Serological Responses to SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease Are Impaired for Those on Anti-TNF and Immunomodulator Combination Therapy

Introduction: Anti-tumor necrosis factor (TNF) reduces the serological responses (SR) to SARS-CoV-2 vaccination and impairs SR durability within individuals with IBD.1-3 Additional doses of SARS-CoV-2 vaccination effectively increase antibody titers in patients treated with anti-TNF agents, responses are still lower compared to healthy controls.4 5 Data comparing serological responses between anti-TNF monotherapy and combination therapy are lacking. This study aims to compare serological responses from SARS-CoV-2 vaccination between IBD patients treated with anti-TNF monotherapy or combined with an immunomodulator. Methods: Adults with IBD, at least two doses of a SARS-CoV-2 vaccine, with anti-TNF monotherapy (anti-TNF alone) or combination therapy (anti-TNF in addition to methotrexate or azathioprine) were recruited through the STOP COVID-19 in IBD cohort.5 Serum samples were drawn for assessment of IgG antibodies to the spike protein of SARS-CoV-2 (anti-S) using the Abbott Architect SARS-CoV-2 IgG II Quant assay following 1–8 weeks after 1st dose vaccination, and both 1–8 weeks and 8+ weeks after 2nd, 3rd, and 4th dose vaccination. Demographic and medication status information was collected through chart review. SR was defined as IgG levels of ≥50 AU/mL; positive SR rates were compared between medication groups using two-sample proportion tests. Anti-S concentrations were reported as geometric mean titres (GMT) with 95% confidence intervals and were compared between medication groups using Mann Whitney-U tests. Results: 207 patients on anti-TNF monotherapy and 68 on combination therapy were recruited. Anti-S titres were significantly decreased for individuals on combination therapy compared to anti-TNF monotherapy 1–8 weeks after 1st dose vaccination, and both 1–8 weeks and 8+ weeks after 2nd dose vaccination. No significant differences in GMTs were determined between anti-TNF monotherapy and combination therapy groups following all timepoints after additional dose vaccination (Table 1, Figure 1). Conclusion: IBD patients treated with combination therapy develop a significantly reduced serological response to a two-dose SARS-CoV-2 regimen compared to those with anti-TNF monotherapy. These differences are no longer observed following additional vaccine doses and both medication groups develop robust antibody responses. These findings highlight the importance of additional doses for adequate serological protection within the IBD population and especially for those on anti-TNF combination therapy. Table 1. - Overall patient characteristics, seroconversion, and GMT with associated 95% CIs per vaccine serology timepoint for anti-TNF monotherapy and anti-TNF + IMM combination therapy with associated univariate analyses Characteristic Time point Anti-TNF Monotherapy (n = 207) Anti-TNF + IMM (n = 68) P-value Male sex, n (%) Overall 89 (43.0%) 36 (52.9%) – Mean age (SD) 48.1 (14.8) 45.0 (13.8) – IBD type, n (%) – Crohn’s disease 154 (74.4%) 53 (77.9%) Ulcerative colitis 49 (23.7%) 14 (20.6%) IBD-Unclassified 4 (1.9%) (1.5%) Seroconversion, n/N (%) Post-1st 65/77 (83.1%) 16/32 (50.0%) < 0.001 Post-2nd (1–8 weeks) 114/115 (99.1%) 36/37 (97.3%) 0.395 Post-2nd (8+ weeks) 90/95 (94.7%) 18/22 (81.8%) 0.041 Post-3rd (1–8 weeks) 90/90 (100.0%) 30/30 (100.0%) N/A Post-3rd (8+ weeks) 116/117 (99.2%) 37/37 (100.0%) 0.573 Post-4th (1–8 weeks) 31/31 (100.0%) 11/11 (100.0%) N/A Post-4th (8+ weeks) 24/25 (96.0%) 14/14 (100.0%) 0.448 GMT (95% CI) Post-1st 266 (176, 400) 84 (45, 156) < 0.001 Post-2nd (1–8 weeks) 3185 (2528, 4011) 1102 (728, 1670) < 0.001 Post-2nd (8+ weeks) 612 (437, 858) 289 (139, 599) 0.045 Post-3rd (1–8 weeks) 9013 (7166, 11335) 5664 (3493, 9185) 0.096 Post-3rd (8+ weeks) 2698 (2006, 3630) 1695 (947, 3034) 0.210 Post-4th (1–8 weeks) 9803 (6911, 13907) 7711 (4071, 14607) 0.393 Post-4th (8+ weeks) 2931 (1597, 5381) 2996 (1455, 6168) 0.861 Figure 1.: Anti-SARS-CoV-2 antibody concentration per vaccine category stratified anti-TNF monotherapy (squares) and anti-TNF combination therapy (triangles). Black circles represent GMTs while narrow black bars represent bounds of 95% CI associated with each GMT. Solid blue line for positive seroconversion (50 AU/mL).