MS Disability, Not Drug Therapy, Tied to Worse COVID-19 Outcomes

July 02, 2020

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In patients with MS, disability, age, and obesity were the main risk factors for COVID-19 of increased severity in a new French study.

The use of disease-modifying therapies did not appear to be associated with increased risk for severe outcome.

This "should reinforce the recommendation of not stopping current disease modifying therapy and not delaying treatment initiation in patients who have higher disease inflammatory activity, risk for relapses, or subsequent disability," the study authors state.

The study was published online in JAMA Neurology on June 26.

The data come from a French registry of COVID-19 cases in patients with MS that was initiated to determine the characteristics of COVID-19 in this population and to identify the risk factors for developing a severe form of this disease. The study included all MS centers in France.

Data were collected on patient demographics, current drug therapy use, Expanded Disability Severity Scale (EDSS) score before COVID-19, comorbidities, and the presence of known lymphopenia before infection.

The primary endpoint was clinical status at the most severe point of SARS-CoV-2 infection (on a 7-point COVID-19 severity score scale), where 1 indicated no hospitalization or limitations on activities and 7 represented death.

A total of 347 MS patients with COVID-19 were included, of whom 73 (21%) had a COVID-19 severity score of 3 or higher (needing hospitalization), and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0 – 9.5), and 82% of patients were receiving disease-modifying therapies.

Results showed there was a higher proportion of patients with a COVID-19 severity score of 3 or higher among those who were not taking disease-modifying therapies (46.0% vs 15.5%; P < .001).

But the authors, led by Céline Louapre, MD, L'Institut du Cerveau et de la Moelle Épinière, Paris, France, note that disease-modifying therapies are more frequently prescribed for younger patients, those with a relapsing form of MS, and those with a lower level of disability. In a multivariate analysis, no association was found between disease-modifying therapy and COVID-19 severity.

Multivariate logistic regression models determined that age (odds ratio [OR] per 10 years, 1.9); EDSS (OR for EDSS ≥6, 6.3) and obesity (OR, 3.0) were independent risk factors for a COVID-19 severity score of 3 or higher.

The EDSS was associated with the highest variability of COVID-19 severe outcome, followed by age and then obesity.

Additionally, the multivariate analysis carried out with a COVID-19 severity score threshold of 4 or higher (hospitalized and requiring supplemental oxygen) found male sex to be an independent risk factor for severe COVID-19, as well as age, obesity, and EDSS.

Of the 12 patients who died, most had a progressive form of the disease and a high EDSS.

"The fatality rate among patients who were hospitalized was higher for most age groups in patients with MS compared with the general population in France, suggesting an increased risk of death in patients with MS compared with the general population, which needs to be confirmed with large epidemiological studies," the authors comment.

Four patients were hospitalized in intensive care units but survived. Two received ocrelizumab and had obesity as a comorbidity. A third patient, who had primary progressive MS and was taking rituximab, had an EDSS of 5.5 and had no known comorbidities. The fourth patient had relapsing-remitting MS and was not receiving disease-modifying therapy.

"In this cohort, the exposure to disease modifying therapy and the level of immunosuppression were not factors that independently modified the risk of developing a severe form of COVID-19," the authors say.

However, they add: "Caution should be exercised when interpreting this result, because it is possible that a larger cohort could identify a subgroup of patients with 1 or more DMTs [disease-modifying therapies] that modify the risk of COVID-19. Therefore, the pooling of registries and/or replication of results in other cohorts from several countries will be important to reinforce this result."

Of the two patients who were receiving ocrelizumab and who developed acute respiratory distress syndrome, they write: "Although these 2 patients also had obesity, it cannot be excluded that their disease modifying therapy may have increased their susceptibility to COVID-19 severity."

They stress that serologic studies following SARS-CoV-2 infection will be crucial to determine the characteristics of the immune response with different MS therapies and in particular with anti-CD20 therapies, for which lower immune response to vaccination has been reported.

The researchers say it is "not surprising" that age and obesity were identified as independent risk factors for COVID-19 severity, inasmuch as both of these factors have been identified as major risk factors for adverse outcomes in the general population.

"With the EDSS being the independent variable with the highest explained variability on COVID-19 severity, this finding should lead to strengthening and sustaining precautions and barrier measures to limit the risk of COVID-19 infection in patients with high disability," they say.

Results Align With Other Data

Commenting for Medscape Medical News, Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Ohio, said he thought the study was well done.

"The conclusions largely align with other published (eg, the Italian experience) and not yet published registries and case series and our experience," he noted.

"MS and MS disease-modifying therapies do not appear to have a major effect on susceptibility to infection or risk of poor outcomes from COVID-19. The main risk factors appear to be the same as for the general population (age, male sex, comorbidities, lower socioeconomic status, less distancing) and level of MS-related neurologic disability," Cohen commented.

"In general, we have advised our patients to continue ongoing disease-modifying therapy. When indicated, we have started therapy, though with some consideration of the specific need and risks in the individual patient," he added.

The study did not receive specific funding. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono outside the submitted work.

JAMA Neurol. Published online June 26. Full text

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