TIME between SECOND and THIRD DOSES INFLUENCES RESPONSE to COVID-19 VACCINE in AUTO-IMMUNE DISEASE PATIENTS TREATED with RITUXIMAB WITHOUT RESPONSE to TWO DOSES

ABSTRACT

Background: It is now well established that patients treated with rituximab (RTX) for auto-immune disease (AID) have a diminished antibody response to COVID-19 vaccines after two doses. Optimizing antibody response is a key objective in this population. To achieve this goal, a 3rd booster dose may be considered. Objectives: Focusing on the population of AID patients treated with RTX without any antibody response after two doses we sought to explore how these patients could respond to a 3rd dose and identify factors of response. Methods: We performed a French retrospective bicentric observational trial which is a follow up of previously published work (1). We included consecutive patients treated with RTX that were non-responders regarding their anti-Spike antibody (anti-S) status at least one month after the second dose of COVID-19 vaccination. Patients were included between March and October 2021. All patients then received a third dose according to local guidelines and had an anti-S measurement at least one month after the third dose. Some patients without response to a third dose had a fourth dose. Anti-S were measured in serum with various kits, but all results were in BAU/mL with upper quantifcation limit at 243. Patients with anti-S above 49 BAU/mL, which has been demonstrated to be the threshold associated with detectable neutralizing response were considered as responders (1). Results: 60 patients treated with RTX without response to 2 doses (Anti-S Ab < 49 BAU/mL) were included in the study. 9/60 (15%) patients responded to the 3rd vaccine dose with anti-S > 49BAU/ml. Responders and non-responders had similar demographic characteristics (Table 1). There was a positive correlation between anti-S Ab levels after dose 3 and time between 2nd and 3rd doses (r=0,41 p=0,001) (Figure 1). Nevertheless, the median time between 2nd and 3rd doses was numerically but not signifcantly higher in responders than in non-responders (129 vs 80 days, p=0.30). There was no correlation between anti-S levels after the third dose and the time between the last RTX infusion and the third vaccine dose. There was a trend towards more patients with methotrexate co-medication in the non-responder group 31/51 (61%) vs 3/9 (33%) in the responder group (p=0,15). Seven non-responder patients after the 3rd dose received a 4th dose and 4 (57%) responded. Conclusion: A third vaccine dose of COVID-19 vaccine leads to only 15% of response in previously non-responding RTX treated AID patients. A longer time between 2nd and 3rd doses might positively influences response to a 3rd COVID-19 vaccine. Finally exploratory fndings show that a fourth dose could be useful to obtain response non-responders.