TIME SINCE LAST RITUXIMAB TREATMENT IS ESSENTIAL FOR DEVELOPING A HUMORAL RESPONSE TO THE COVID-19 MRNA VACCINE IN PATIENTS WITH RHEUMATIC DISEASES.

BackgroundConcerns about Rituximab (RTX) treatment and potentially inadequate vaccine response were aired early in the pandemic, and initial data seem to support this concern (1). So far, studies regarding rheumatic patients and the COVID-19 vaccines have included a relatively small number of patients receiving rituximab.ObjectivesWe aimed to investigate if patients with rheumatic diseases treated with RTX raise a serological response towards the COVID-19 mRNA vaccines and to elucidate the influence of time since the last dose RTX before vaccination on this response.MethodsWe included 201 patients followed at the Department of Rheumatology, Aarhus University Hospital. All had been treated with RTX in the period 2017-2021, and had finished a two-dose COVID-19 mRNA vaccination. All patients and 44 blood donors had total antibodies against SARS-CoV2 spike protein measured. Univariate and multivariate logistic regression were used.ResultsPatients were predominantly female (67%) with a median age of 62 years. The most frequent diagnosis was ANCA-associated vasculitis (32%), rheumatoid arthritis (31%), and myositis (14%), and 97% had the Pfizer/Biontic vaccine. Median number of RTX infusions were 5 (IQR 2-8), with a cumulative dose of 4g (2-8), and 72% had received RTX within the last 15 months. Prednisone was used by 43%, followed by methotrexate (25%), hydroxychloroquine (11%) and azathioprine (10%).We observed a time-dependent increase in antibody response as the interval from the last RTX treatment to vaccination increased (Table 1). Only 17.3% of patients developed a detectable antibody response after receiving their vaccination 6 months or less after their previous RTX treatment (Figure 1). Positive antibody response increased to 66.7% in patients who had RTX 9-12 months before vaccination. Neither cumulative treatment time nor cumulative RTX dose seemed to influence the serological response to the vaccine (Table 1). Thus, even in patients who have received RTX for a substantial time, expanding time-since-last-RTX treatment could prove beneficial for increasing the chance of a serological response. We further found that “months between last Rtx and vaccination”, prednisone and azathioprine treatment were alle negatively associated with antibody response in a multivariate logistic regression analysis(Table 1). All blood donors (100%) had detectable antibodies after vaccination.Table 1.Logistic regression analysis with precense of SARS-CoV-2 antibodies after mRNA vaccination as dependent varaible.UnivariateOR95% CIP-valueSex, female = ref.0.910.50 - 1.670.77Age, years0.980.96 - 1.000.09Diagnosis1.050.99 – 1.130.08Months between last RTX and vaccination1.061.03 - 1.09<0.001Total number of RTX infusions0.960.92 - 1.010.10Total dose of RTX, mg0.970.92 - 1.020.18Time from first to last RTX treatment1.001.00 - 1.000.57No DMARD treatment0.940.50 - 1.780.85Prednisone, dose in mg0.910.85 - 0.990.02Methotrexate1.710.90 - 3.250.10Hydroxychloroquine0.870.35 - 2.190.77Azathioprine0.230.06 - 0.800.02Multivariate modelMonths between last Rtx and vaccination1.081.04 - 1.11<0.001Prednisone treatment, mg0.910.84 - 0.990.03Azathioprine treatment0.100.02 - 0.440.002All significant variables in the univariate analysis were included in the multivariate model.ConclusionIn conclusion, patients with rheumatic diseases treated with RTX have a severely impaired serological response towards the COVID-19 mRNA vaccine. This is especially true if the interval between RTX treatment and vaccination is less than 9 months. For the majority of RTX treated patients, the recommended six months since last RTX is insufficient to develop a humoral response to COVID-19 mRNA vaccines. Our data suggest that the current recommendations of a 6 months interval should be revised.References[1]Ammitzbøll C, et al. Impaired antibody response to the BNT162b2 mRNA COVID-19 vaccine in patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis. ACR Open Rheumatol. 2021;Disclosure of InterestsNone declared