COVID-19 VaccinE Response in Rheumatology Patients

There is an urgent need to determine the immunogenicity and safety of COVID-19 vaccines in people living with rheumatic disease on immunomodulatory therapies. Given the experience with influenza, pneumococcal, shingles, and other vaccinations in rheumatic disease populations, it is clear that disease modifying therapies (DMARDs) and the immunomodulatory therapies used to treat immune-mediated inflammatory diseases have the capacity to blunt immune responses to vaccinations. A number of mostly small studies have examined the optimal management of DMARDs with regard to the timing of vaccination in order to maximize the immunogenicity of various vaccines, with immunogenicity serving as a lab-based proxy for clinical effectiveness. As various development programs near completion with regard to a vaccine for SARS-CoV-2 virus, it will be imperative to understand how best to vaccinate immunosuppressed patients, and in particular, to optimize vaccine response resulting from a supplemental (booster) dose in those patients using immunomodulatory biologic and targeted small molecule therapies. In concert with the American College of Rheumatology's (ACR) task force focused on developing COVID-19 vaccination guidance, the proposed real-world study will address major knowledge gaps that exist with the SARS-CoV-2 vaccination in rheumatic disease patients who have not been included in vaccine studies. Currently, the ACR task force for COVID-19 vaccination guidance recommends that patients temporarily (1-2 weeks) stop one of their medications for their autoimmune inflammatory disease. However, it is not known if stopping medications may increase risk of flares in their autoimmune condition. If these occur, they are expected to occur within 2-4 weeks of treatment interruption.

Approximately 1000 patients will be studied to address these questions about the vaccine response following supplemental (booster) dosing associated with the use of upadacitinib, baricitinib, abatacept, canakinumab, secukinumab, ixekizumab, tofacitinib, TNFi, guselkumab (conditional on resource availability), and ustekinumab (conditional on resource availability). Participants will be randomized to hold these treatments for two weeks, or to continue their medication without interruption.

Study Objectives and Hypotheses

To conduct a large, randomized controlled trial to evaluate SARS-CoV-2 vaccine supplemental dose response in a large population of patients with autoimmune conditions, designed to meet three specific objectives and aims:

1. Specific Aim 1: Evaluate the immunogenicity of SARS-CoV-2 vaccination in patients with autoimmune conditions, randomizing patients to briefly interrupt (i.e., hold for 2 weeks) versus continue various immunomodulatory therapies at the time that they receive a supplemental (i.e., booster) mRNA vaccine dose.