P605 Immunogenicity and safety of standard and third dose SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases; a prospective cohort study
Authors: Jørgensen K K , Syversen S W , Jyssum I , Tveter A T , Tran T T , Sexton J , Provan S A , Mjaaland S , Warren D J , Kvien T K , Grødeland G , Nissen-Meyer L S , Ricanek P , Chopra A , Andersson A M , Kro G B , Jahnsen J , Munthe L A , Haavardsholm E A , Vaage J T , Lund-Johansen F , Goll G L 
Published: January 2022

Abstract

Background
The immunogenicity and safety following standard two-dose SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) are not well characterised, and data on third dose vaccination in this patient group are currently lacking.

Methods
This prospective, observational cohort study included adult patients on immunosuppressive therapy for Crohn’s disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and healthy controls receiving standard two-dose SARS CoV-2 vaccination. Patients with a weak serologic response (&lt;100 AU/ml) were allotted a third vaccine dose. Serum samples were collected prior to, and after vaccination for analyses of antibodies to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The aim of the study was to evaluate the immunogenicity and safety following standard and three dose SARS-CoV-2 vaccination in IMID patients on immunosuppressive therapies.

Results
A total of 1641 patients (280 CD, 195 UC, 566 RA, 305 SpA, 295 PsA, median age 52 [IQR 40–63], 899 [55%] women), and 1114 healthy controls (median age 43 [IQR 32–55], 854 [77%] women), were included in the study. After standard SARS-CoV-2 two dose vaccination, 1504 (91%) patients compared to 1096 (98%) healthy controls (p&lt;0,001) were responders. Anti-RBD levels were lower in patients (median 619 AU/ml [IQR 192–4191]) than controls (median 3355 AU/ml [IQR 896–7849]), p&lt;0,001. Response was shown in ≥90% of patients receiving methotrexate, tumor necrosis factor inhibitor (TNFi) monotherapy, ustekinumab, tozilizumab and vedolizumab, in 80–90% of patients receiving TNFi combination therapy and secukinumab and in ≤ 80% for JAK inhibitors (78%), and abatacept (53%) (Fig 1). Lower age (OR 0.96 [95% CI 0.95–0.98]) and receiving the mRNA-1273 vaccine (OR 5.4 [95% CI 2.4–11.9]) were predictors of response. Of 153 patients with a weak response receiving a third vaccine dose, 129 (84%) became responders. After standard two dose vaccination, adverse events (AE) were reported in 50% of patients and in 78% of controls, with a comparable safety profile. Following the third dose, 44% of patients reported AEs, without new safety issues emerging. No serious AEs were reported.

Conclusion
Response rate as well as anti-RBD levels were lower in IMID patients than healthy controls following standard vaccination. Third dose vaccination in serologically weak responders was safe and resulted in a response in most patients. Our data facilitate identification of patient groups at risk of an attenuated vaccine response eligible for post-vaccination serological monitoring. The data also support a third vaccine dose following standard SARS-CoV-2 vaccination to weak-responding IMID-patients.