Pre-exposure prophylaxis of COVID-19 with tixagevimab/cilgavimab (Evusheld) in 63 rituximab-treated patients with ANCA-associated systemic vasculitis: two-year follow-up results

Patients with ANCA-associated systemic vasculitis (AAV) are at risk of severe COVID-19. At the same time, in immunocompromised patients, in particular those receiving anti-B cell therapy with rituximab (RTX), the post-vaccination effect may be insufficient. Since 2022 the long-acting virus-neutralizing monoclonal antibodies (MAB) tixagevimab and cilgavimab (Evushheld, AZD7442) have been used as pre-exposure prophylaxis for COVID-19. The aim of the study is to evaluate the effectiveness of tixagevimab and cilgavimab (TC) for pre-exposure prophylaxis of COVID-19 and its safety in RTX treated patients with AAV. Materials and methods . The prospective study included 63 patients with AAV receiving RTX. Median age 53 (19– 79) years, M:F 1:1.1. From March 2022 to June 2023, TC was administered in a total dose of 300 mg and/or 600 mg. Observation continued until April 2024. In November 2023 and in April 2024 a telephone and/or online survey was conducted simultaneously to identify confirmed cases of COVID-19 and adverse reactions. The survey also included the Treatment Satisfaction Questionnaire version 9 (TSQM-9). Considering the duration of the TC effect (6 months), COVID-19 cases were divided into two groups depending on the interval after the last administration of the TC: up to 6 months inclusive – group 1; more than 6 months – group 2. Results . During the two-year follow-up period, confirmed COVID-19 was detected in 31.7% patients, the median interval between the last TC administration and the development of COVID-19 was 5.5 [2–19] months. In group 1, which included 12 cases of COVID-19, 92% of patients had a mild form of the disease, only one had lung damage, and there were no fatal outcomes. In group 2, COVID-19, detected after the cessation of the TC effect in 9 patients, was accompanied by lung damage in 89% of cases, required hospitalization in 78%, and fatal in two patients. Four patients had a prolonged course of severe COVID-19 with persistence of SARS-CoV-2 (pCOVID, persistent COVID). In 4 cases, including 3 cases with pCOVID, treatment was carried out with the combined antiviral drug nirmarelvir + ritonavir (Skyvira) in combination with intravenous human immunoglobulin (IVIG) with effect. There were no statistically significant differences in the incidence of COVID-19 in patients with secondary immunodeficiency and without it (p=0.868). At the final stage of the study, the serum level of IgG antibodies to SARS-CoV-2 was examined in 34 patients, its median was 70.4 (0.33–1086.1) binding antibody units (BAU), which indicates a lack of neutralizing antibodies in most patients; there were no statistical differences in their level between patients with and without COVID-19 (p=0.685). No adverse reactions directly related to the use of TC were observed. A high level of the TSQM-9 global treatment satisfaction domain was noted with a median 71.4 (14.3–100); 72,4% of respondents answered “satisfied”– “extremely satisfied” to the first question of TSQM-9 (effectiveness domain). Conclusions . Pre-exposure prophylaxis of COVID-19 using TC in patients with AAV receiving RTM was safe and allowed to reduce the risk of severe COVID-19 and avoid deaths during the period of TC action. After the cessation of TC, an increase in the frequency of severe COVID-19 with the need for hospitalization and deaths was observed, cases of pCOVID were noted. The use of a combination of Skyvira and IVIG for the treatment of pCOVID was effective in all cases. The use of MAB for pre-exposure prophylaxis of COVID-19 in patients with AAV and other rheumatic diseases requires further in-depth study.