ABSTRACT
Background: The Centers for Disease Control and Prevention recommends an additional dose (AddDose) of COVID-19 vaccine for moderately/severely immunosuppressed individuals following an initial vaccine series. The American College of Rheumatology suggests that patients interrupt use (hold) certain DMARDs around the time of COVID-19 vaccination to improve immunogenicity. Whether holding DMARDs around an AddDose of COVID-19 vaccine affects RA disease activity or affects frequencies of lymphocyte populations that may be associated with RA disease activity remains unknown. Objectives: To test whether RA disease activity and frequencies of lymphocyte populations change pre-vs. post-AddDose of COVID-19 vaccine, overall and stratifed by holding vs. continuation of DMARDs around the AddDose. Methods: Prospective observational cohort study of patients with RA who had completed an initial COVID-19 vaccine series (2 doses of mRNA vaccine or 1 dose of adenovirus vector vaccine). Subjects enrolled July-November 2021, prior to receiving an AddDose. Subjects held or continued DMARDs around the AddDose based on discussion with their rheumatologist and/or personal decision-making. RA disease activity was assessed weekly using the validated patient-reported RA Disease Activity Index-5 (RADAI-5) from enrollment through 4 weeks post-AddDose. We compared mean RADAI-5 pre-vs. post-AddDose using generalized estimating equations to account for correlated data among individual subjects. We aimed to enroll 60 subjects to achieve 91% power to detect a 15% non-inferiority margin in mean RADAI-5 post-vs. pre-AddDose. A subset of subjects with seropositive RA provided blood for fow cytometry at enrollment and week 4 post-AddDose. Frequencies of lymphocyte populations (T peripheral helper [Tph] cells, T follicular helper [Tfh] cells, age-associated B cells [ABC], and plasmablasts) were compared pre-vs. post-AddDose using Wilcoxon paired tests with Bonferroni correction. Results: Among 71 subjects, mean age was 62 (SD 12) years, 85% were female, and 87% had seropositive RA. Methotrexate (42%) and TNF inhibitors (38%) were the most common DMARDs;21% were taking prednisone. One subject reported COVID-19 infection prior to the AddDose. The mean RADAI-5 was 3.20 (SD 0.23) pre-AddDose compared to 3.25 (SD 0.23) after (difference of 1.6%, p=0.51). Figure 1 displays mean RADAI-5 in 35 (49%) subjects that held at least 1 DMARD and 36 (51%) subjects that continued all DMARDs around the AddDose. Mean change in RADAI-5 between pre-vs. post-AddDose did not signifcantly differ based on whether subjects held vs. continued DMARDs (p for interaction = 0.16). Frequencies of Tph, Tfh, ABC, and plasmablast populations did not signifcantly differ between the pre-and post-AddDose timepoints in subjects that held at least 1 DMARD (n=16) or subjects that continued all DMARD (n=11) (Figure 1). Conclusion: RA disease activity, measured weekly with a validated patient-reported outcome, is stable around the time of an AddDose of COVID-19 vaccine. Lymphocyte subsets of interest in RA were also similar before and after the AddDose, supporting the observation of stable patient-reported RA disease activity. Holding DMARDs was not associated with greater RA disease activity following the AddDose.