Tixagevimab and Cilgavimab (Evusheld™) Prophylaxis Prevents Breakthrough COVID-19 Infections in Immunosuppressed Population: 6-Month Prospective Study

Abstract

Background: Persons with neuroinflammatory diseases (pwNID) treated with potent immunosuppressives are at risk of severe COVID-19 outcomes and reduced vaccine seroconversion. We aimed at determining the real-world efficacy of tixagevimab and cilgavimab (Evusheld™) in immunosuppressed pwNID in preventing breakthrough COVID-19 infections. Methods: 31 immunosuppressed pwNID were followed for 6 months after administration of tixagevimab and cilgavimab as a prophylactic COVID-19 medication (January 2022–July 2022). Only pwNID treated with anti-CD20 monoclonal antibodies and sphingosine-1-phosphate modulators were considered eligible for the study. A control group of 126 immunosuppressed pwNID (38 seropositive and 88 seronegative after SARS-CoV-2 vaccination) were included. Breakthrough COVID-19 infections rate and their severity was determined over the follow-up. Results: The pwNID treated with tixagevimab and cilgavimab had more comorbidities when compared with the total and seronegative pwNID control group (54.8% vs. 30.2% vs. 27.3%, p = 0.02 and p = 0.005, respectively). After a 6-month follow-up, significantly lower numbers of pwNID treated with tixagevimab and cilgavimab had breakthrough COVID-19 when compared with the control pwNID group (6.5% vs. 34.1%, p = 0.002) and seronegative control pwNID group (6.5% vs. 38.6%, p < 0.001). All COVID-19 infections in Evusheld-treated pwNID were mild, whereas 9/43 COVID-19 infections in the control group were moderate/severe. No side effects to tixagevimab and cilgavimab were recorded. Conclusion: In pwNID treated with immunosuppressive therapies, tixagevimab and cilgavimab (Evusheld™) significantly reduced the numbers and severity of breakthrough COVID-19 infections during the Omicron (BA.2–BA.5 variants) wave.

Tixagevimab/cilgavimab in ANCA-associated vasculitis: a prospective observational study

“…To our knowledge, this is the first prospective study that followed the patients with AAV after tixagevimab/cilgavimab administration. Our data confirm a good safety profile and potential efficacy of tixagevimab/cilgavimab in immunosuppressed AAV patients and are consistent with previously published studies (6)(7)(8). The limitations of our study include a small sample size, absence of a control group and administration of tixagevimab/ cilgavimab at a lower dose than currently recommended.…”

Tixagevimab/Cilgavimab as Pre-Exposure Prophylaxis against COVID-19 for Multiple Myeloma Patients: A Prospective Study in the Omicron Era

“…A systematic review and meta-analysis of the protective properties of the monoclonal antibody combination, including patients with hematological malignancies in the Omicron era, also highlighted its clinical effectiveness [ 50 ]. A 6-month prospective study on 31 immunocompromised patients receiving immunosuppressive therapy reported that Evusheld significantly reduced the severity of breakthrough COVID-19 infections during the BA.4 and BA.5 Omicron wave [ 51 ]. A single-center retrospective study analyzing clinical outcomes of patients with hematological malignancies who were administered tixagevimab/cilgavimab for COVID-19 prevention or treatment generated beneficial results [ 52 ].…”

Measures to Increase Immunogenicity of SARS-CoV-2 Vaccines in Solid Organ Transplant Recipients: A Narrative Review

“…In vitro studies have shown the reduced neutralization ability of tixagevimab–cilgavimab to Omicron BA.1 and BA.2, and even more reduced neutralization to recent variants such as BQ 1.1 and XBB 1.5 [ 119 ]. Another in vitro study showed that, while tixagevimab–cilgavimab continued to inhibit BA.2.12.1, BA.4, and BA.5, the titers needed to achieve an equivalent level of inhibition (50% neutralization) for BA.5 were approximately 30.7 times higher than those required for the ancestral strain [ 120 ]. Nevertheless, the previously mentioned clinical data continued to demonstrate the effectiveness of tixagevimab–cilgavimab during the Omicron wave [ 112 , 113 , 114 , 115 ].…”