IMPACT OF IMMUNOSUPPRESSIVE THERAPIES ON ANTIBODY DECAY FOLLOWING MRNA VACCINATION TO SARS-COV-2 IN A PROSPECTIVE COHORT OF PATIENTS WITH CHRONIC INFLAMMATORY DISEASES

ABSTRACT

Background: Waning levels of anti-SARS-CoV-2 Spike (S) antibodies, particularly neutralizing, are associated with the risk of breakthrough infections. The impact of immunosuppression on antibody decay kinetics is unclear. We have previously reported a strong correlation between total anti-S antibodies and neutralization titers. Here, we report the decay kinetics in anti-S IgG antibodies across various immunosuppressive medications used in patients with CID. Methods: We recruited a volunteer sample of adults with confirmed CID eligible for SARS-CoV-2 vaccination in a prospective observational cohort study at two United States CID referral centers. All study participants received two doses of mRNA vaccine to SARSCoV- 2. To assess the durability of immunogenicity, anti-S IgG were measured at 7 (visit 3), 90 (visit 5), and 120 (visit 6) days after the 2nd dose of mRNA vaccine. The impact of various medications was assessed in repeated measures mixed model with the patient as a random effect, adjusting for gender and age, and using the group of patients on sulfasalazine, NSAIDs, or on no medications as a reference, using STATA. The half-life of anti-S IgG for a 50 percent reduction in titers at visit 3 was calculated for each medication class. Results: A total of 316 CID patients were recruited of which 148 (46.8%) had inflammatory bowel disease (IBD). Durability was assessed in 495 samples obtained in 293 patients. The arithmetic mean of anti-S IgG antibodies for each medication class at visits 3, 5, and 6 is shown in Figure 1. Overall, a 2-fold reduction in titers was observed from 7 to 90 days and 90 to 120 days (Table 1). The strongest decline was observed among patients on B cell depleting/ modulating therapies followed by those on combinations of biologics and/or small molecules and antimetabolites (methotrexate, leflunomide, thiopurines, mycophenolate mofetil, and teriflunomide). There was modest decline seen with TNFi (half-life 430.5 days, -2.15, 95% CI - 4.31 to - 1.07, p = 0.03). There was also a modest, but not significant, decline seen with Janus Kinase inhibitor (JAKi). No decline was seen with anti-IL-23 or anti-integrin medication classes. Conclusions: Antibody decay in patients with CID is not observed in patients on anti-integrins or anti-IL-23 while it is seen among patients on TNFi, JAKi, antimetabolites, and combinations of biologics and/or small molecules. Our data and those from other cohorts may be used to prioritize medication classes for boosting immunogenicity with additional doses of vaccination against SARS-CoV-2. Collection of antibody titers after booster doses is currently ongoing.(Table Presented) (Figure Presented) Figure 1 Durability of anti-spike IgG antibodies after vaccination against SARS-CoV-2 in patients with Chronic Inflammatory Disease