B-Cell Level May Affect COVID Booster Efficacy in MS

Kelli Whitlock Burton

June 02, 2022

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

Patients with multiple sclerosis (MS) treated with the B-cell-depleting medication rituximab who have not yet been vaccinated against COVID-19 should get the initial vaccination as soon as possible but wait to get a booster shot until B-cell levels increase, new research suggests.

In a prospective cohort study, 90% of patients taking rituximab whose B-cell level was at least 40 cells/µL had a sufficient antibody response to the Pfizer vaccine, whereas among those with lower levels, the antibody response was significantly lower.

Results also showed a wide variation in the length of time needed for adequate B-cell restoration. Some patients needed a year or longer for levels to become adequate.

The findings led the hospital where the study was conducted to suspend rituximab therapy until patients could be vaccinated. The findings also prompted researchers to call for new guidelines on vaccine scheduling that are based on B-cell levels and not on the current criteria of length of time since last treatment.

Dr Joachim Burman

"It's meaningless to just go by some recommendation covering time since the last treatment," study investigator Joachim Burman, MD, PhD, a consultant neurologist at Uppsala University Hospital and an associate professor Uppsala University, Sweden, told Medscape Medical News.

"It's misleading and potentially harmful for patients," Burman said.

The findings were published online May 11 in JAMA Network Open.

Finding the Cutoff

Drugs such as rituximab target CD20, a protein found on the surface of B cells, resulting in B-cell depletion.

Rituximab is the most common MS therapy used in Sweden. The drug is approved in the United States to treat rheumatoid arthritis and some forms of cancer, but it is not approved for treatment of MS.

Prior research showed that antibody response to COVID-19 vaccines was lower in patients receiving B-cell therapy than in the general population. That was not altogether surprising, given the fact that studies have found a similarly weakened antibody response to other vaccines.

But before now, there was no known B-cell threshold sufficient to mount an acceptable antibody response following COVID vaccination.

Researchers enrolled 67 patients in the study. Of those patients, 60 had received rituximab treatment, and seven had not.

Approximately 6 months after the last rituximab dose, the B-cell count was lower than 10/μL for 40% of patients. In that group, rituximab treatment duration was the only factor significantly associated with slower B-cell mobilization (median duration, 4.0 years, vs 2.1; P = .002).

Close Monitoring Needed

Six weeks after vaccination with tozinameran, the mRNA vaccine manufactured by Pfizer, 28% of patients failed to generate a sufficient antibody response. Among those patients, the median B-cell count was 22/μL, vs 51/μL for the remainder of the cohort (P < .001).

A cutoff value of 40/μL rendered adequate levels of anti-spike immunoglobulin G antibodies in 90% of patients and a strong response in anti-RBD antibodies in 72%.

Study participants did register an adequate T-cell response to the vaccine, suggesting at least some level of protection.

Because MS patients are at increased risk for serious illness from SARS-CoV-2 infection, the investigators recommend that patients with MS receive their initial COVID vaccines as soon as possible ― but that they should hold off on receiving a booster until their B-cell counts reach 40/µL.

Regarding when a clinician should re-vaccinate, "the results from our study strongly suggests that you should not do that right away or just follow some generic guideline," Burman said.

"You should closely monitor the B-cell values, and re-vaccinate once those B- cells hit the level of 40 cells/µL" he added.

Burman said he would expect that their findings would hold with the other mRNA vaccine and with any other B-cell therapy.

Too Soon for B-Cell Measures?

Commenting for Medscape Medical News, Robert J. Fox, MD, staff neurologist at the Mellen Center for MS and vice-chair for research at the Neurological Institute at Cleveland Clinic, Ohio, said the B-cell threshold identified in the study is much higher than what is typically seen in patients who undergo treatment with ocrelizumab, an anti-CD20 B-cell therapy approved in the US for treating MS.

Dr Robert Fox

"Decisions about treatment interval need to balance efficacy in treating MS with safety, including response to vaccines," said Fox, who was not involved with the research.

"Given the unknown efficacy of these extended intervals, I don't think we're at the point of making management recommendations based upon B-cell counts," he added.

And yet, Uppsala University Hospital, where the study was conducted, and other centers in Sweden decided to do just that. They suspended administering rituximab to patients with MS until the patients were vaccinated. For patients newly diagnosed with MS, therapy was initiated using another disease-modifying treatment, and for those who were due for a rituximab infusion, that treatment was delayed.

Only one patient experienced a mild MS relapse during the rituximab suspension, and that case went into remission within a week, Burman reported.

"Ever since the Bar-Or report showing that the humeral response to vaccines is markedly diminished in MS patients treated with anti-CD20 therapies, clinicians have been struggling to balance those safety concerns related to anti-CD20 monoclonal antibody treatments and the clinical benefit of this treatment class," Fox said.

"Given the uncharted waters of the COVID pandemic, clinicians made judgments and decisions as best they could, given the paucity of data," he noted.

"At this point, we don't know which decisions were right or wrong, but I certainly don't think we should judge clinicians for making decisions the best they could."

The study was funded by the Engkvist Foundation, the Marianne and Marcus Wallenberg Foundation, and the Swedish Society for Medical Research. Burman reported no relevant financial relationships. Fox has received consulting fees from Genentech/Roche, Biogen, and other companies that promote MS therapies.

JAMA Netw Open. Published online May 11, 2022. Full article

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