Efficacy of tixagevimab/cilgavimab as pre-exposure prophylaxis to prevent symptomatic COVID-19 infection in Multiple Sclerosis and Related Disorders: a real-world observational study (S31.010)

Abstract

<h3>Objective:</h3> To evaluate the risk of breakthrough symptomatic Coronavirus Disease 2019 (COVID-19) infections after tixagevimab/cilgavimab administration for pre-exposure prophylaxis in multiple sclerosis and related disorders (MSRD) patients on immunosuppressive therapy in real-world practice. <h3>Background:</h3> The use of a monoclonal-antibody combination tixagevimab/cilgavimab has been shown to be effective for pre-exposure prophylaxis in patients with risk factors for severe symptomatic COVID-19 infection. However, tixagevimab/cilgavimab effectiveness in MSRD patients on immunosuppressive therapy has not been comprehensively investigated. <h3>Design/Methods:</h3> Retrospective review of MSRD patients evaluated at the Cedars-Sinai Multiple Sclerosis and Neuroimmunology center between January 1, 2022, to October 10, 2022. Patient clinical characteristics, comorbidities, disease modifying therapy, COVID-19 vaccination status, tixagevimab/cilgavimab administration status, and symptomatic COVID-19 infection occurrence were evaluated. Propensity score matching using multivariable logistic regression was used to analyze the effect of tixagevimab/cilgavimab on breakthrough COVID-19 infection accounting for age, sex, race, disease modifying therapy, and COVID-19 vaccination. <h3>Results:</h3> A total of 348 MSRD patients were included in the analysis, among which 64 (18%) received tixagevimab/cilgavimab, and 284 (82%) did not (mean age 50±13 and 52±13 years, 80% and 69% female, respectively). Most common indications for tixagevimab/cilgavimab were anti-CD20 therapy (83%) and sphingosine-1-phosphate receptor modulator therapy (5%). Using propensity score matching, the probability of observing symptomatic COVID-19 infection in the tixagevimab/cilgavimab group was lower by 11.0% (p=0.01; 95% CI 3–19%). Breakthrough infections on tixagevimab/cilgavimab occurred in 4 cases (8%), 3 of which occurred in patients receiving medications suppressing B and T lymphocyte proliferation (two cases on mycophenolate mofetil, and one case with prior history of cyclophosphamide and mitoxantrone treatment). <h3>Conclusions:</h3> In this retrospective observational study, tixagevimab/cilgavimab injection was associated with a lower incidence of symptomatic COVID-19 infection in MSRD patients on immunosuppressive therapy. Breakthrough COVID-19 infections on tixagevimab/cilgavimab were observed in patients with current or prior exposure to medications suppressing B and T lymphocyte proliferation. <b>Disclosure:</b> Dr. Tan has nothing to disclose. Ms. Locke has nothing to disclose. The institution of Dr. Sati has received research support from National Multiple Sclerosis Society. The institution of Dr. Sati has received research support from National Institutes of Health. Dr. Sati has received publishing royalties from a publication relating to health care. Dr. Guerrero has nothing to disclose. The institution of Dr. Sicotte has received research support from Biogen. The institution of Dr. Sicotte has received research support from PCORI. The institution of Dr. Sicotte has received research support from NIH. The institution of Dr. Sicotte has received research support from NMSS. Dr. Sicotte has a non-compensated relationship as a National Medical Advisory Committee Chair with National MS Society that is relevant to AAN interests or activities. The institution of Dr. Al-Louzi has received research support from the National Multiple Sclerosis Society and American Brain Foundation.