COVID Booster May Benefit Patients on Anti-CD20 Therapy

Multiple sclerosis (MS) patients with weak immune responses to COVID-19 vaccines are more likely to respond successfully to the booster shot if they are receiving an anti-CD20 therapy compared with those on Gilenya (fingolimod), according to a small study in Norway.

These early findings suggest that booster shots should be considered among MS patients on anti-CD20 therapy who previously showed poor responses to COVID-19 vaccines, the researchers noted.

The study, “Immunogenicity and Safety of a Third SARS-CoV-2 Vaccine Dose in Patients With Multiple Sclerosis and Weak Immune Response After COVID-19 Vaccination,” was published as a research letter in the journal JAMA Neurology.

COVID-19 vaccines work by training the body’s immune system to recognize SARS-CoV-2, the virus that causes the disease, allowing a faster and more potent immune response in case of infection that has the potential to prevent severe disease.

As such, treatment with immunosuppressive medications — the mainstay approach in MS — can reduce the effectiveness of COVID-19 vaccines, lowering their protection against severe disease.

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Previous studies have suggested that about 80% of all MS patients treated with Gilenya or anti-CD20 therapy “have weak [antibody-based] immune responses after 2 doses of messenger RNA (mRNA) COVID-19 vaccines,” the researchers wrote.

Currently approved mRNA COVID-19 vaccines include Comirnaty, developed by Pfizer and BioNTech, and Spikevax, developed by Moderna.

Gilenya, initially developed by Novartis and also available in generic versions, is an oral MS therapy that works by “trapping” immune cells in lymph nodes, thereby preventing them from reaching and causing damage to cells in the brain and spinal cord.

Anti-CD20 therapies for MS — such as Kesimpta (ofatumumab), Ocrevus (ocrelizumab), and rituximab, used off-label  — work by promoting the death of immune B-cells that are responsible for making antibodies.

Notably, the safety and efficacy of a third vaccine dose in this group of MS patients treated with Gilenya or anti-CD20 therapies “is largely unknown,” the researchers wrote.

To address this, a team of researchers in Norway evaluated whether a booster shot promoted a normal immune response in 130 MS patients (97 women and 33 men) who were on these therapies and failed to successfully respond to two doses of COVID-19 vaccines.

All patients, enrolled at three Norwegian university hospitals, were participating in an observational study evaluating immune responses after two doses of mRNA vaccines (most commonly Comirnaty).

Patients’ median age was 47.5 years, and 87.7% had relapsing-remitting MS. Most (77.7%) were on anti-CD20 therapies (rituximab in 99% of them), while 22.3% were treated with Gilenya.

Vaccine responses were considered weak when antibody levels against the virus were lower than 70 arbitrary units (AU) and absent when levels were below 5 AU. After the initial round of vaccination, no vaccine response was detected in 61.5% of patients, while 38.5% showed weak responses.

All patients were offered a third dose (either Comirnaty or Spikevax) at a median of 84 days (nearly three months) after full vaccination. Antibody-based immune responses to the booster shot were assessed after a median of 22 days, a slightly shorter interval than that after the full vaccination (median of 39 days).

Results showed that after full vaccination, mean levels of anti-SARS-CoV-2 antibodies were 8.9 AU among patients on anti-CD20 therapies and 9.2 AU among those treated with Gilenya.

After the third shot, however, these levels increased significantly to 49.4 AU in the B-cell depleted group and 25.1 AU in the Gilenya group. Also, nearly one-quarter (24.8%) of patients on anti-CD20 therapies and two (6.9%) Gilenya-treated patients showed normal immune responses to the vaccine.

The researchers found no association between antibody responses and time from last dose of anti-CD20 therapy or treatment duration.

Notably, a higher number of lymphocytes, a type of immune cell that also includes B-cells, was associated with better antibody-based responses and also with more adverse events, which most often were temporary local pain and fatigue — common side effects of COVID-19 vaccines.

No patient experienced serious side effects events after the booster shot.

These findings showed that “a third dose of the mRNA COVID-19 vaccine was safe and associated with modestly increased levels of anti–SARS-CoV-2 … antibodies in patients with reduced protective [antibody-based] immunity” after full vaccination, the researchers wrote.

Notably, “a higher proportion of patients who were treated with anti-CD20 therapy experienced a better antibody response than patients treated with [Gilenya],” they added.

“A 25% increase in the number of patients who [developed normal immune reactions] after revaccination and who were treated with anti-CD20 therapy may be of clinical relevance, as these patients have an approximately threefold higher risk of developing serious COVID-19,” the team wrote.

“Our study results suggest that revaccination of these patients should be considered,” they added.

The researchers noted, however, that antibody levels after vaccination “are not fully predictive of protection against infection and that levels lower than the applied cutoff may also be protective.” In addition, immune responses against SARS-CoV-2 likely involve T-cells, another type of immune cell.

Larger studies are needed to confirm these findings.