The US Centers for Disease Control and Prevention (CDC) recommends three SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine doses, rather than two, to complete the initial vaccine series for immunosuppressed patients. However, they may remain at risk for breakthrough COVID-19 due to immunomodulators that blunt vaccine responses.1 Identifying patients at highest risk for breakthrough COVID-19 can prioritise resources for prevention. Therefore, we investigated the risk of breakthrough COVID-19 among fully vaccinated patients with rheumatoid arthritis (RA) using disease-modifying antirheumatic drugs (DMARDs) and/or glucocorticoids, hypothesising that CD20 inhibitor (CD20i) users would have higher breakthrough COVID-19 risk than tumour necrosis factor inhibitor (TNFi) users.

We performed a retrospective cohort study investigating immunomodulators and breakthrough COVID-19 risk among patients with RA who received three mRNA vaccines at Mass General Brigham, a multicentre healthcare system in Boston, Massachusetts, USA. A previously validated algorithm was used to identify patients with RA (postive predictive value 90%).2 COVID-19 was identified from positive PCR tests or patient reports to the hospital/clinic of home rapid antigen tests.2 Patients were followed from the date of the third vaccine (index date) until breakthrough COVID-19 (occurring ≥14 days after index date), non-COVID-19 death or end of follow-up (18 January 2023). A previously defined hierarchy categorised immunomodulator medications at index date into mutually exclusive groups.2 Covariates included demographics, lifestyle, calendar time and clinical factors. We used multivariable Cox regression models to estimate HRs for breakthrough COVID-19 by immunomodulator class. We then used propensity score (PS) overlap-weighting to further account for confounding and compare users of CD20i versus TNFi for breakthrough COVID-19.

We analysed 5781 patients with RA …