COVID-19 Outcomes Among Users of CD20 Inhibitors for Immune-Mediated Diseases: A Comparative Cohort Study

Abstract

Objective: Patients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes due to impaired humoral immunity, but differences versus the general population are unknown. Methods: We identified patients with immune-mediated diseases who received CD20 inhibitors within one year prior to the index date of PCR-confirmed COVID-19 between January 31, 2020, and January 31, 2021. Comparators with COVID-19 were matched up to 5:1 by age, sex, and PCR date. Hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in CD20 inhibitor users versus comparators were estimated using Cox regression. Results: We identified 114 cases with COVID-19 who had received CD20 inhibitors for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). CD20 inhibitor-treated cases had higher mortality (aHR 2.16; 95% CI: 1.03 to 4.54) than matched comparators. Risks of hospitalization (aHR 0.88; 95% CI: 0.62 to 1.26) and mechanical ventilation (aHR 0.82; 95% CI: 0.36 to 1.87) were similar. Similar trends were seen in analyses according to type of indication (e.g., rheumatic or neurologic disease) and duration of CD20 inhibitor use (<1 or ≥1 year), and after excluding patients with interstitial lung disease, cancer, and those on glucocorticoids prior to COVID-19 diagnosis. Conclusions: Patients who received CD20 inhibitors for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in CD20 inhibitor users during the ongoing pandemic.

COVID-19 in Patients with Hematologic Malignancies: Clinical Manifestations, Persistence, and Immune Response

“…Third, patients receiving anti-CD20 therapy (aCD20), i.e., obinutuzumab or rituximab, are at increased risk for COVID-19 mortality, prolonged infection, protracted viral shedding, and decreased protection as a result of vaccination [61]. While increased mortality was not evident in all cohorts [36], other [35, 120], well-designed (albeit retrospective) studies showed increased mortality risk (HR 2.16, 95% CI [1.03–4.54]) [120]. Perhaps more importantly, aCD20 deeply impairs the immune response to COVID-19 vaccination.…”

Breakthrough SARS-CoV-2 infections in immune mediated disease patients undergoing B cell depleting therapy

“…While patients with IMIDs on BCDTs have been recognized to be vulnerable to severe COVID-19 infections, 3,4,6,7 relatively scant data exist regarding their risks for and outcomes of breakthrough infections 2,18 . The current cohort of breakthrough patients consisted of nearly equal numbers of patients with rheumatic and neuro-inflammatory disease and most (91.9%) were either fully vaccinated or boosted, with only 6 (8.1%) with incomplete vaccination.…”

“…While there is great heterogeneity in the capacity of specific immunosuppressive agents to limit the integrated immune response to both natural infection as well as vaccines, of particular concern is the class of B cell depleting therapies (BCDTs) widely used to treat an array of IMIDs. Before the introduction of vaccines, treatment of both rheumatic and neurologic IMIDs with such BCDTs was associated with more severe COVID-19 [3][4][5][6][7][8][9] . Furthermore, numerous studies have documented the capacity for BCDTs such as rituximab and ocrelizumab to profoundly impair humoral response to numerous vaccines including SARS-CoV-2 [10][11][12][13] .…”

Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C)

“…As the pandemic has progressed, a higher risk of incident COVID-19 infection or worse outcomes in certain immunocompromised subpopulations, such as those with rheumatoid arthritis (RA) [ 1 , 2 ] has been described. This is potentially related not only to their underlying disease but also due to the use of immunosuppressive medications used to treat RA [ 3 , 4 ]. Specifically, some studies have raised concerns regarding rituximab (RTX) exposure being associated with worse COVID-19 outcome [3] , [4] , [5] , [6] .…”

“…This is potentially related not only to their underlying disease but also due to the use of immunosuppressive medications used to treat RA [ 3 , 4 ]. Specifically, some studies have raised concerns regarding rituximab (RTX) exposure being associated with worse COVID-19 outcome [3] , [4] , [5] , [6] . For example, Sparks et al, using the data from the global rheumatology alliance (GRA) that contained physician-reported survey data, found that people with RA who were treated with RTX or JAK inhibitor had worse COVID-19 severity (defined as hospitalization/death) than those on tumor necrosis factor inhibitors (TNFi) [5] .…”