B cell Depleting therapies and the COVID 19 Pandemic

Here is My Question:
I recently asked the question about whether or not to delay my Ocrevus due to the coronavirus. I am in Louisiana and there is currently a case here now. I was considering getting an MRI to make sure I don’t have new or active lesions and possibly checking my B cell count. My questions are:

1. If my B cell count is around zero, how long would I expect it to take for them to be high enough to make me no longer immunocompromised?

2. If it will be low for a long time, would it even matter if i had the infusion now?

3. Is it worth checking the B cell count or do you feel that it is not useful and that we should just assume we are immunocompromised on Ocrevus regardless of the number?

4. At this point with the COVID19 spread, if I and MRI showed new or active lesions, would it still be more of a risk to get the infusion versus waiting a few months?

Thank you for your help. I have a terribly hard time getting through to my MS specialist and her office is not responsive to my questions.

Answer:
B cell Depleting therapies and the COVID 19 Pandemic

These are really good questions. All of them have been asked in one form or another lately by our MS patients receiving treatment with monoclonal antibodies that deplete CD20 expressing lymphocytes (predominantly B cells).  Let's begin with what we currently know about these therapies;

1. Anti-CD20 monoclonal antibodies (rituximab and Ocrevus) are very effective for relapsing forms of MS and mildly  effective for primary progressive MS patients under the age of 55. We do not know the effectiveness of this therapy in older patients (those over 55); This is important information when considering the potential upside of treatment in your situation
2. Treatment with anti-CD20 monoclonal antibodies, particularly repeated treatments every 6 months, increases your risk of upper respiratory tract infections and pneumonia. This risk is highest in older patients (over 55) and those with significant disability (requiring assistance to walk or Wheelchair bound). It is also higher in those with other medical conditions like diabetes, pulmonary disease or vascular disease and in smokers. The risk of respiratory infections is also higher if your IgG or IgM total antibody levels fall below the lower limit of normal. This is a common blood test your doctor can order. This is information to consider when determining the potential downside of treatment in your situation.

For those on treatment with anti-CD20 monoclonal antibodies already:

1. The benefits from a single infusion can last from 6 months to several years. There is no definite biological marker that tells us when the effects of a single infusion wears off, but a return of disease activity is more likely once central memory B cells return. These cells have certain markers on the cell surface (CD19+CD27+) and can be easily measure with a blood test. The duration of benefit may increase after many cycles of treatment. This means that a person who has already received greater than 2 cycles of treatment may be able go longer before needing another infusion compared to a patient who has received only 1 cycle of treatment. However, the risk of infections goes up with repeated cycles of treatment every 6 months.
2. The risk of complications from COVID 19 (corona virus) are expected to increase in those on regular infusions of anti-CD20 therapy. This is particularly true in those who are older, more disabled, have immunoglobulin deficiency or  have other disease mentioned previously. Again, this risk is further increased in smokers. This information can be used to decide if your definitely delay further cycles of treatment.

In general we are delaying anti CD20 treatments during the COVID 19 outbreak until there is a return of central memory B cells or even longer if other risk factors are present or the patient has been stable by MRI and clinical examination for over a year. Following this protocol many of our patients are going over 1 year without repeat treatment and sometime much longer.

​Revere (Rip) Kinkel MD
Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego