Timing of rituximab infusion not tied to risk for COVID-19 hospitalization

The timing of rituximab infusion or cumulative lifetime rituximab dose did not appear statistically significantly associated with risk for hospitalization for COVID-19 among patients with MS who received the drug before getting COVID-19.

However, researchers noted limited power of the study in which these results were reported.

“Rituximab therapy has been associated with more severe COVID-19 infection in persons with multiple sclerosis, although this finding was based on a small number of events,” Kyla A. McKay, PhD, of the department of clinical neuroscience at Karolinska Institutet in Sweden, and colleagues wrote in JAMA Network Open. “Further research is needed to evaluate the potential increased risk for severe disease. In this study, we examined the association between timing and dose of rituximab and hospitalization for COVID-19 across Sweden.”

The investigators conducted a nationwide nested case-control study with prospectively collected data from 3,391 individuals who participated in an observational drug trial cohort. Participants had received ongoing rituximab treatment and had COVID-19 onset as reported by a neurologist between March 1, 2020, and April 30, 2021. McKay and colleagues used logistic regression to relate the risk for hospitalization for COVID-19 to the time between the most recent rituximab infusion and the COVID-19 onset date and the total cumulative lifetime rituximab dose received. All participants with mild COVID-19 infection, which were those who did not require hospitalization, composed the reference cohort. The researchers adjusted models for age, sex and prepandemic Expanded Disability Status Scale score.

Results showed COVID-19 infection occurred among 326 (9.6%) participants during the study period. Of these, 172 (52.8%) received rituximab before COVID-19 onset. Twenty-six (15.1%) required hospitalization, five of whom were admitted to the ICU, and four of whom required ventilation. The researchers reported no deaths and observed no differences related to age, disease duration or disease course between those with COVID-19 requiring hospitalization and those with a mild case. Those with a mild case had a median time between most recent rituximab infusion and COVID-19 onset of 6.1 months, whereas this time was 4.6 months among those who were hospitalized, which was not a significant difference. Median cumulative lifetime rituximab dose was 3.5 g among those with mild COVID-19 vs. 3.3 g among those who were hospitalized. The researchers noted time from the most recent disease-modifying therapy infusion and cumulative lifetime dose of rituximab did not correlate with risk for requiring hospitalization.

Following the categorization of rituximab timing, individuals with an infusion less than 4 months compared with greater than 8 months before COVID-19 onset had increased risk for hospitalization; however, this association was not significant after adjustment for age, sex and Expanded Disability Status Scale score. Comparable results arose from sensitivity analyses of polymerase chain reaction-confirmed COVID-19 cases.

“The strengths of this study were the prospective collection of data, nationwide study population and high-quality data,” McKay and colleagues wrote. “The limitations included potential ascertainment bias given the awareness of an increased risk of infection associated with rituximab and missing information on known risk factors for COVID-19 severity, including smoking and comorbidity.

“In conclusion, large data sets with data capture that is less prone to surveillance bias and with access to a broader range of confounding factors are necessary to settle the question of whether continued use of rituximab during the COVID-19 pandemic increased the risk of severe COVID-19 infection,” they added.