OP0177 IMMUNOGENICITY INDUCED BY TWO AND THREE DOSES OF THE BNT162B2 mRNA VACCINE IN PATIENTS WITH AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES AND IMMUNOCOMPETENT CONTROLS: A LONGITUDINAL MULTI-CENTER STUDY

Abstract

Background: Data on the kinetics of the immune response to SARS-CoV-2 vaccination in patients with autoimmune infammatory rheumatic diseases (AIIRD) are limited. Objective(s): To evaluate the kinetics of the immune response induced by two and three doses of the BNT162b2 mRNA vaccine in adult patients with AIIRD and immunocompetent controls. Method(s): A prospective multicenter study investigated the antibody response to the BNT162b2 vaccine by serial measurement of serum anti-SARS-CoV-2 S1/S2 IgG titers at the following time points: 2-6 weeks (AIIRD n=720, controls n=122) and six months (AIIRD n=628, controls=116) after the second vaccine dose, and 2-6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). A seropositive response was defned as a detectable anti-S1/S2 IgG titer >= 15 BAU/ml. T-cell immune response was evaluated in a sample of patients (n=28) and controls (n=9) by intracellular staining of S-stimulated CD4+ T-cells for TNFalpha and IFNgamma production. Result(s): The two-dose vaccine regimen induced a higher humoral response in controls compared to patients, as refected by the post-vaccination seroposi-tivity rates of 100% vs 84.72%, p<0.0001, and 96.55% vs 74.26%, p<0.0001 at 2-to-6 weeks and at 6 months, respectively. The decline of S1/S2 IgG titers within six months was similar in controls and patients. Following the 3rd vaccine, the seropositivity rate increased to 80.47% and 100% in AIIRD and control groups, p=0.0028, with a signifcantly higher increase of S1/S2 IgG titers in controls compared with AIIRD patients, 284.09+/-76.58 vs 219.39+/-151.55 BAU/ml, p=0.0016. At all-time points, S1/S2 IgG titers were signifcantly lower in AIIRD patients compared with controls (Figure 1). We further investigated the impact of therapies on the vaccine's immuno-genicity (Figure 1). Glucocorticoids (GC) were associated with a significantly lower seropositivity rate and lower S1/S2 IgG titers compared to controls at all time points. Monotherapy with methotrexate (MTX) was associated with a comparable to controls humoral response at all time points. Anti-cytokine biologics (TNFi, IL6i, IL17i) were associated with an initial high seropositivity rate, similar to controls, followed by a steeper decline at 6 months, 79.82% vs 96.55%, p=0.0001, and restoration of seropositivity after the 3rd vaccine dose in all patients. JAKi were associated with a mildly decreased seroposi-tivity rate after the 2nd vaccine dose and similar to controls response after the 3rd vaccine dose. Abatacept was associated with a reduced immunogenicity after the 2nd vaccine dose, but was restored to 100% seropositivity after the 3rd vaccine dose. Rituximab (RTX) significantly blunted the humoral response at all time points, with a seropositivity rate of 42% after the 2nd vaccine dose, 29% at 6 months, and with increase to 40% after the 3rd vaccine dose. A third of the RTX-treated patients who were seronegative after two vaccine doses, seroconverted after the 3rd dose. The multivariate model for predicting the seropositive response to vaccination found that higher S1/S2 IgG titers after the 2nd vaccine dose was associated with a higher seropositivity rate following the 3rd vaccine dose, OR 1.026 (1.008-1.045), p=0.0027, and that treatment with RTX was associated with a 14.3-fold risk for a negative humoral response, p