Is there information on the long-term impact of B cell depletion therapies (whether treating MS or otherwise)?

Here is My Question:
Is there information on the long-term impact of B cell depletion therapies (whether treating MS or otherwise)? Specifically when the B cells are left to repopulate, do they become more inflammatory than before? What would be the rationale for these therapies if your disease could potentially be worse than before?

Answer:
This is an excellent question. First, we do not know of any rebound in disease activity as B cells repopulate. This suggests it is highly unlikely that the B cells that return are in some way more aggressive or harmful to you. In fact, there is no clear temporal relationship between the return of total B cells (so-called CD19 + cells) and the return of disease activity. People can go for long intervals after repletion of B cells without any return of disease activity. We can only say that a return of disease activity is more likely the longer the duration between infusions. There is evidence in other inflammatory conditions treated with anti-CD20 therapies (Ocrevus, Rituximab, Kesimpta and Briumvi are all anti-CD20 agents) that a return of disease activity is more likely once central memory B cells return. Whether this applies to Multiple Sclerosis is unclear at this time. Central memory B cells are a subset of total B cells that take longer to return than naive CD19+ B cells.

We also know that immunosuppression and secondary hypogammaglobulinemia are more likely with cumulative high doses of intravenous anti-CD20 therapies (particularly rituximab and Ocrevus; Briumvi is rather new with no experience to guide us at present). So far it appears that secondary hypogammaglobulinemia (one cause of immunosuppression and infections) is less common with low dose subcutaneous treatment using Kesimpta.

Answering your question directly requires us to gain a better understanding of the mechanism(s) of short and long-term benefit with anti-CD20 therapies. For instance, once we deplete your B cell population with these therapies, are the cells which return during the bone marrow repletion process less autoreactive and/or better regulated? If this were the case and we found a biomarker reflecting this improved regulation, we could personalize your treatment and avoid unnecessary prolonged B cell depletion and potential immunosuppression. Other individuals may require higher or more frequent doses for a desired benefit.

Hope this helps.

Revere P (Rip) Kinkel, MDProfessor of Neurosciences
Director of the Multiple Sclerosis Program
University of California San Diego
​#multiplesclerosis #Bcells #Bcelldepletion