COVID vaccination in MS patients treated with DMT: new data

NATIONAL HARBOUR, Maryland ― The latest updates on the vaccine response to COVID-19 in patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that if patients do contract the virus, cases are mild and serious infections are rare.

However, the vaccine antibody response remains weaker with anti-CD20 therapies.

One of many late-breaking studies on these questions that were presented at the 2022 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) included over 100 MS patients who were treated with a variety of DMTs. .

The results showed that the antibody response rate was only 55% in people treated with anti-CD20 therapies, compared to 83% for those treated with other DMTs, including sphingosine receptor modulators. 1-phosphate (S1P).

Consistent with what has been observed in other studies, “Vaccine antibody responses were slightly lower in B-cell depleted patients than with other therapies,” said lead author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, University of Virginia College of Medicine, Fairfax, said Medscape Medical News.

Vaccine response

The researchers sought to assess detailed vaccine responses in 134 MS patients. Serum COVID antibody measurements were performed approximately 3 weeks to 4 months post-vaccination – and primarily after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD 52 and natalizumab (P

The highest prevalence of antibody response was seen in those taking immunomodulators; responses occurred in 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses were correlated with higher baseline immunoglobin levels (P = 0.01) and shorter treatment times.

“We found that longer total treatment duration and lower immunoglobulin levels tended to correlate with decreased immune responses,” Dave said.

“It is interesting to note that the delay between vaccination and the administration of [anti-CD20 drug] ocrelizumab did not appear to impact antibody responses,” Dave noted. He added that this is contrary to some previous studies that showed benefits if vaccination could be completed before starting ocrelizumab.

Sixteen participants tested positive for COVID-PCR in the previous 12 months. Although most infections were described as mild and self-limiting, four of the patients received outpatient treatment with monoclonal antibodies and one required hospitalization due to COVID.

“I think it is remarkable and reassuring that, overall, our patients had mild outcomes. This is consistent with how vaccines “work” and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dave said.

He added that he reassures patients who need high-efficacy therapies “that they should be using them.”

That being said, like in the general population, even vaccinated patients can contract COVID, he noted. “You can be sick and feel bad, but in general the number of hospitalizations is down from 2 years ago. We are seeing the same trends in MS patients, including lymphocyte-depleted patients B,” he added.

“To get to the question of whether patients lacking B cells behave exactly the same way as the general population, or even [with] other DMTs, we will need large multicenter prospective datasets,” Dave said.

Favorable Findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses in patients receiving S1Ps. It was feared that S1Ps would blunt antibody responses to COVID vaccinations.

The concern is their unique mechanisms of circulating lymphocyte sequestration, in particular the ancient non-selective modulator of S1P receptors. fingolimodsaid the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It seems that the problems with fingolimod could be related to the level of white blood cell sequestration, [which is] higher in fingolimod than newer S1P receptor modulators, and/or the outcome of S1P4 receptor modulation, which is not seen with newer selective drugs,” Kantor said. Medscape Medical News.

In a prospective observational trial of patients with RMS, among 30 participants treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL, versus a mean increase of 526.59 AU/mL in 30 patients not treated with ozanimod/DMT.

To date, only three patients in the study were taking ocrelizumab; for these patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Kantor says are generally considered protective, all but one patient tested positive on T-Detect, indicating vaccine protection.

“In this study, RMS patients treated with ozanimod had an antibody and T-cell response to COVID-19 mRNA vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up planned for December 2022.”

ponesimod results

In the other late-breaking study related to the S1P modulator, Janssen Research and Development reported on the antibody responses of patients treated with the S1P drug ponesimod in the phase 2 study AC-058B202.

The median exposure to ponesimod at the time of vaccination was 10.7 years (range: 9.8 to 11.8 years). There were 134 patients in the study. Of these, pre-vaccination and post-vaccination blood samples from 49 patients were tested for peak antibody concentrations.

Of these participants, 40 (81.6%) met the definition of response to COVID-19 vaccination, defined as seroconversion in the event of a negative pre-vaccination antibody test or a fourfold increase in antibody concentration in case of positive pre-vaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion after vaccination.

Twenty participants reported having had COVID before vaccination, while 17 had COVID after vaccination.

None of the cases were serious, severe or fatal, and none resulted in permanent discontinuation of treatment.

“In patients with RMS on ponesimod, the majority (>80%) appear to develop a measurable SARS-CoV-2 humoral response following vaccination against COVID-19,” the authors, led by Janice Wong, of Janssen Research and Development, LLC, write.

“Further investigations into the efficacy and safety of vaccination against COVID-19 in MS patients on ponesimod are warranted,” they add.

In a latest Genentech study, of 4,848 MS patients who were fully vaccinated during Delta and Omicron waves, 1.3% had a COVID-related hospitalization. Additionally, the rate of serious SARS-CoV-2 infections was very low (0.6%); there were less than 10 infections in each DMT subgroup. These patients included 585 (17%) treated with ocrelizumab, 238 (7%) treated with S1P receptor modulators, 33 (1%) treated with interferons, 1004 (29%) treated with other DMTs, and 1574 (46% ) for which no DMT has been recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those seen in the general population,” such as those who are older or have higher comorbidity rates, Preeti Bajaj, HEOR Team Leader, Neurosciences at Genentech, says Medscape Medical News.

“We believe [ocrelizumab] Treatment decisions should be made between a patient and their treating neurologist or other healthcare professional based on a patient-specific benefit-risk assessment,” Bajaj said.

Concerns remain

Commenting for Medscape Medical News, Bruce AC Cree, MD, PhD, professor of clinical neurology and director of clinical research at the University of California, San Francisco, Weill Institute for Neurosciences, described the overall anti-CD20 vaccine efficacy data as ” daunting” and said he was adjusting his own recommendations for these patients.

“Repeat vaccinations do not appear to stimulate humoral responses in B-cell depleted patients,” said Cree, who was not involved in the research.

In my personal practice, I have suspended dosing in my patients to allow B-cell reconstitution followed by revaccination,” he added.

Regarding S1P drugs, he noted that apart from fingolimod, “the frequency of antibody response appears to be better than initial reports. However, index values ​​are low and may not be protective.”

Overall, the take-home message for MS patients taking DMT should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Cree said.

“In some cases, temporarily interrupting treatment could be useful to help develop robust responses to vaccinations,” he added.

Dave reported no financial relationship regarding the poster, but is a paid speaker/consultant for Novartis, BMS, EMD Serono, Biogen, Alexion, Genentech, Horizon and Sanofi for their MS & NMO therapies. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS and Janssen. Cree has indicated that he is an unpaid ($0) consultant for BMS, the maker of ozanimod.

2022 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC): Late-Breaking Abstracts. Presented June 2, 2022.

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