Factors associated with COVID-19 breakthrough infection among vaccinated patients with rheumatic diseases: A cohort study

Abstract

Objective: Rheumatic disease patients on certain immunomodulators are at increased risk of impaired humoral response to SARS-CoV-2 vaccines. We aimed to identify factors associated with breakthrough infection among patients with rheumatic diseases.

Methods: We identified patients with rheumatic diseases being treated with immunomodulators in a large healthcare system who received at least two doses of either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) vaccines or one dose of the Johnson & Johnson-Janssen (J&J) vaccine. We followed patients until SARS-CoV-2 infection, death, or December 15, 2021, when the Omicron variant became dominant in our region. We estimated the association of baseline characteristics with the risk of breakthrough infection using multivariable Cox regression.

Results: We analyzed 11,468 patients (75% female, mean age 60 years). Compared to antimalarial monotherapy, multiple immunomodulators were associated with higher risk of infection: anti-CD20 monoclonal antibodies (aHR 5.20, 95% CI: 2.85, 9.48), CTLA-4 Ig (aHR 3.52, 95% CI: 1.90, 6.51), mycophenolate (aHR 2.31, 95% CI: 1.25, 4.27), IL-6 inhibitors (aHR 2.15, 95% CI: 1.09, 4.24), JAK inhibitors (aHR 2.02, 95% CI: 1.01, 4.06), and TNF inhibitors (aHR 1.70, 95% CI: 1.09, 2.66). mRNA-1273 recipients had a lower risk of breakthrough infection compared to BNT162b2 recipients (aHR 0.66, 95% CI: 0.50, 0.86). There was no association of sex, body mass index, smoking status, race, or ethnicity with risk of breakthrough infection.

Conclusion: Among patients with rheumatic diseases, multiple immunomodulators were associated with increased risk of breakthrough infection. These results highlight the need for additional mitigation strategies in this vulnerable population.

Fig. 1

Identification of vaccinated rheumatic disease patients within the Mass General Brigham healthcare system, MGB, Mass General Brigham healthcare system.

Fig. 2

Cumulative probability of COVID-19 breakthrough infection after vaccination, by immunomodulatory medication and vaccine type Legend: CTLA-4 Ig, cytotoxic T-lymphocyte associated protein 4 immunoglobulin; DMARD, disease-modifying antirheumatic drug; IL, interleukin; JAK, Janus kinase; TNF, tumor necrosis factor Cumulative probability of breakthrough infection after the date of initial vaccine series (two doses of either Moderna or Pfizer-BioNTech or one dose of Johnson & Johnson-Janssen) using the multivariable model adjusted for age, sex, smoking, Charlson Comorbidity Index, and vaccine type. A. Cumulative probability in those receiving antimalarial monotherapy, JAK inhibitors, IL-6 inhibitors, CTLA-4 Ig, or anti-CD20 monoclonal antibodies. B. Cumulative probability in those who received the Pfizer-BioNTech, Moderna, or Johnson & Johnson-Janssen vaccine.