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 stratified 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 flow 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 significantly differ based on whether subjects held vs. continued DMARDs (p for interaction = 0.16). Frequencies of Tph, Tfh, ABC, and plasmablast populations did not significantly 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.

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Disclosure of Interests Sara Tedeschi Consultant of: NGM Biopharmaceuticals: payment to Dr. Tedeschi, Grant/research support from: Moderna: research support to institution, Jacklyn Stratton: None declared, Jack Ellrodt: None declared, Mary Grace Whelan: None declared, Keigo Hayashi: None declared, Kazuki Yoshida Consultant of: OM1, Inc: consulting fees paid to Dr. Yoshida, Lin Chen: None declared, Ifeoluwakiisi Adejoorin: None declared, Kathryne E. Marks: None declared, A. Helena Jonsson Grant/research support from: Moderna: research support to institution

Amgen: payment to institution for unrelated project, Deepak Rao Speakers bureau: Merck: honoraria lecture paid to Dr. Rao, Consultant of: Janssen: consulting fees paid to Dr. Rao

Bristol Myers Squibb: participation on scientific advisory board with compensation paid to Dr. Rao, Grant/research support from: Moderna: research funding paid to institution

Janssen: research funding paid to institution

Merck: research funding paid to institution, Daniel Solomon Grant/research support from: Moderna: payment made to institution

Amgen: payment to institution

Abbvie: payment to institution

CorEvitas: payment to institution