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Most vaccines, including the COVID-19 mRNA vaccines from Pfizer/BioNTech and Moderna, generally are safe for people with multiple sclerosis (MS), according to a prominent researcher in the field.

However, some MS disease-modifying treatments (DMTs) may affect COVID vaccine responses, which "may be influenced by the timing of the vaccine relative to treatment," said Amit Bar-Or, MD, of the University of Pennsylvania in Philadelphia, at ACTRIMS Forum 2021, the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.

There isn't a serious question about the COVID vaccines' safety in MS patients. "These are non-live, inactivated vaccines," he said. "The merits of protection from COVID by far outweigh any risk."

Rather, the issue is whether MS treatments that suppress certain elements of the immune system -- as many DMTs do -- will reduce the level of protection offered by vaccination.

How MS drugs may affect COVID-19 vaccine responses will depend on two things, Bar-Or said: which elements of the immune response the DMT affects, and when DMT effects take place in the time-course or cascades of cellular and humoral vaccine responses.

"Vaccine-induced neutralizing antibodies to the spike protein probably are important for effective protection from SARS-CoV-2 infection," he said. "B-cell depleting therapies -- the anti-CD20 drugs [ocrelizumab, rituximab, and ofatumumab], cladribine, or alemtuzumab -- likely will not impact pre-existing humoral immunity, but are expected to attenuate vaccine-induced antibody responses."

In the of tetanus, pneumonia, and other non-COVID-19 vaccines last year, relapsing MS patients treated with the anti-CD20 drug ocrelizumab (Ocrevus) had reduced immune response to vaccinations compared with untreated patients or patients treated with interferon beta-1a (Avonex, Rebif), but were "nonetheless able to mount humoral responses to the vaccines and neoantigen studied," Bar-Or pointed out.

While there's no information yet about the effects of MS drugs on COVID-19 vaccines, the general consensus is that some MS patients may want to coordinate vaccination and DMT timing, he said. Early guidance from a National MS Society task force about mRNA COVID-19 vaccine timing suggests the following, he added:

• For interferon beta-1a, interferon beta-1b (Betaseron, Extavia), glatiramer acetate (Copaxone, Glatopa), peginterferon beta-1a (Plegridy), teriflunomide (Aubagio), dimethyl fumarate (Tecfidera), natalizumab (Tysabri), and diroximel fumarate (Vumerity), no adjustments are needed, whether initiating or already on treatment.
• For fingolimod (Gilenya), siponimod (Mayzent), and ozanimod (Zeposia), "complete vaccine injections 4 weeks or more prior to starting DMT" when possible, Bar-Or said. "If already taking these DMTs, no particular adjustments are recommended."
• For ocrelizumab, rituximab (Rituxan), and ofatumumab (Kesimpta), vaccine injections should be completed 4 weeks or more prior to starting DMT, if possible. If a patient already is on ocrelizumab or rituximab, "consider starting the vaccine injections 12 weeks or more after the last DMT dose," Bar-Or said. With ofatumumab, which involves monthly injections, "consider waiting until prior to next DMT injection to initiate vaccines," he added. "And when possible, avoid resuming anti-CD20 therapy until 4 weeks following the second vaccine injection."
• For alemtuzumab (Lemtrada) and cladribine (Mavenclad), complete vaccine injections 4 weeks or more prior to starting DMT if possible: "If already taking these treatments, consider starting the vaccine injections at least 12 weeks or closer to 24 weeks when possible," Bar-Or said. "When possible, avoid resuming DMT until 4 weeks following the second vaccine injection."

These guidelines, while streamlined and preliminary, need further work, some neurologists pointed out. "The MS community is very knowledgeable and has shown many times that they can deal with complexity," said Gavin Giovannoni, MBBCh, PhD, of Queen Mary University of London in England, who wasn't involved with the presentation.

Because advice about DMT dosing during COVID-19 has safety implications, "it is sloppy and lazy to lump cladribine and alemtuzumab together," Giovannoni told MedPage Today. "These two drugs may have similar modes of action in terms of targeting memory B-cells in MS, but how they get there is very different. I can imagine the scenario of someone not being vaccinated when they should have been and then getting severe COVID-19 and dying."

Guideline updates are being discussed, including a possible separation of cladribine and alemtuzumab recommendations, Bar-Or noted. Importantly, patients may not have much choice about when they schedule their COVID-19 vaccine, he added.

"Patients in general are recommended to take it when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine to their DMT," he emphasized. "And, of course, patients are advised to work with healthcare providers to determine the best timing."

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