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  1. I. Egeland Christensen1,
  2. I. Jyssum1,
  3. A. T. Tveter1,
  4. J. Sexton1,
  5. T. T. Tran2,
  6. S. Mjaaland3,
  7. G. B. Kro4,
  8. T. K. Kvien1,
  9. D. Worren5,
  10. J. Jahnsen6,
  11. L. A. Munthe2,
  12. E. Haavardsholm1,
  13. J. T. Vaage2,
  14. G. Grodeland2,
  15. F. Lund-Johansen2,
  16. K. K. Jørgensen6,
  17. S. W. Syversen1,
  18. G. L. Goll1,
  19. S. Aarrestad Provan1
  1. 1Diakonhjemmet Hospital, Division of Rheumatology and Research, Oslo, Norway
  2. 2Oslo University Hospital, Department of Immunology, Oslo, Norway
  3. 3Norwegian Institute of Public Health, Department of Infectious Disease Immunology, Oslo, Norway
  4. 4Oslo University Hospital, Department of Microbiology, Oslo, Norway
  5. 5Oslo University Hospital, Department of Medical Biochemistry, Oslo, Norway
  6. 6Akershus University Hospital, Department of Gastroenterology, Lørenskog, Norway


Background 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 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 inflammatory 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 (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.

Results A total of 1097 patients (400 rheumatoid arthritis, 189 psoriatic arthritis, 189 spondyloarthritis, 129 ulcerative colitis, 190 Crohn´s 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).

Table 1.

Serological response in patients and controls

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 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.

Disclosure of Interests Ingrid Egeland Christensen: None declared, Ingrid Jyssum: None declared, Anne Therese Tveter: None declared, Joe Sexton: None declared, Trung T. Tran: None declared, Siri Mjaaland: None declared, Grete B. Kro: None declared, Tore K. Kvien Speakers bureau: Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi, Consultant of: Abbvie, Amgen, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Sandoz, Sanofi, Grant/research support from: Grants to institution (Diakonhjemmet Hospital): Abbvie, Amgen, BMS, MSD, Novartis, Pfizer, UCB, David Worren: None declared, Jørgen Jahnsen Speakers bureau: AbbVie, Astro Pharma, Boerhinger Ingelheim, BMS, Celltrion, Ferring, Gilead, Hikma, Janssen Cilag, Meda, MSD, Napp Pharma, Novartis, Orion Pharma Pfizer, Pharmacosmos, Roche, Takeda, Sandoz, Consultant of: AbbVie, Boerhinger Ingelheim, BMS, Celltrion, Ferring, Gilead, Janssen Cilag MSD, Napp Pharma, Novartis, Orion Pharma, Pfizer, Pharmacosmos, Takeda, Sandoz, Unimedic Pharma, Grant/research support from: Abbvie, Pharmacosmos, Ferring, Ludvig A. Munthe Speakers bureau: Novartis, Cellgene, Espen Haavardsholm: None declared, John Torgils Vaage: None declared, Gunnveig Grodeland Speakers bureau: Bayer, Sanofi Pasteur, Thermo Fisher, Consultant of: Consulting fees from the Norwegian System of Compensation to Patients and AstraZeneca, Fridtjof Lund-Johansen: None declared, Kristin Kaasen Jørgensen Speakers bureau: Roche, BMS, Consultant of: Celltrion, Norgine, Silje Watterdal Syversen: None declared, Guro Løvik Goll Speakers bureau: AbbVie, Pfizer, UCB, Sandoz, Orion Pharma, Novartis, Consultant of: Pfizer, AbbVie, Sella Aarrestad Provan: None declared

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