Serologic Response to Sars-Cov-2 Vaccination in Patients with Inflammatory Bowel Disease on Immunosuppressive Therapy: Association to Disease Type and Serum Drug Levels

ABSTRACT

Introduction: Immune responses following SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) are not well characterised, and limited data is available regarding the humoral immune response related to the underlying bowel disease and serum concentrations of biologics and thiopurine metabolites. Aims & Methods: This prospective, observational study included adult patients with ulcerative colitis (UC) and Crohn's disease (CD), and healthy controls. Sera were analysed for antibodies binding the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein, and anti-RBD >=70 AU/ml was defined as serologic response. Anti-RBD and serum concentrations of the ongoing immunosuppressive medications were measured prior to, and 2-5 weeks after the second vaccine dose. The aims of this study were to explore the serologic response associated with the underlying bowel disease and immunosuppressive medications including serum concentrations of biologics and thiopurine metabolites. Result(s) The study included 958 IBD patients (380 UC, 578 CD), median age 40 (Q1;Q3 29;52), and 323 healthy controls, age 44 (33;56). The type and frequency of ongoing immunosuppressive therapy was comparable between the UC and CD patients. The median (Q1;Q3) anti-RBD level (AU/ml) was lower in patients (618 (192;4370)) compared to controls (3355 (896;7849)) post vaccination (p<0.001), and the antibody levels were lower in CD (439 (174;3304)) compared to UC (1088 (251;5975)) (p<0.001). No association between serum concentration and serologic response was demonstrated in patients treated with tumor necrosis factor inhibitor (TNFi) monotherapy, TNFi + thiopurines, vedolizumab, and ustekinumab. Patients treated with TNFi + thiopurines with low 6-thioguanine nucleotides (6-TGN) levels (<3.5 pmol/8x108RBC) demonstrated a higher response rate (93%) than patients who had 6-TGN levels within the therapeutic range (>=3.5 pmol/8x108RBC) (53%) (p=0.003). In the multiple regression model, UC as compared to CD, higher BMI, and mRNA-1273 vaccine were associated with higher odds for serologic response (Table). Older age and patients on treatment with TNFi + thiopurines were associated with lower odds ratios for a serologic response (Table). Treatment with TNFi monotherapy, disease activity (CRP, calprotectin, disease indices) gender and smoking were not associated with serologic response. Conclusion(s) No association between serum drug concentrations for any biologics and the humoral immune response to SARS-CoV-2 vaccines were demonstrated. However, TNFi in combination with thiopurines were associated with an attenuated serologic response, and the serologic response in general was significantly reduced in CD compared to UC patients. Our results indicate that SARS-CoV-2 vaccines can be provided without consideration to the timing of biologic doses in IBD patients and will aid decision-making regarding re-vaccinations and tailoring of medication in order to keep vulnerable IBD patients protected against serious SARSCoV-2 infection.