Antibody response to the COVID-19 ChAdOx1nCov-19 and BNT162b vaccines after temporary suspension of DMARD therapy in immune-mediated inflammatory disease: an extension study (RESCUE 2).

The persistence of immunogenicity in patients with immune-mediated inflammatory diseases (IMID) on disease-modifying antirheumatic therapy (DMARD) has been less well studied. This extension study evaluates the SARS-CoV2 antibody decay kinetics 6 months following two doses of ChAdO1nCov-19 (AZ) and BNT162b (Pfizer) and subsequent response following an mRNA booster. RESULTS: 175 participants were included. Six months after initial AZ vaccination, 87.5%, 85.4% and 79.2% (p=0.756) in the withhold, continue and control groups remained seropositive compared with 91.4%, 100% and 100% (p=0.226), respectively, in the Pfizer group. Both vaccine groups developed robust humoral immune responses following a booster with seroconversion rates being 100% for all three intervention categories. The mean SARS-CoV-2 antibody levels were significantly lower in the targeted synthetic DMARD (tsDMARD) group that continued therapy compared with the control (2.2 vs 4.8 U/mL, p=0.010). The mean time interval until loss of protective antibodies in the IMID group was 61 days for the AZ and 137.5 days for the Pfizer vaccine. Within each DMARD class the interval until loss of protective antibody titres in the csDMARD, bDMARD and tsDMARD groups were 68.3, 71.8 and 64.0 days in the AZ group and 185.5, 137.5 and 116.0 days in the Pfizer group, respectively. CONCLUSION: Antibody persistence was longer in the Pfizer group due to a higher peak antibody level following second vaccination with levels of protection in IMID on DMARD therapy similar to controls except in those on tsDMARDs where it was lower. A third mRNA vaccine booster can restore immunity in all groups.

Antibody response to the COVID-19 ChAdOx1nCov-19 and BNT162b2 vaccines in the immunosuppressed (RESCUE)

Background: Immunocompromised patients are inherently vulnerable to severe outcomes to vaccine preventable infections compared to the general population. This study aims to investigate the impact of immunosuppression on response to the ChAdOx1nCov-19 and BNT162b2 vaccines to better inform vaccination efforts in this cohort. Methods: A three-armed randomised controlled trial was performed. Patients with autoimmune disorders on immunosuppressive therapies and healthy controls were recruited from two sites. Participants receiving immunosuppression were randomly assigned to either withhold or continue treatment contemporaneous to vaccine administration. Serum SARS-Cov2 immunoglobulin assays were performed at baseline and, 4-weeks following first and second vaccine doses. Between group comparisons were performed to examine differences in vaccine seroconversion and immunogenicity. Results: A total of, 253 participants of median age, 55 years (IQR:, 45.5-64) including, 193 patients receiving immunosuppression and, 60 healthy controls were studied. Immunosuppressed patients were randomly allocated to continue (n=105) or withhold (n=88) treatment. Of those receiving immunosuppression, 27.08%, 40.63% and, 32.29% of patients were exposed to cDMARDs, bDMARDs and tsDMARDs respectively while rates of BNT162b (Pfizer) vaccination were, 52.33%, 60.67% and, 48.33% among the continue, withhold, and control groups respectively. Post-first dose vaccination seroconversion rates were highest among healthy controls (90%) and patients who temporarily withheld immunosuppressants (76.32%) compared to patients continuing treatment (48.24%) p=0.000. Postsecond dose vaccination seroconversion rates were, 100% in both the control and withhold groups and, 86.75% in the continuation (p=0.001). Mean quantitative serum SARS-CoV-2 IgG titres were, 8.58 U/ml, 5.11 U/ml and, 3.29 U/ml (p=0.0001) between the controls, withhold and continue groups respectively following first vaccination. While post-second vaccination mean serum IgG titres were, 96.31 U/ml, 91.86 U/ml, and, 49.73 U/ml (p=0.0066) between these groups. Conclusion: COVID-19 vaccine response in terms of seroconversion and the level of antibody production was highest among healthy controls compared with patients with autoimmune diseases receiving immunosuppression. Temporary cessation of immunosuppressant therapy, contemporaneous to COVID19 vaccination appears to improve vaccine response in this cohort. (Figure Presented).