Evusheld Increased Attenuated SARS-CoV-2 Antibodies From MS B-Cell Depleting Medications

William L. Conte, MD, MS

Findings from a single-center cohort study showed that all patients with multiple sclerosis (MS) who had an attenuated response to SARS-CoV-2 vaccines due to B-cell depleting therapeutics developed the highest antibody response following treatment with Evusheld (AstraZeneca).¹

Evusheld, a combination of tixagevimab and cilgavimab, was approved by the FDA for emergency use for treating the pre-exposure prophylaxis of COVID-19 in certain adults and pediatric individuals. The product, authorized for those not currently infected with the virus, requires that individuals either have moderate to severely compromised immune systems due to a medical condition or a history of severe adverse reactions to a COVID-19 vaccine.

Led by William L. Conte, MD, MS, neurologist, Comprehensive MS Center, Methodist Hospitals, the small-scale study enrolled 18 patients with MS who were vaccinated against SARS-CoV-2 and were exposed to B-cell depleting medications during their vaccination period. Patients were tested for antibodies against the virus, and if they demonstrated less than 150 U/mL, or 50% of the maximum assay value, they were offered Evusheld. More specifically, they received 150 mg of tixagevimab and 150 mg of cilgavimab intramuscularly, which was administered prior to the FDA’s update to 300 mg each of the 2 agents.

Of the cohort, 17 were on ocrelizumab (Ocrevus; Genentech) and 1 on ofatumumab (Kesimpta; Novartis). Detection of immunoglobulin antibodies was performed using the Labcorp SARS-CoV-2 semiquantitative IgG ECLIA assay, which ranged from less than 0.4 U/mL to more than 250 U/mL. Titers of less than 0.8 U/mL were considered negative. At baseline, there were 12 patients lower than the 0.8 U/mL and 6 higher than the threshold, with an overall mean antibody level of 12.38 U/mL. At least 2 weeks following Evusheld injection, all patients developed an antibody response over 250 U/mL, which is the highest level the assay measures.

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Using the McNemar test, investigators observed significant differences in pre- and post-frequencies of samples higher or lower than 0.8 U/mL. When comparing the ranks of the level of antibodies pre and post treatment using a paired Wilcoxon test, there was a statistical difference (P <.001). To evaluate the difference further and see how extreme the change was prior and after Evusheld injection, a Permutation Test was performed, where the mean observed difference in the sample was 237.62, which was statistically significant (P <.001).

"It is concerning that certain medications, such as B-cell depleters, attenuate the antibody response to SARS-CoV-2. Therefore, it is important to have other options that do not depend on the humoral immune system,” Conte et al wrote. “As demonstrated in the data, we have shown that Evusheld creates a 100% antibody response in this patient population."

The National MS Society, a world leader in the MS community, has confirmed that Evusheld is safe to use with MS disease-modifying therapies. In addition to referencing Conte et al’s research, they note that those on sphingosine 1-phosphate receptor modulators, anti-CD20 monoclonal antibodies, and alemtuzumab (Lemtrada; Sanofi Genzyme), medications with potential reduced or absent immune response to COVID-19 vaccines, are qualified for Evusheld use.²

REFERENCES
1. Conte WL, Golzarri-Arroyo L. Tixagevimab and cilgavimab (Evusheld) boosts antibody levels in SARS-CoV-2 in patients with multiple sclerosis on b-cell depleters. Mult Scler Relat Disord. 2022;63:103905. doi:10.1016/j.msard.2022.103905.
2. Evusheld to Prevent COVID-19 in People With MS. National MS Society. https://www.nationalmssociety.org/coronavirus-covid-19-information/suspected-covid-19-and-ms/evusheld. Updated June 14, 2022. Accessed June 23, 2022.