Italy study ties Covid severity to anti-CD20 drugs, recent methylprednisolone

Disability and advanced age were linked to severe Covid-19 outcomes including death in multiple sclerosis (MS) patients, registry data from Italy showed.

Among 835 MS patients with suspected (n=565) or confirmed (n=270) Covid-19, 11 of 13 deaths occurred in persons with advanced disease and disability, reported Marco Salvetti, MD, of Sapienza University in Rome, Italy, and researchers for the Musc-19 Study Group, in Annals of Neurology.

“We reran all the main analyses on the subgroup of confirmed cases, obtaining similar and even stronger results, despite the smaller sample size,” the researchers wrote. “These findings strengthen the need to enforce prevention strategies for people with advanced disability and older age during the pandemic.”

The researchers grouped Covid-19 outcomes of MS patients into three severity categories. — the highest severity level was death or ICU admission, intermediate was diagnosis of pneumonia or hospitalization, and lowest was milder disease with no need for hospitalization or documented diagnosis of pneumonia.

Overall, the findings indicated “an acceptable level of safety of therapies with a broad array of mechanisms of action,” Salvetti and colleagues noted.

After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale (EDSS), disease duration, body mass index, comorbidities, and recent methylprednisolone use, severe Covid-19 was seen more frequently in MS patients treated with anti-CD20 drugs (ocrelizumab or rituximab) than all other disease-modifying therapies (DMTs) (OR 2.37,95% CI 1.18–4.74; P=0.015).

A total of 89 patients in the study were treated with ocrelizumab, and five were treated with rituximab. While use of anti-CD20 treatment for 6-12 months showed no significant association with severe Covid-19 outcome, durations over 12 months conferred three times the risk (OR 2.98, 95% CI 1.37-6.46; P=0.006).

In other studies, Covid-19 outcomes of MS patients on anti-CD20 drugs have shown mixed results. “Smaller case series suggested an increased susceptibility to Covid-19 in people with MS taking B-cell–depleting monoclonal antibodies, without major effects on the severity of Covid-19,” Salvetti and colleagues wrote.

Guidelines from the National MS Society in the U.S. have suggested there is “some evidence that therapies that target CD20 — ocrelizumab (Ocrevus) and rituximab (Rituxan) — may be linked to an increased chance of having a more severe form of Covid-19.” Published data from ongoing clinical trials of ocrelizumab, the drug’s post-marketing safety database, and electronic health records have indicated that Covid-19 in ocrelizumab-treated MS patients is predominantly mild to moderate in severity, with most patients not requiring hospitalization.

Links between MS disability and Covid-19 severity have also been identified in other studies, including the Covisep registry in France that showed EDSS scores and obesity were independent risk factors for severe Covid-19 infection. In the French study, DMT exposure was not included in the multivariate model, Salvetti and colleagues pointed out. “The sample size did not allow drawing conclusions about the association of DMTs and Covid-19 severity,” they wrote.

In the Italian registry, MS patients had Covid symptoms between January and September 2020 and were followed until death or recovery. Median age was 45 and 70.3% of the cohort was female with a median EDSS of 2. Most patients (82%) were being treated with an MS DMT at the time of presumed Covid-19 symptom onset. Confirmation of Covid-19 was established in 33.1% overall through swab testing or serologic tests after recovery.

Overall, 11.7% of MS patients had radiologically documented pneumonia, 11.4% were hospitalized, and 4.5% were admitted to an ICU.

Of the 13 (1.54%) participants who died, 11 had progressive disease. Eight patients who died were receiving no MS therapy. The median age of MS patients with Covid-19 who died was 63, versus a median age of 45 for those who recovered.

No pneumonia, hospitalization, ICU, or death related to Covid-19 was seen for MS patients treated with cladribine (n=11) or alemtuzumab (n=14) in the study. Among 73 patients on interferon, no ICU admissions or deaths were recorded.

Previous methylprednisolone use in the month before Covid-19 symptom onset (n=26) was associated with severe Covid-19 outcome (OR 5.24, 95% CI 2.20–12.53, P=0.001). “This aspect was not considered in previous reports, is in agreement with data in other autoimmune diseases, and is relevant in assessing the risk of DMTs (i.e., Covid-19 risk versus steroid-sparing potential),” the authors observed.

A limitation of the study is the inclusion of suspected Covid-19 cases in the study, which may have introduced bias, Salvetti and co-authors acknowledged. “We took the decision of including suspected cases because, during the pandemic peak in Italy, only the most severe cases (often after hospitalization) were tested,” they pointed out. “Hence, including only confirmed cases would have limited the representativeness of our sample.”

  1. Disability and advanced age were linked to severe Covid-19 outcomes in MS patients, including death, registry data from Italy showed.
  2. After adjustment, severe Covid-19 was seen more frequently in MS patients treated with anti-CD20 drugs (ocrelizumab or rituximab) than all other disease-modifying therapies. Previous methylprednisolone use in the month before Covid-19 symptom onset also was associated with severe Covid-19 outcome.

Paul Smyth, MD, Contributing Writer, BreakingMED™

The Musc-19 Study Group acknowledged Roche for donating the web-based platform for data collection.

Salvetti reported no disclosures.


Cat ID: 36

Topic ID: 82,36,730,933,125,190,926,36,192,927,151,928,925,934