THE PERSISTENCE of ANTI-SPIKE ANTIBODIES FOLLOWING TWO SARS-COV-2 VACCINES in PATIENTS with IMMUNE-MEDIATED INFLAMMATORY DISEASES USING IMMUNOSUPPRESSIVE THERAPY, COMPARED to HEALTHY CONTROLS

ABSTRACT

Background: Limited data is available regarding long-term effectiveness of SARS-CoV-2 vaccines in patients with immune-mediated infammatory diseases (IMIDs) on immunosuppressive therapy. Whether the persistence of vaccine-induced humoral immunity against SARS-CoV-2 differs between this patient population and the general public is currently unknown. Objectives: To compare the persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses between IMID patients using immunosuppressive medication and healthy controls and identify predictors of antibody decline. Methods: We included patients with infammatory joint-and bowel diseases on immunosuppressive medication and healthy controls enrolled in the prospective observational Nor-vaC study. Serum samples were collected at two time points following two dose SARS-CoV-2 vaccination (frst assessment within 6-48 days and second within 49-123 days). Sera were analysed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Anti-RBD <200 BAU/ml were defned as low levels. The estimated percent reduction in anti-RBD standardised to 30 days was calculated and factors associated with reduction were identifed in multivariable regression models. Results: A total of 1097 patients (400 rheumatoid arthritis, 189 psoriatic arthritis, 189 spondyloarthritis, 129 ulcerative colitis, 190 Crohńs disease) (median age 54 years [IQR 43-64];56% women) and 133 controls (median age 45 years [IQR 35-56];83% women) provided blood samples within the defined intervals (median 19 days [IQR 15-24] and 97 days [86-105] after second vaccine dose). Antibody levels were significantly lower in patients compared to controls at both assessments, with median anti-RBD 1468 BAU/ml [IQR 500-5062] in patients and 5514 BAU/ml [2528-9580] in controls (p<0.0001) and 298 BAU/ml [IQR 79-500] in patients and 715 BAU/ml [28-2870] in controls (p<0.0001), at first and second assessment respectively. Figure 1 show antibody levels at both assessments after medication group. At the second assessment, anti-RBD antibody levels decreased below 200 BAU/ml in 452 (41%) patients and in 1 (0.8%) control (p<0.0001) (Table 1). The percentage change in anti-RBD levels were-86 % in patients and-77 % in controls (p<0.0001). The majority of patients using rituximab had low antibody levels at both assessments, Figure 1. In the multivariable regression analyses, patients had a greater decline in anti-RBD levels compared to controls β-3.7 (95% CI-6.0,-1.4) (p<0.001). Use of tumor necrosis factor inhibitors in mono-or combination therapy was associated with the greatest decline compared to controls, β-6.1 (95% CI-8.1,-4.1) and β-6.4 (-8.4,-4.2) respectively (p<0.001). Conclusion: Within four months after the second vaccine dose, anti-Spike antibody levels declined considerably in both IMID patients and controls. Patients had lower antibody levels at the frst assessment and a more pronounced decline compared to controls, and were consequently more likely to have low antibody levels four months after the second vaccine dose. Our results support that IMID patients lose humoral protection and need additional vaccine doses sooner than healthy individuals.