The Persistence of Anti-Spike Antibodies Following Two Sars-Cov-2 Vaccines in Patients with Inflammatory Bowel- and Joint Diseases on Immunosuppressive Therapy Compared to Healthy Controls - a Prospective Cohort Study

ABSTRACT

Introduction: Limited data is available regarding long-term effectiveness of SARS-CoV-2 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy. Whether the persistence of vaccine-induced humoral immunity differs between IMID patients and the general public is currently unknown. Aims & Methods: IMID patients on immunosuppressive medication and healthy controls were enrolled in the prospective, observational Nor-vaC study. Serum samples were collected at two time points following two dose SARS-CoV-2 vaccination (first 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 defined as low levels. The estimated percent reduction in anti-RBD standardised to 30 days was calculated and factors associated with reduction were identified in multivariable regression models. The aims of the study were to compare the persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses between IMID patients and healthy controls, and to identify predictors of antibody decline. Result(s) A total of 1097 patients (190 Crohn's disease, 129 ulcerative colitis, 400 rheumatoid arthritis, 189 psoriatic arthritis, 189 spondyloarthritis) (median age 54 years [IQR 43-64];56% women) and 133 controls (age 45 years [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). Of the patients, 464 used tumor necrosis factor inhibitor (TNFi) monotherapy, 259 TNFi + metabolite inhibitor(s), 212 methotrexate monotherapy, 42 interleukin inhibitors, 34 vedolizumab, 29 rituximab, and 23 janus kinase inhibitors. 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. 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). The percentage change in anti-RBD levels were -86 % in patients and -77 % in controls (p<0.0001). In the multivariable regression analyses, patients had a greater decline in anti-RBD levels compared to controls beta -3.7 (95% CI -6.0, -1.4) (p<0.001). Use of TNFi in mono- or combination therapy was associated with the greatest decline compared to controls, beta -6.1 (95% CI -8.1, -4.1) and beta -6.4 (-8.4, -4.2) respectively (p<0.001). Conclusion(s) 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 first 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. (Table Presented).