Tixagevimab and cilgavimab use in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder during anti-CD20 treatment: A single-center experience.

Background: B-cell-depleting treatments, such as ocrelizumab and rituximab (anti-CD20), reduce humoral response to SARS-CoV-2 in people with Multiple Sclerosis (pwMS) and Neuromyelitis Optica Spectrum Disorder (NMOSD) and are associated with an increased risk of a more severe course of COVID-19 disease. The combination of tixagevimab and cilgavimab was authorized for COVID-19 prevention in immunocompromised subjects at high risk of severe COVID-19 disease, including patients treated with anti-CD20. Few real-world studies are available regarding the use of tixagevimab/cilgavimab in pwMS/NMOSD. In the present study, we describe the use of tixagevimab/cilgavimab for SARS-CoV-2 pre-exposure prophylaxis in a cohort of pwMS and NMOSD, treated with ocrelizumab and rituximab respectively.

Methods: 26 subjects were treated with tixagevimab/cilgavimab, while we used 18 patients as the control group. We collected clinical data at baseline in all patients and during scheduled follow up evaluations. SARS-CoV-2 serological status pre- and post-tixagevimab/cilgavimab treatment was available for 10 patients.

Results: We observed no adverse events following tixagevimab/cilgavimab treatment. Post-tixagevimab/cilgavimab anti-Spike-1-RBD IgG were significantly higher when compared to baseline values. No difference was found when comparing the percentage of COVID-19 infections between groups. All patients infected with SARS-CoV-2 had mild disease which did not require hospitalization. In patients treated with tixagevimab/cilgavimab, the rate of infection among patients exposed to SARS-CoV-2 was lower, without reaching statistical significance. We observed a significantly longer negativization time in the treated group.

Conclusions: Our results are not consistent with what was observed in the registration trial and some more recent studies. We did not observe a difference in COVID-19 incidence nor in disease severity in MS and NMOSD between treated and untreated patients. Our different results may be partially explained by the change in SARS-CoV-2 variants epidemiology (i.e. reduced efficacy of tixagevimab and cilgavimab against the currently dominant variants) as well as different patient selection included in the trial and different dose of tixagevimab/cilgavimab used in other studies. The present report provides a real-life experience with tixagevimab/cilgavimab in pwMS and NMOSD treated with anti-CD20, with findings that are in line with the current SARS-CoV-2 epidemiology and the recent evidence regarding SARS-CoV-2 variants. Our results warrant further research to best treat patients in the present and future pandemic scenario.