Questions About Rituximab From A Neuro Pharmacist

Here is My Question:
I just asked a question about Rituximab after Tysabri. Relatedly, how do you dose the Rituximab and how long do you treat for. Also do you check CD19 CD20 levels to monitor? If so what are your targets? THANKS again--Neuro Pharmacist

Answer:
This is an extremely important question that must be answered by future clinical trials. The phase II rituximab trial in MS dosed patients with a single dual induction only (1000 mg X 2 doses separated by 2 weeks) with no re-treatment. There was no link between the return of CD19 positive B cells and the return of disease activity. In contrast the return of disease activity in other immunoglobulin mediated autoimmune disorders, such as neuromyelitis optica, appear to be linked to the re-emergence of CD19 + B Cells, particularly the CD27+ subset.

This leaves us with a significant predicament in typical relapsing MS; we do not know the minimally effective dose or an effective biomarker for treatment response or the need for re-treatment; we also can not use the “treat to target” approach advocated in rheumatoid arthritis patients since disease re-emergence is more abrupt and potentially more devastating in MS. Annette Langer Gould and I collaborated on a uncontrolled observational study in active relapsing MS patients receiving low doses of rituximab (100 mg in a single infusion) and demonstrated that even these doses were able to deplete CD19+ B cells for up to 3 months. Most of these patients remained stable on repeated infusions of the 100 mg dose every 4 to 6 months, markedly decreasing the total cumulative dose of rituximab.

For the time being, I use rituximab primarily as induction therapy in highly active, high risk MS patients before initiation of other standard disease modifying therapies. For NMO, I re dose patients with any reemergence of CD19 B cells.

Hope this helps.
Rip Kinkel

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