-19, similar to fully boosted (primary vaccination regimen plus a booster dose) non-immunocompromised adults.
While tixagevimab/cilgavimab retained neutralization against the SARS-CoV-2 Delta variant, they had a lower neutralizing effect against the Omicron BA.1 variant, urging the FDA to revise the EUA to increase tixagevimab/cilgavimab's initial dose. Further, current evidence illustrated that tixagevimab/cilgavimab retained neutralization against Omicron BA.2.12.1 and BA.2 variants, albeit their efficacy might be diminished with Omicron BA.5 and BA.4 strains. In addition, the authors noted that the trial had immortal time bias and indication confounding.
According to the scientists, this research offered the initial real-world proof of tixagevimab/cilgavimab's potential in preventing SARS-CoV-2 infection and valuable information about the patient population who received tixagevimab/cilgavimab throughout the VA healthcare network.
Overall, in the present work, utilizing nationwide US real-world data from mostly vaccinated, immunodeficient Veterans, the authors found using tixagevimab/cilgavimab during the Omicron surge period was linked with diminished COVID-19, SARS-CoV-2-related hospitalization, and all-cause death rates. These results suggested that in addition to COVID-19 vaccination, tixagevimab/cilgavimab treatment safeguards susceptible individuals from COVID-19 and severe SARS-CoV-2 infection in the current phase of the pandemic.
The study showed that only a tiny percentage of eligible subjects received tixagevimab/cilgavimab therapy, implying that additional outreach and education were needed to ascertain that more immunodeficient Veterans throughout the VA healthcare network received tixagevimab/cilgavimab, notably during SARS-CoV-2 outbreaks. Besides, the authors stated that continued real-world data might aid in the understanding of tixagevimab/cilgavimab's effectiveness for pre-exposure COVID-19 prophylaxis across time and against new SARS-CoV-2 variants.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.