OP0192 SEROLOGICAL RESPONSE AND SAFETY OF A THREE-DOSE SARS-CoV-2 VACCINATION STRATEGY IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY DISEASES ON IMMUNOSUPPRESSIVE THERAPY

Abstract

Background: Patients with immune-mediated infammatory diseases (IMIDs) on immunosuppressive therapy have an inadequate serologic response following two-dose SARS-CoV-2 vaccination, and a standard vaccination strategy of three doses for this patient group is currently under implementation in several countries. However, the serological response and safety of this strategy has not been evaluated. Objective(s): To assess serological response and safety of a three-dose vaccination strategy in IMID patients on immunosuppressive therapy as compared to standard two-dose vaccination of healthy controls. Method(s): The prospective observational Nor-vaC study (NCT04798625) enrolled adult patients on immunosuppressive therapy for infammatory joint-and bowel diseases. Healthy controls were health care workers from participating hospitals. All participants received standard vaccines according to the national vaccination program with three doses in patients and two doses in controls. The third dose was offered to IMID patients >4 weeks after the second dose. Analyses of antibodies binding the receptor-binding domain of the SARS-CoV-2 Spike protein were performed prior to, and 2-4 weeks after the second and third vaccine doses. Levels were compared across groups by Mann-Whitney U tests and multi-variate linear regression was used to identify predictors of response. Result(s): Overall, 961 patients (315 rheumatoid arthritis, 156 spondyloarthritis, 171 psoriatic arthritis, 132 ulcerative colitis and182 Crohn's disease) (median age 54 years [IQR 43-64]; 56 % women) and 227 controls (median age 44 years [IQR 32-55]; 83 % women) were included in the present analyses. TNFi mon-otherapy was used by 399 patients, 229 used TNFi in combination with other immunomodulators, 189 methotrexate monotherapy, 39 vedolizumab, 32 JAKi and 73 patients used other drugs. Patients on rituximab were not included. Patients were vaccinated with Pfzer BNT162b2 (54% patients, 14% controls), Moderna mRNA-1273 (16% patients, 40% controls) or a combination of vaccines (30% patients, 46% controls). Patients received the third vaccine dose a median of 120 (IQR 102-143) days after the second dose. After two doses, median antiSpike antibody levels were signifcantly lower in patients (861 BAU/ml (IQR 418-4275) than controls (6318 BAU/ml (IQR 2468-9857)), p<0.001 (Figure 1). Following the third dose, patients achieved antibody levels comparable to the two-dose vaccinated controls (median 5480 BAU/ml (IQR 1081-12069), p=0.28) (Figure 1). In the patients anti-Spike antibody levels increased by a median of 2685 BAU/ml (IQR 265-9129) from the second to the third dose. Main factors associated with increased antibody level after the third dose were younger age (beta-87.7 (p=0.002)), and vaccine status (mRNA-1273 vaccine (beta 5549 (p<0.001)) or a combination of vaccines (beta 4367.3 (p<0.001)). Adverse events were reported by 438 (48%) of patients after the third dose as compared to 471 (54%) after the second dose and 193 (78 %) of controls. Disease fares were reported by 42 (5%) and 69 (8%) patients after the second and third dose, respectively. Conclusion(s): This study suggests that a third vaccine dose for immunosup-pressed patients closes the gap in serological response between patients and the healthy population. Antibody levels following the three-dose regimen in IMID patients were comparable to healthy controls vaccinated twice, and no new safety issues emerged. This fnding was consistent across all diagnoses and treatment groups, supporting the implementation of a three-dose vaccine regimen as standard in the IMID population.