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New data on COVID vaccination in multiple sclerosis (MS) patients have shown decreased humoral response in patients treated with the anti-CD20 antibodies ocrelizumab or rituximab, but not in patients treated with the similar drug, ofatumumab.

The results also show a decreased response to the COVID vaccination in some patients taking fingolimod.

The data comes from a new series of vaccinated MS patients from Madrid, Spain, presented at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) October 13-15.

Celia Oreja-Guevara, MD, Hospital Clínico San Carlos, Madrid, Spain, presented the data and concluded: “Currently approved COVID-19 vaccines appear safe in MS patients and are effective anti-CD20 in most patients – and S1P inhibitors (like fingolimod) need further investigation. “

“We showed that patients who received ocrelizumab or rituximab had very little or no antibody response to the COVID vaccination,” she added. “However, some previous studies in these patients have shown some T-cell response to vaccination and we are now looking into that.”

For the current study, the researchers analyzed the antibody response to the COVID-19 vaccination at week 3, week 6 and month 3 after the first dose in 165 MS patients and 200 healthy controls.

Of the MS patients, 120 received both doses of the mRNA vaccine and 42 received the AstraZeneca vaccine. The mean age of the MS patients was 45 years and that of the healthy controls was 46 years.

The side effects were similar in the two groups and no increase in relapse activity was seen in the MS patients.

The mean antibody titers were slightly lower in the MS patients compared to the healthy controls. After 3 weeks, the mean titers were 7910 AU / ml in the MS patients and 9397 in the healthy controls. After 6 weeks, the mean levels were 16,347 AU / ml in the MS patients and 18,120 in the healthy controls.

MS patients treated with interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine and natalizumab who received mRNA vaccines developed a similar humoral response after vaccination as healthy controls 3, 6 and 12 weeks after the first dose.

MS patients who received the AstraZeneca vaccine had a lower humoral response than those who received the mRNA vaccine, but the same effect was seen in the healthy controls.

However, patients who received the anti-CD20 drugs ocrelizumab or rituximab had a lower humoral response to the COVID vaccination. Only 3 out of 20 patients treated with ocrelizumab developed antibodies, but these patients had longer washout times (at least 6 months) between taking ocrelizumab and the COVID vaccine. All 6 patients treated with rituximab showed no antibody response to the COVID vaccination.

Oreja-Guevara also suggested that patients treated with ocrelizumab may have worse outcomes following COVID-19 infection. “In the first wave of infections in Madrid, we recorded 5 ocrelizumab patients with COVID-19, 4 of whom were hospitalized,” she noted.

“In patients receiving ocrelizumab, we have to try to keep a long period of time between being given this drug and being given the COVID vaccine. The longer the washout period, the more antibodies are seen, ”she said.

She found that two patients in the study received the COVID vaccine 1 year after being given ocrelizumab and had a normal humoral response, similar to the healthy control group.

The new anti-CD20 drug ofatumumab didn’t seem to affect the COVID vaccine’s antibody response as much as ocrelizumab or rituximab. In the current study, four out of five patients treated with ofatumumab showed an antibody response.

Oreja-Guevara suspected that this was probably because the B-cell depletion is not as strong with ofatumumab. “This drug is given every 4 weeks and it doesn’t use up all of the B cells and they are replaced pretty quickly,” she noted.

Fingolimod is another MS drug that appears to affect the antibody response to COVID-19 vaccination.

Oreja-Guevara described the response to the COVID vaccine in patients who received fingolimod as “very variable”. Of 16 fingolimod-treated patients, four developed no humoral response, seven had a weak antibody response, and five had a similar response to the healthy controls (three of these patients also had a previous COVID-19 infection). . The response to vaccination in fingolimod-treated patients did not appear to be related to lymphopenia.

The cellular response is also controlled by fingolimod. impaired

These data are consistent with those of another cohort from Israel previously reported.

In this study, published earlier this year, a team led by Anat Achiron, MD, Sheba Medical Center, Tel-Aviv, Israel, analyzed humoral immunity in 125 MS patients one month after the second dose of Pfizer COVID vaccine. A group of healthy, similarly vaccinated people served as controls.

The results showed that 97.9% of the control group had protective humoral immunity after vaccination, compared with 100% in untreated MS patients and 100% in MS patients treated with cladribine, but only in 22.7 % of patients treated with ocrelizumab and only in 3.8% of patients treated with fingolimod.

In ocrelizumab-treated patients, the failure of an adequate IgG immune response was independent of the absolute lymphocyte counts, which were in the normal range, or the time interval from the last ocrelizumab treatment dose, which was between 3.1 and 8.9 months, “what after.” suggests that the next dose needs to be postponed to allow for an effective humoral response after vaccination, “say the authors.

They find that the majority of fingolimod-treated patients in the study had low lymphocyte counts (< 1000 cells/mm3), which may be the cause for failing to mount an immune response. But even in the small group of fingolimod-treated MS patients with an absolute lymphocyte count > 1000 cells / mm3, no humoral reaction was detected.

At the ECTRIMS meeting, Achiron presented further results from this study on memory B and T cell responses to the COVID vaccine in these patients.

The results showed that COVID-specific B- and T-cell responses were only present in about half of the healthy volunteers, untreated MS patients, and those treated with cladribine.

While the B-cell response was almost completely impaired in the ocrelizumab patients, the T-cell response was present to the same extent as in the control group. But fingolimod patients showed no B or T cell responses.

Achiron concluded that patients receiving ocrelizumab should wait at least 9 months after the last dose before receiving a COVID vaccination, and that patients taking fingolimod should consider switching to another drug.

However, she noted that in this study, despite the lack of humoral cellular responses in the fingolimod group, there appeared to be no increase in COVID infection in patients taking fingolimod in a large registry study.

“That leads us to the idea that lymphopenia might not be the only story, and maybe innate immunity plays a role. We still don’t really know the answer to that.”

Achiron said she was also surprised to see that even untreated and healthy subjects did not develop full B-cell and T-cell responses after the double COVID vaccination. And similar results have been seen in patients recovering from natural COVID infection where the B-cell response is “not 100%,” she added.

“This hints at the clue that everyone may need a third vaccination, MS patients or not,” she concluded.

Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Presented on October 13th.

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