#AANAM – Ocrevus, Rituximab Linked to More Severe COVID-19 Cases in Italy

Editor’s note: The Multiple Sclerosis News Today team is providing in-depth coverage of the 2021 Virtual AAN Annual Meeting, April 17–22. Go here to read the latest stories from the conference.

Disease-modifying therapies (DMTs) that target CD20 are associated with worse outcomes from COVID-19 in multiple sclerosis (MS) patients, an analysis of patient data from Italy suggests.

Conversely, interferon-based DMTs and Aubagio (teriflunomide) were associated with less severe COVID-19 cases in the analysis.

These findings were shared in the presentation, “Different disease modifying therapies can increase or decrease Covid-19 severity in Multiple Sclerosis,” at the 2021 annual meeting of the American Academy of Neurology (AAN).

COVID-19 is the disease caused by the coronavirus SARS-CoV-2, which was first described in late 2019 and has since spread across the globe. As more data about COVID-19 is collected, researchers and clinicians are able to better understand what factors may increase an individual’s risk of severe disease.

MS is caused by the immune system launching an inflammatory attack that damages healthy tissue in the nervous system. Disease-modifying therapies have been proven in clinical trials to alter the disorder’s course. Broadly, currently approved DMTs  for MS work by suppressing the activity of the immune system.

Since the immune system is important for defending the body against viruses like SARS-CoV-2, there is a theoretical basis to presume that these DMTs might increase susceptibility to severe COVID-19.

Severe disease in COVID-19 is also tied to out-of-control inflammation, so it is also possible that some DMTs could be protective against severe COVID-19.

At AAN, Maria Pia Sormani, a professor of biostatistics at the University of Genoa, presented analyses that looked for connections between MS DMTs and severe COVID-19 using a method called ordinal logistic regression.

This type of statistical analysis is useful for assessing different levels of severity. In this case, the researchers looked at three levels: mild disease, moderate disease (characterized by pneumonia and/or requiring hospitalization), and severe disease (defined as admission to an intensive care unit and/or death).

Ordinal logistic regression was used to calculate the relative risk of disease worsening by one step — either from mild to moderate, or from moderate to severe.

Researchers looked at data covering 1,538 confirmed COVID-19 cases among MS patients in Italy for their analyses. Results showed that older age, male sex, greater disability, and more comorbidities (health conditions other than MS) all were tied to a significantly higher risk of severe COVID-19, which is similar to results of other analyses done in the general population and among MS patients.

Compared with untreated MS patients, however, treatment with anti-CD20 DMTs was associated with a roughly two times greater risk of severe COVID-19. Treatment with interferons, conversely, was associated with about a one-third lower risk of severe COVID-19. Both values were statistically significant, which means that mathematically, it is highly unlikely the results are due to random chance.

Anti-CD20 therapies are a DMT class that work mainly by killing immune B-cells, which are responsible for making antibodies; examples include Ocrevus (ocrelizumab) and rituximab. Interferons are a kind of DMT that mimic the activity of immune signaling molecules to dampen the immune attack; examples include Avonex, Rebif, and Betaseron.

Further statistical analyses showed a similar likelihood of severe COVID-19 among patients taking Ocrevus or rituximab (which is used off-label in MS), and indicated that the risk of severe COVID-19 was higher the longer a patient had been undergoing treatment with an anti-CD20 DMT. Prior studies have also shown a connection between anti-CD20 DMTs and severe COVID-19.

Of note, treatment with Aubagio (teriflunomide) was associated in the analyses with a roughly 50% reduced risk of severe COVID-19. This difference was not statistically significant, but it was close.

Treatment with a steroid called methylprednisolone — which is not considered a DMT for MS — within a month of COVID-19 symptoms beginning was associated with a more than two-fold, significantly higher risk of severe COVID-19.

In the Italian dataset used for analysis, the rate of intensive care unit admissions was 0.7%, and the death rate was 1.6%. These rates are comparable to what has been reported for MS patients in France who develop COVID-19.

However, for U.S. patients with COVID-19, “the intensive care unit admission rate was about five times higher than in Italy and France, and the death rate was two times higher,” according to Sormani — even though hospitalization rates in all three countries were similar (11% to 14%).

Sormani added that caution should be taken when making comparisons among datasets, since other factors are likely at play. She also emphasized that the scientific understanding of COVID-19 will continue to be refined as more data are collected.