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Vaccines

2C-04 - Randomization to Holding versus Continuing (JAKi, IL17) and Autoimmune Patient Responses to COVID-19 Boosters: Results from the Covid-19 VaccinE Response in Rheumatology Patients (COVER) Study

Sunday, August 24, 2025
4:15 PM - 4:30 PM ET
Background: Best practice for the use of immunosuppression to optimize vaccine response remains uncertain. We conducted the Covid VaccinE Response (COVER) trial, a multicenter, randomized controlled platform trial to assess the response to the SARS-CoV-2 booster in rheumatology patients on immunomodulatory therapies.

Objectives: The primary goal was to assess whether randomizing to hold Janus kinase inhibitors (JAKi), interleukin-17 inhibitors (IL-17i), abatacept (ABA), or tumor necrosis factor inhibitors (TNFi) for 2 weeks at the time of COVID-19 booster improved vaccine response compared to continuing therapy.

Methods: COVER enrolled patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) being treated with JAKi/biologics in the Excellence Network in RheumatoloGY (ENRGY), a practice-based research network. Patients, who previously received >2-dose mRNA vaccines, were randomized (1:1) to continue or hold therapy for 2 weeks following a COVID-19 booster. LabCorp Cov2Quant IgG™ anti-Spike assay measured anti-Receptor Binding Domain (RBD) IgG antibodies before and 6 + 2 weeks after the booster. We compared mean log-transformed differences pre- and post-booster and report the geometric mean fold rise (GMFR) by intervention group and therapy. We used linear regression to compare groups for change in COVID-19 RBD antibody levels, adjusting for age, sex, BMI, methotrexate use, steroid use, and time from booster to measurement. Patient-reported flare following booster was compared by intervention group.

Results: Patients on JAKi (n=232) or IL-17i (n=121) were 79% female, 88% white, 29% Hispanic, with mean (SD) age of 59.2 (11.6) years and BMI of 31.8 (7.6) kg/m2. Report of flare following booster was greater among those holding therapy for 2 weeks (JAKI: 34% in hold group vs 9% continue, p< 0.0001; IL-17i: 30% vs 16%, p=0.20). Following vaccine booster dose, RBD antibody titers increased significantly in both JAKi and IL-17i groups (p < 0.0001 for all arms) and all groups showed a GMFR >3. Mean increase in RBD antibodies in the hold vs. continue arm was not significantly different by drug group, before or after adjustment. A decreased effect in change in RBD antibodies was seen for JAKi (β=-0.42, p=0.018) and ABA (β=-0.73, p< 0.001), referent to IL-17i, as well as steroid use (β=-0.31, p=0.041); higher BMI (β=0.015, p=0.039) was associated with greater change in antibody levels.

Conclusions: RA and SpA patients taking JAKi or IL-17i had a significant increase in humoral antibody response after receiving a COVID-19 booster. Holding therapy for 2 weeks did not enhance response compared to continuing therapy. Based on these results and an increase in the frequency of disease flare, interrupting JAKi or IL-17i at the time of COVID-19 boosting does not appear warranted.