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.

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.

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.

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).

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.