MS Type, Anti-CD20 Therapies Tied to Higher COVID-19 Mortality Risk

Among people with multiple sclerosis (MS), a progressive disease type and the use of anti-CD20 therapies — such as ocrelizumab and rituximab — were associated with an increased risk of death from COVID-19, a new meta-analysis revealed.

“We hope that these findings … may help neurologists in optimizing the monitoring and treatment decision-making processes in this global crisis due to the pandemic COVID-19 outbreak,” the scientists wrote.

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The study, “Determinants of COVID‐19‐related lethality in multiple sclerosis: a meta‐regression of observational studies,” was published in the Journal of Neurology.

Overall, available data have suggested that people with MS have a 24% higher mortality risk from COVID-19 than the general population. Disease burden or immunosuppressive treatments have been thought to influence the increased mortality risk posed by COVID-19, but these relationships are not well established.

To better understand the risk factors, a team of researchers from Italy performed a meta-regression analysis — which combines and compares data across multiple studies — covering 18 research studies about COVID-19 in MS patients. The analyzed studies were published between January 2020 and July 2021.

Importantly, the majority of the data were collected during the first pandemic wave — before the anti-SARS-COV-2 vaccinations were available — the researchers said.

Data from a total of 5,634 patients from more than 13 countries were included in the analysis. Of them, 28.6% were male and the mean age was 41.8. Overall, 3,968 (70.4%) had a confirmed COVID-19 diagnosis and 1,666 (29.6%) had a suspected case based on clinical and/or radiological review.

Among the patients, 873 (15.5%) were hospitalized, and 111 deaths (1.97%) due to COVID-19 were reported.

Mortality was found to be associated with increased age — on average, greater than 43 years — and the presence of comorbidities, or co-existing medical conditions, both of which are also risk factors in the general population.

In studies where data were available regarding MS types, 15.4% of patients, or 699 of 4,529, had progressive forms of MS, which also was correlated with increased mortality. That finding is in line with observations from other infections, especially respiratory ones, in which patients with progressive disease also have an increased risk of mortality, the team noted.

“Clinicians and patients with MS should be made aware of a possible increased lethality of COVID-19 in case of advancing age, presence of comorbidity, and progressive disease course,” the researchers wrote.

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Higher mortality rates also were observed among people treated with anti-CD20 antibodies, such as Ocrevus (ocrelizumab) and rituximab, which target mature B-cells, a type of immune cell.

Prolonged treatment with anti-CD20 antibodies is associated with hypogammaglobulinemia —  a problem with the immune system that prevents it from making enough antibodies — and impaired B-cell recovery, two signs of immune deficiency. This immune suppression can potentially increase infection risk, according to the researchers.

Such therapies also could limit the effectiveness of the COVID-19 vaccines.

Thus, clinicians should consider modifying treatment with these anti-CD20 antibodies when possible, the team said.

“[Ocrevus] and rituximab should be started after anti-COVID-19 vaccination, unless the risk:benefit ratio supports the need for an urgent treatment,” they wrote. “In patients already on treatment with anti-CD20 agents, the timing of vaccination should be scheduled with a delay of at least 3 months from the last administration, according to the most recent recommendations.”

In contrast, treatment with interferon beta or Aubagio (teriflunomide) was associated with a decreased mortality rate, a result which is unsurprising, according to the researchers. Interferons are released in the body in response to viruses, and have been considered as a treatment for COVID-19 infection. It also has been hypothesized that Aubagio has antiviral activity.

The team noted, however, that their suggestions regarding treatment plans “came from expert consensus rather than clinical evidence, therefore they should be interpreted with caution and cannot be considered as guidelines until validation by ‘ad hoc’ studies.”

In conclusion, the researchers “identified clinical determinants for an increased lethality of COVID-19 in patients with MS. These determinants include age, presence of comorbidity, progressive disease course, and current treatment with anti-CD20 agents.”

Some data were not available in every one of the 18 studies, and could not be evaluated in the final analysis, the researchers emphasized. These features, including steroid exposure, the timing of some treatments, and the number of a type of immune cell called lymphocytes, each could still contribute to mortality risk.

Furthermore, the data were collected prior to the availability of the COVID-19 vaccines. “Future investigation is warranted to determine if the introduction of [anti-COVID-19] vaccines would alter our findings regarding both the increased death risk and lethality determinants of COVID-19,” the researchers concluded.