Anti-CD20 Monoclonal Antibody Therapy for Immune-mediated Diseases Increases Risk of Death from COVID-19

Patients with immune-mediated inflammatory diseases (IMIDs) who use an anti-CD20 monoclonal antibody (mAb) have greater odds of severe COVID-19 outcomes and death than patients with IMIDs who receive other immunosuppressive or immunomodulatory medications, according to results from multiple disease-specific registries.

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Such research has limitations, including reporting bias and lack of details about mAb use (e.g., indication and duration of exposure). To address these shortcomings, Zachary S. Wallace, MD, MSc, and Naomi J. Patel, MD, physicians in the Rheumatology Unit of the Department of Medicine at Massachusetts General Hospital, Jeffrey A. Sparks, MD, MMSc, of Brigham and Women's Hospital, and colleagues conducted a multicenter study at Mass General Brigham.

Their report in ACR Open Rheumatology confirms an increased risk of death in patients with IMIDs who are treated with anti-CD20 mAbs.

Methods

The researchers made use of the data warehouse for Mass General Brigham, a healthcare system that comprises 14 academic and community hospitals. They identified 114 patients (70% female, mean age 55) who received an anti-CD20 mAb for a non-oncologic and non-transplantation indication within 12 months before being diagnosed with COVID-19.

The most common indication for anti-CD20 mAb use was rheumatic disease (47%), followed by neurologic conditions (38%). 79% of patients received rituximab or a biosimilar, and 23% received ocrelizumab. 42% had received their latest mAb infusion within three months before the COVID-19 diagnosis.

559 individuals drawn from the general population of COVID-19 patients (no IMID, had not received an anti-CD20 mAb) were matched to the other patients on age, sex and date of COVID-19 diagnosis. Race and ethnicity were also similar between groups. COVID-19 diagnoses were made between January 31, 2020, and January 31, 2021.

Primary Analyses

The risk of the primary outcome, death, was 11% in patients treated with anti-CD20 mAbs vs. 4% in the comparator group (adjusted HR, 2.16; 95% CI: 1.03–4.54). No deaths were noted to be related directly to an IMID.

The risks of hospitalization and mechanical ventilation were similar in the two groups. The discrepancy between increased risk of death but no increased ventilator use might be attributable to the incidence of "do not intubate" orders (5% in the IMID group vs. 2% of the comparator group). It's likely the need for mechanical ventilation among patients who received an anti-CD20 mAb was underestimated.

Subgroup and Sensitivity Analyses

The findings were similar when the research team evaluated the following subgroups of patients:

• Those with a rheumatic disease as the indication for anti-CD20 mAb use
• Those with a neurologic disease as the indication
• Short-term users of anti-CD20 mAbs (<1 year)
• Longer-term users of anti-CD20 mAbs (≥1 year)
• Those with recent exposure to an anti-CD20 mAb (within 3 months prior to COVID-19 diagnosis)

Recommendations for Clinicians

Healthcare professionals need to interpret these results cautiously, weighing the risks and benefits of anti-CD20 monoclonal antibody therapy for individual patients in a shared decision-making process. For some IMIDs, there are few alternatives to anti-CD20 mAb therapy.

Moreover, delaying the administration of these agents as a way to minimize COVID-19 risk may put patients at risk of disease flare, irreversible organ damage and even IMID-related death.

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