Decreased COVID Antibody Response in MS Patients Taking Ocrelizumab

Deborah Brauser

May 13, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Dr Ilya Kister

Antibody response is reduced in patients with multiple sclerosis (MS) who take a specific disease-modifying therapy (DMT) while infected with SARS-CoV-2, new research shows.

An ongoing prospective study of patients with MS who were unvaccinated against the virus reveals those taking the DMT ocrelizumab (Ocrevus, Genentech) during COVID-19 infection had lower levels of antispike antibodies compared with those who were not taking the drug.

However, T-cell response did not differ significantly between treated and untreated groups.

"Preliminary results suggest that antibody and T-cell responses to SARS-CoV-2 persist in MS patients for 9 months or more following infection; and antibody, but not T-cell, responses appear to be attenuated in the ocrelizumab group," study investigator Ilya Kister, MD, NYU Langone Health, New York City, told attendees at the virtual American Academy of Neurology (AAN) 2021 Annual Meeting.

Multiple Assays

Since March 2020, about 15% of patients at the NYU MS Care Center have been infected with COVID-19. However, it was "unknown whether DMTs affect persistence of antibody and T-cell responses" to the infection, the investigators note.

Antibodies are proteins that can fight off viruses and infections.

For the current study, researchers assessed antibody and T-cell response differences between patients with MS who were taking DMTs during a COVID infection versus those not taking these medications.

Kister presented results from the first 212 patients enrolled in the ongoing study. All were unvaccinated adults with MS (mean age, 41 years; 70% women; mean MS duration, 11.5 years). Of these, 36% were treated with ocrelizumab — the most commonly used DMT in the group.

Most patients were infected during the first wave of the pandemic in spring 2020, Kister noted.

Test results were collected a mean 260 days after infection.

Serologic assessment of antibody responses to COVID nucleocapsid and spike proteins was conducted using Elecsys anti-SARS-CoV-2 S and N tests, the NYU multiplex bead-based assay, and live virus immunofluorescence-based microneutralization assay. T-cell responses were measured using the enzyme-linked immune absorbent spot (ELISpot) cytokine assay and the SARS-CoV-2 TruCulture assay.

Questions Remain

Results showed that "nearly all" patients with laboratory confirmed COVID-19 had antibody responses to infection, as shown on the NYU multiplex assay, including 89% of those treated with ocrelizumab versus 97% of those not treated with the drug, Kister reported.

However, the ocrelizumab group was significantly less likely to test positive for SARS-CoV-2 antibodies on the Elecsys test (58% vs 97%; P = .0004).

In addition, lgG antispike antibodies were significantly lower in treated versus untreated patients (P = .02), as were "median IC50 of neutralizing antibodies" (P = .02).

On the other hand, T-cell responses were detected at similar rates in the two groups. For those taking ocrelizumab versus those not taking the medication, the response rate was 80% versus 82%, respectively, on the ELISpot IFN-y; 86% versus 67% on the ELISpot IL-2; and 39% for both groups on the TruCulture assay.

"These responses were quite comparable," Kister said.

Asked during the question and answer session if there has been any research examining the impact of different medications on COVID-19 vaccine efficacy, Kister said he was not aware of any such data.

However, "we are going to do a study on response to vaccination in ocrelizumab-treated patients. We haven't enrolled anybody yet but we're all ready to go," he added.

Kister said he wasn't entirely surprised by the variation in the current study between antibody and T-cell responses.

"We've seen in previous vaccine studies that antibody responses are down in people with B-cells that are depleted; and T-cell response is not expected to be majorly affected in ocrelizumab patients, which is what we've seen," he said.

A Cautionary Tale?

Dr Barry A. Singer

Commenting on the findings for Medscape Medical News, Barry A. Singer, MD, director, The MS Center for Innovations in Care at Missouri Baptist Medical Center, St Louis, noted "at this point, we can see that patients who have already been exposed to the COVID-19 virus and on ocrelizumab can make a good T-cell response to the virus." This is especially important in patients with depleted B-cells, said Singer, who was not involved with the research.

"The bigger question that comes up is: Does that apply to vaccinations? Will the vaccine work if I'm on a B-cell depleting medication? This study did not answer that," although new studies on the issue have now started, he said.

"There's no harm in being vaccinated. The question is just: Will the vaccine work as effectively on certain disease-modifying therapies?" Singer asked.

Also commenting on the findings, John Corboy, MD, professor of neurology at the University of Colorado School of Medicine, Aurora, told Medscape Medical News he was impressed with the wide variety of tests used.

Dr John Corboy

"So it was relatively wide-ranging. It wasn't the largest study, but given the time frame, it's a pretty significant enterprise to be able to get all those patients and to get the tests done," said Corboy, who is also codirector of the Rocky Mountain MS Center at the University of Colorado.

He noted that the results showed variability between the antibody tests, but there were no differences in T-cell response between the treatment groups.

"That's mostly reassuring, but it's also a bit of a cautionary tale in the sense that there is some diminished response. And it's a reminder that we should consider all of the different medications and their potential effect on vaccines," he said.

The study was funded by an investigator-initiated grant from F. Hoffman-La Roche. One investigator is an employee of F. Hoffman-La Roche. Kister and the other investigators have reported no relevant financial relationships. Singer has reported no relevant financial relationships. Corboy reported he will be participating in a new vaccine study that will be conducted along with Kister's team of investigators.

American Academy of Neurology (AAN) 2021 Annual Meeting. Emerging Science session, P15.014. Presented April 18, 2021.

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