B-Cell Targeted Therapy Linked With Severe COVID-19 Among Patients With Arthritis

By Lorraine L. Janeczko

October 11, 2021

NEW YORK (Reuters Health) - In patients with inflammatory arthritis (IA), B-cell-targeted therapy is linked with severe COVID-19, a new study from France shows.

"These results strongly indicate the increased risk of severe COVID-19 in patients receiving B-cell targeted therapy. Among patients with IA, those receiving rituximab should be prioritised for vaccination against SARS-CoV-2, sufficiently in advance of treatment infusion/reinfusion," researchers write in Annals of the Rheumatic Diseases.

"These results confirm previous retrospective studies and declarative registries," senior study author Dr. Jacques-Eric Gottenberg of Hopitaux Universitaires de Strasbourg told Reuters Health.

"Patients should be vaccinated before rituximab to avoid the risk of severe COVID," he urged by email.

Dr. Gottenberg and his colleagues collected data from September 1, 2019 - five months before the first outbreak of COVID-19 in France, ensuring that all enrolled patients had been exposed to a biologic before the pandemic began - to January 1, 2021.

To limit selection bias, recall bias, and missing data, they investigated all 1,116 patients with IA receiving intravenous biological agents (392 treated with rituximab, 105 with abatacept, 449 with infliximab, and 170 with tocilizumab) at seven clinical treatment centers in France.

The team searched for PCR-confirmed SARS-CoV-2 resulting in hospitalization or death. They found 10 cases of severe COVID-19: nine in patients treated with rituximab (2.3% of all patients treated with rituximab), and one in a patient given infliximab (0.1% of patients taking biological agents other than rituximab, and 0.2% of patients taking infliximab). Four deaths, unrelated to COVID-19, occurred during follow-up.

In univariate analysis, the proportion of cases hospitalized for COVID-19 was 9/392 for patients treated with rituximab compared with 1/724 for those given other biological agents (odds ratio, 8.5; 95% credibility interval, 2.6 to 38.6).

In multivariate analyses, rituximab was the only factor significantly linked with risk of being hospitalized for COVID-19 (OR, 7.7). In patients hospitalized for COVID-19, the median interval between last infusion and infection was 3.5 months. One patient received intensive care.

"This study adds to a growing and important body of literature indicating that patients on certain biologic DMARDs (disease-modifying antirheumatic drugs) - in this case rituximab and other B-cell-depleting agents - are at higher risk for poor outcomes if they contract COVID-19," said Dr. Zachary Wallace, a rheumatologist at Massachusetts General Hospital in Boston, who was not involved in the study.

"While this nice study improves upon the limitations of previous investigations, additional studies are needed to validate these findings in larger cohorts," he told Reuters Health by email.

"B-cell-depleting therapies like rituximab are frequently used to treat a variety of autoimmune conditions, including anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, rheumatoid arthritis, and multiple sclerosis. These findings have important implications for how we counsel patients on these medications during the ongoing pandemic," he explained.

"They also raise important questions about how we should manage the elevated risk of poor outcomes, especially given recent reports of reduced vaccine efficacy, including severe breakthrough infections, in patients on B-cell-depleting therapies," he added.

"Patients treated with B-cell-depleting therapies like rituximab may require other strategies, like pre-exposure prophylaxis with monoclonal antibodies against SARS-CoV-2, booster vaccines, and regular masking and social distancing when possible," Dr. Wallace advised. "Many providers are also increasingly reconsidering the way in which they use B-cell depletion during the pandemic and changing the dosing frequency of these medications."

Dr. Peter M. Izmirly, a rheumatologist and an associate professor of medicine at NYU Langone Health in New York City, said, "It is concerning that patients on rituximab are having poor outcomes if they get COVID-19. I had a 30+- year-old-rheumatoid arthritis patient die from COVID-19 while on rituximab."

"Rituximab has also been shown in several studies to blunt COVID-19 vaccine efficacy, which adds to the concern for both the patients on the medication and the physicians caring for them," Dr. Izmirly, who also was not part of the study, told Reuters Health by email.

The study did not receive commercial funding.

SOURCE: https://bit.ly/3l9igYu Annals of the Rheumatic Diseases, online September 23, 2021.

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