Breakthrough SARS‐CoV‐2 infections in immune mediated disease patients undergoing B cell depleting therapy: A retrospective cohort analysis

OBJECTIVES: Patients with immune mediated inflammatory diseases (IMIDs) receiving B cell depleting therapy (BCDT) are among the most vulnerable to severe COVID‐19 as well as the most likely to respond sub‐optimally to SARS‐CoV‐2 vaccines. However, little is known about the frequency or severity of breakthrough infection in this population. We retrospectively analyzed a large group of vaccinated IMIDs patients undergoing BCDT in order to identify the presence of breakthrough COVID‐19 infections and assess their outcomes. METHODS: In this retrospective cohort study, the pharmacy records and COVID‐19 registry at the Cleveland Clinic were searched using specific ICD‐10 codes to identify IMIDs patients who (1) were treated with BCDT, (2) were vaccinated against SARS‐CoV‐2, and (3) experienced breakthrough infections. Each EMR was reviewed to extract clinical data and outcomes. Univariate and multivariable logistic/proportional‐odds regression models were used to examine the risk factors for severe outcomes. RESULTS: Of 1696 IMIDs patients on BCDT, 74 developed breakthrough COVID‐19 prior to December 16th, 2021. Outcomes were severe with 29(39.2%) hospitalized, 11(14.9%) requiring critical care, and 6(8.1%) deaths. Outpatient anti‐SARS‐CoV‐2 monoclonal antibodies were used to treat 21 with 1 hospitalization and no deaths. A comparator analysis examining 1437 unvaccinated IMIDs patients on BCDT over the same time period identified 57(3.9%) COVID‐19 cases with 28(49.1%) requiring hospitalization including 7(12.3%) deaths. CONCLUSIONS: IMIDs patients on BCDT regardless of vaccine status appear vulnerable to infection with SARS‐CoV‐2 and are frequently associated with severe outcomes. Outpatient use of anti‐SARS‐CoV‐2 monoclonal antibody therapy appeared to be associated with enhanced clinical outcomes.