Session: (1264–1307) RA – Diagnosis, Manifestations, and Outcomes Poster II
1272: Immunomodulators and Risk for Breakthrough COVID-19 After a Third SARS-CoV-2 mRNA Vaccine Among Patients with Rheumatoid Arthritis: A Cohort Study
Brigham and Women's Hospital Cambridge, MA, United States
Disclosure information not submitted.
Abigail Schiff1, Xiaosong Wang1, Naomi Patel2, Yumeko Kawano1, Jennifer Hanberg3, Emily Kowalski1, Claire Cook2, Kathleen Vanni1, Grace Qian1, Katarina Bade4, Alene Saavedra1, Shruthi Srivatsan2, Zachary Williams2, Rathnam Venkat1, Zachary Wallace5 and Jeffrey Sparks6, 1Brigham and Women's Hospital, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Massachusetts General Hospital, Brigham and Women's Hospital, Boston, MA, 4Brigham and Women's Hospital, Boston, MA, 5Massachusetts General Hospital, Newton, MA, 6Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
Background/Purpose: In August 2021, the CDC recommended a third SARS-CoV-2 mRNA vaccine dose to complete the initial vaccine series for immunosuppressed patients who had previously received 2 mRNA doses. Despite this, some rheumatoid arthritis (RA) patients may remain at increased risk for breakthrough COVID-19 infection, due to use of immunomodulators which lead to blunted immune responses to vaccination and infection. Identifying patients at highest risk for breakthrough infection despite 3 vaccines can prioritize resources for prevention. Therefore, we investigated the risk of breakthrough COVID-19 among RA patients with at least 3 vaccine doses using disease-modifying antirheumatic drugs (DMARDs), especially TNF inhibitors (TNFi) and CD20 inhibitors (CD20i), during the Omicron wave.
Methods: We performed a retrospective cohort study investigating DMARDs and risk for breakthrough COVID-19 among RA patients who had received 3 mRNA vaccines at a large health care system. A previously validated algorithm was used to identify RA patients using a combination of diagnosis codes and DMARD/glucocorticoid prescription (PPV 90%). COVID-19 was identified systematically from positive PCR tests or patient reports to the hospital/clinic of home rapid antigen tests. Patients were followed from the date of 3rd vaccine (index date) until breakthrough COVID-19, non-COVID death, or end of follow-up (January 18, 2023). A previously defined hierarchical algorithm was used to categorize DMARD exposures. Covariates included demographics, lifestyle, comorbidities, and prior COVID-19. We used Cox proportional hazards models to estimate the risk of COVID-19 among different DMARD users. We then used propensity scores and overlap-weighting to further account for confounding when comparing the risk among users of CD20i vs. TNFi.
Results: We identified 5781 patients with RA who used DMARDs/glucocorticoids and received 3 mRNA vaccine doses (78.8% female, mean age 64.2 years). During mean follow up of 12.8 months, 1173 (20.2%) had a SARS-CoV-2 infection (incidence rate 15.7 per 1000 person-months) (Table 1). Users of CD20i were more likely than TNFi users to have COVID-19 after the index date (adjusted HR 1.74, 95%CI 1.30-2.33), as were users of steroid monotherapy (adjusted HR 1.47, 95%CI 1.09-1.98) (Figure 1). After using propensity scores for overlap weighting to account for baseline differences, CD20i users remained at higher risk for COVID-19 than TNFi users (HR 1.62, 95%CI 1.02-2.56; Figure 2). In a sensitivity analysis excluding patients with cancer or interstitial lung disease, the findings were similar.
Conclusion: In this RA-specific study evaluating the impact of DMARD use on the risk of COVID-19 during the Omicron phase of the pandemic, we identified CD20i and steroid monotherapy use as risk factors for breakthrough COVID-19. This contemporary study highlights the excess risk associated with glucocorticoid monotherapy or CD20 inhibitor use for RA treatment and identifies important subgroups for counseling and additional risk mitigation strategies.
Table 1. Baseline demographic and clinical characteristics at date of 3rd mRNA vaccine receipt among patients with rheumatoid arthritis.
Figure 1. Cumulative incidence and hazard ratio for breakthrough COVID-19 by immunomodulator use at 3rd COVID mRNA vaccine dose.
Figure 2. Propensity-score weighted cumulative incidence of COVID-19 after 3rd mRNA vaccine, comparing CD20 inhibitor users vs. TNF inhibitor users.
A. Schiff: None; X. Wang: None; N. Patel: Arrivo Bio, 2, Chronius Health, 2, FVC Health, 2; Y. Kawano: None; J. Hanberg: None; E. Kowalski: None; C. Cook: None; K. Vanni: None; G. Qian: None; K. Bade: None; A. Saavedra: None; S. Srivatsan: None; Z. Williams: None; R. Venkat: None; Z. Wallace: BioCryst, 2, Bristol-Myers Squibb(BMS), 5, Horizon, 1, 2, 5, MedPace, 2, Novartis, 1, PPD, 2, Sanofi, 1, 5, Shionogi, 1, Visterra, 1, 2, Zenas, 1, 2; J. Sparks: AbbVie, 2, Amgen, 2, Boehringer Ingelheim, 2, Bristol-Myers Squibb, 2, 5, Gilead, 2, Inova Diagnostics, 2, Janssen, 2, Optum, 2, Pfizer, 2, ReCor, 2.
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