(BSPOT52) Immunomodulatory treatment and immune responses to COVID-19 booster shots in patients with autoimmune rheumatic diseases: Results from the Covid-19 VaccinE Response in Rheumatology patients (COVER) study

Background: Given an increased risk of COVID-19 in patients with autoimmune conditions, we must understand the immunogenicity and safety of SARS-CoV-2 vaccines in people living with rheumatic disease. We conducted the Covid VaccinE Response (COVER) trial, a multicenter, randomized controlled trial to assess the response to the COVID-19 booster vaccine in rheumatology patients on immunomodulatory therapies.

Objectives: We assessed if patients randomized to hold therapy for 2 weeks after a booster had improved vaccine response compared to those who continued therapy.

Methods: COVER, conducted in the Excellence Network in RheumatoloGY (ENRGY), randomized rheumatoid arthritis (RA) or spondylarthritis (SpA) patients to continue or hold their medication, abatacept (ABA) or tumor necrosis factor inhibitors (TNFi), for 2 weeks following a COVID-19 booster vaccine. LabCorp Cov2Quant IgG™ Spike assay measured levels of anti-Receptor Binding Domain (RBD) IgG antibodies prior to and following the booster. We looked at the mean log-transformed difference pre- and post-booster and used linear regression to compare the change in COVID-19 RBD antibody levels, adjusting for age, sex, BMI, methotrexate (MTX) use, and number of prior vaccine doses.

Results: There were no significant baseline differences in demographics or clinical characteristics in the ABA (n=142) and TNFi (n=121) groups. The groups were 76% female, 92% white, 17% Hispanic, mean (SD) age of 61.1 (13.5) years and mean (SD) BMI of 31.2 (8.2) kg/m2. The ABA group was significantly older than the TNF group: 64.8 (11.7) vs 57.1 (14.3), p< 0.0001. Following the booster, RBD antibody titers increased significantly in ABA (p=0.0029 for holding; p=0.03604 for continuing) and TNF (p < 0.0001 for both arms) patients. Patients who continued ABA had a numerically lower increase in anti-RBD antibody titers compared to those who held for two weeks. However, in linear regression, the mean increase in the holding arm compared to the continuing arm was not significantly different for ABA or TNFi groups in unadjusted analysis or after adjusting for demographic and clinical factors. There was no significant interaction in the effect of holding between the ABA and TNFi groups (interaction p-value = 0.55). Improved vaccine response was associated with higher BMI (β=0.04, p=0.03) in the ABA analysis and no concurrent MTX use (β=0.63, p=0.02) in TNFi.

Conclusions: Patients with RA and SpA receiving ABA and TNFi had a significant increase in antibody response after receiving a COVID-19 booster. Holding TNFi did not improve vaccine response and holding ABA for 2 weeks post-booster showed small, but not statistically significant improvement. Based on these results, briefly interrupting ABA or TNFi at the time of COVID boosting may not be warranted.