Rituximab, ocrelizumab pose risks in patients with MS and COVID-19

Rituximab and ocrelizumab appeared to increase risk for adverse outcomes among patients with MS and COVID-19, according to study results published in Neurology.

A prior study suggested disease-modifying therapies that involve immunomodulation or immunosuppression for treating MS may increase susceptibility. Other studies showed patients treated with rituximab or ocrelizumab had increased risk for severe COVID-19 and higher frequencies of hospitalization.

“Large and geographically inclusive cohorts are required to assess the risk of severe COVID-19 for specific DMTs [disease-modifying therapies],” Steve Simpson-Yap, PhD, MPH, of the department of medicine at the University of Melbourne in Australia, and colleagues wrote. “Accordingly, we established a global data-sharing initiative to investigate characteristics of COVID-19 severity in people with MS.

“We hypothesized that older age, progressive MS-phenotype and higher disability were associated with more severe COVID-19, while immunosuppressive DMTs (alemtuzumab/cladribine/fingolimod/ocrelizumab/rituximab) would be deleterious but those with less infection risk (interferons/glatiramer-acetate) would be associated with a less severe COVID-19,” they added.

Researchers aggregated data from 12 sources across 28 countries. They collected data on demographic, DMT and clinical covariates, as well as on COVID-19 severity outcomes, hospitalization, ICU admission, requiring artificial ventilation and death. They also used multilevel mixed-effects logistic regression that controlled for age, sex, MS-phenotype and Expanded Disability Status Scale to investigate characteristics of outcomes among patients with suspected (n = 657) or confirmed (1,683) COVID-19.

Results showed the following outcomes for suspected plus confirmed COVID-19 patients and confirmed-only COVID-19 patients, respectively:

• 20.9% and 26.9% were hospitalized;

• 5.4% and 7.2% were admitted to the ICU;

• 4.1% and 5.4% required artificial ventilation; and

• 3.2% and 3.9% died.

Factors linked to worse COVID-19 outcomes included older age, progressive MS-phenotype and higher disability score.

Researchers noted an association between ocrelizumab and rituximab and hospitalization (aOR=1.56; 95% CI, 1.01-2.41 and aOR=2.43,95%CI=1.48-4.02, respectively) and ICU admission (aOR = 2.3; 95% CI, 0.98-5.39 and aOR = 3.93; 95% CI, 1.56-9.89, respectively) compared with dimethyl-fumarate; however, only rituximab was linked to higher risk for artificial ventilation (aOR = 4; 95%CI, 1.54-10.39). Ocrelizumab and rituximab showed a correlation with hospitalization (aOR = 1.75; 95% CI, 1.29-2.38 and aOR = 2.76; 95% CI, 1.87-4.07, respectively) and ICU admission (aOR = 2.55; 95% CI, 1.49-4.36 and aOR = 4.32; 95% CI, 2.27-8.23, respectively) but only rituximab with artificial ventilation (aOR = 6.15; 95% CI, 3.09-12.27) compared with pooled other DMTs.

Ocrelizumab and rituximab had an association hospitalization (aOR = 1.86; 95% CI, 1.13-3.07 and aOR = 2.88; 95% CI, 1.68-4.92, respectively) and ICU admission (aOR = 2.13; 95% CI, 0.85-5.35 and aOR = 3.23; 95% CI, 1.17-8.91, respectively), but only rituximab with ventilation (aOR = 5.52; 95% CI, 1.71-17.84) compared with natalizumab. Researchers emphasized that associations persisted when restricting to confirmed COVID-19 cases.

They observed no links between DMTs and death. Upon stratifying by age, MS-phenotype and EDSS, they observed no evidence that DMT associations with COVID-19 severity suggested differential DMT allocation by underlying COVID-19 severity.

“These results agree with smaller cohort studies and suggest that the risk vs. benefit of continued or new exposure to CD20-depleting treatment strategies compared to other DMTs needs to be considered in the context of the ongoing COVID-19 pandemic,” Simpson-Yap and colleagues wrote.