Do I need to coordinate COVID vaccination timing with the timing of my DMT dose?

Here is My Question:
My question is about Ocrevus and the timing of a COVID vaccine.

A few days ago MedPage Today wrote:
"Patients taking ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), ocrelizumab (Ocrevus), or rituximab (Rituxan) may need to coordinate vaccination timing with the timing of their DMT dose."

I've read similar elsewhere, with guidance from neurologists recommending taking the vaccine at least six weeks before or after an Ocrevus infusion.

What is your advice?

Answer:
The appropriate timing of viral vaccination, specifically vaccination against COVID19, is a subject of significant concern to specialists treating people with immune subset depleting therapies, including the disease modifying therapies listed in your question. 

Immune depleting therapies are given infrequently because it takes many months or years for the immune cells to be replenished by bone marrow derived stem cells. The time course of individual immune cell subset repletion varies with different treatments and how they are administered: dose, frequency and route of administration can affect the repletion timecourse. 

Anti-CD20 monoclonal antibody treatments (e.g., Rituximab, Ocrelizumab and ofatumumab) are a case in point. These treatments specifically target and destroy B cells expressing the CD20 'target' on their cell surface. This includes both naive B Cells and memory B cells.  As these names imply naive B cells are important for learning about new viral infections and are required to mount strong antibody responses to viral vaccination. Memory B cells are created by exposure to vaccinations or native viruses; these cells allow you to respond quickly to eliminate a virus and other pathogens before they make you sick. Memory B cells, however, are a two-edged sword; they are also involved in autoimmunity, and their depletion by these therapies may be the main beneficial mechanism of action in diseases like Multiple Sclerosis or Neuromyelitis Optica. 

Naive B cells will return much earlier than memory cells and we can take advantage of this differential repopulation of B cell subsets in our vaccination protocols by vaccinating people after naive B cells return but before they are repopulated with memory B cells that can trigger autoimmunity. 

How do you know the sweet spot for vaccination after receiving B cell depleting therapies? One way is to measure B cells subsets after treatment with simple blood tests. For instance, after treatment with Rituximab and Ocrelizumab, naive B cells often start to return within 6 months, but memory B cells can take more than 12 months to start to return. If your doctor is unable to measure B cell subsets, he or she can simply measure total CD19+ B cells every 3 months after a treatment. Initially, there will be no CD19+ B cells detected at all but once the lab begins to see CD19 + B cells in your blood sample, the cells will only be naive B cells.

In practice it is almost impossible to time your treatments precisely for vaccination. You should take comfort in several facts about the immune system response to viruses before this worries you too much. First, cytotoxic CD8+ T cells, which are not even targeted by anti-CD20 monoclonal antibodies, are created by vaccination and are the main line of defense, along with cells of the innate immune system, against respiratory virus like COVID19. In fact, it is the impaired innate immune response in the elderly that is partly responsible for the severity of COVID19 infections in older people. Second, we know that people receiving anti-CD20 therapies can mount antibody responses to vaccines; although these antibody responses tend to be muted, they are often strong enough to be protective.

You should also take comfort in the fact that retreatment with immune depleting therapies can often be delayed for long intervals without your MS getting worse. It is a little trickier to delay these treatments with other conditions like Neuromyelitis Optica but some delay is still possible.

So at present we are delaying anti-CD20 therapies whenever possible to allow for COVID19 vaccination during a period of naive B cell repletion. If this is not possible, we are not recommending any significant delay in vaccination (no more than 8-12 weeks) but do recognize that people vaccinated after an anti-CD20 therapy will likely require booster vaccines in the future.

Please remember that regardless of your vaccination status, your main line of defense against COVID19 is wearing a mask and staying away from people who may be infected, especially in enclosed spaces like homes or restaurants, for more than a few minutes.

Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego