Patients on B-cell depleting therapies at risk for breakthrough COVID-19, severe outcomes
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Patients with immune-mediated inflammatory diseases receiving B-cell depleting therapies are at risk for COVID-19 regardless of vaccine status, but outpatient use of monoclonal antibodies improves clinical outcomes, according to data.
“The deployment of vaccines to both prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as limit the severity of coronavirus disease 2019 (COVID-19) has proven efficacious for the general population,” Cassandra Calabrese, DO, of the Cleveland Clinic, and colleagues wrote in Arthritis & Rheumatology. “However, data on patients with underlying immunocompromising conditions, including those with immune-mediated inflammatory diseases (IMIDs), suggest both an increased likelihood for developing breakthrough infections and for experiencing more severe outcomes despite full vaccination status.”
To investigate the presence of COVID-19, and its outcomes, among patients with immune-mediated inflammatory diseases (IMIDs) receiving B-cell depleting therapy, Calabrese and colleagues conducted a retrospective cohort analysis. They searched pharmacy records from the Cleveland Clinic to identify patients receiving B-cell depleting therapy in 2020 before receiving any COVID-19 vaccinations. The therapies in question included rituximab (Rituxan, Genentech), ocrelizumab (Ocrevus, Genentech) and ofatumumab (Kesimpta, Novartis).
The researchers then cross-referenced those records to identify which patients received at least one dose of vaccine and subsequently experienced a breakthrough infection. The authors only included infections that were confirmed by a positive PCR or rapid test. Demographic information including age, gender and race were extracted. Additionally, information regarding weight, comorbidities, immunosuppressive medications, prednisone use, timing and duration of B-cell depleting therapy, vaccine type, monoclonal antibody use and clinical outcomes were collected.
The primary outcome was disease severity according to the eight-point NIH COVID-19 ordinal scale. Patients were classified as having had mild COVID-19 with a score of one to three, or severe with a score of four to eight.
The study included 1696 patients with IMIDs receiving B-cell depleting therapy, of which 74 developed breakthrough infections. The authors categorized the overall outcomes of these patients as “severe,” with 29 (39.2%) being hospitalized, 11 (14.9%) requiring critical care and six (8.1%) dying. A total of 21 patients received monoclonal antibody therapy. Among these patients, one required hospitalization and none died. Of the 1,437 unvaccinated patients with IMIDs on B-cell depleting therapy, 57 were diagnosed with COVID-19, with 28 (49.1%) requiring hospitalization and seven (12.3%) dying.
“In terms of practical implications, our study should serve to highlight the plight of this important segment of the immunocompromised patient population who are likely to face ongoing and formidable risks despite aggressive vaccination if, as many observers predict, an ensuing endemic phase of the pandemic lies ahead with future variants of unknown pathogenicity,” Calabrese and colleagues wrote. “Enhanced education of both patients and the providers who care for them to increase their awareness and utilization of current and future outpatient therapies is urgently needed.”
Perspective
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In this retrospective cohort study, Calabrese and colleagues evaluated 74 patients with immune-mediated diseases receiving B-cell depletion therapy who developed breakthrough COVID-19 infection, and found that 35% were hospitalized, 15% required critical care and 8% died. They found a very low risk of hospitalization and no deaths among those who received monoclonal antibody therapy.
These results demonstrate that patients receiving B-cell depletion remain at higher risk for severe outcomes of COVID-19 breakthrough infection than the general population. They also evaluated risks for severe outcomes in a comparator group of unvaccinated patients receiving B-cell depletion and found numerically higher risks for hospitalization (49%) and death (12%) than in the vaccinated group. Those with 2 or more comorbidities were also at higher risk for poor outcome.
Ongoing efforts to target this population with both prophylactic and therapeutic measures remain important given the risk for severe outcomes despite vaccination. Further studies evaluating the efficacy of pre-exposure prophylaxis with tixagevimab and cilgavimab (Evusheld, AstraZeneca) and other evolving therapies in this population are needed as prophylactic and therapeutic measures evolve.
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