POS1227 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

BackgroundIt 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.ObjectivesFocusing 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.MethodsWe 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 quantification 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).Results60 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 significantly 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.Table 1.Characteristics of patients without response after the second dose of vaccine treated with Rituximab for auto-immune diseases according to their seroconversion status after the third dose.Non responders (n=51)Responders (n=9)pAge, median (min-max)61 (17-85)58 (36-78)0,33Female sex n (%)42 (82)6 (67)0,36Underlying disease n (%) Rheumatoid Arthritis36 (69)5 (56)0,46 Other auto-immune disease16 (31)4 (44)Rituximab treatmentReceived a RTX infusion between dose 2 and 3 n (%)14(27)3(33)0,70Time between the last RTX infusion and the 3rd dose of vaccine in days median (min-max)162 (1-687)187 (79-959)0,16Previous number of RTX injections, median (min-max)7 (0-34)6 (1-22)0,58Vaccination schemeInterval between 2nd and 3rd vaccine dose in days, median (min-max)80 (23-287)129 (24-220)0,30Less than 3 months between 2nd and 3rd vaccine dose n (%)27(53)2(22)0,14Co-medicationsPatients on steroids n (%)20(40)5 (37,5)0,99Prednisone equivalent dose per day in mg median (min-max)5(2-25)5(5-10)0,48Figure 1.Correlation between anti- spike Ab levels after the third dose and time in days between doses 2 and 3.ConclusionA 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 findings show that a fourth dose could be useful to obtain response non-responders.