Questions about Rituxan and Multiple Sclerosis

Here is My Question:
Is there an increased risk of relapse after stopping Rituxan the way there is with Tysabri? Second, does Rituxan preclude patients from taking other drugs such as Tecfidera or even Tysabri and others in the future? Third, does the JCV+ antibody test done with Tysabri also mean a person has that same risk of PML with Rituxan?

Answer:
These are all very good questions for which we currently have only partial answers.

• Is there an increased risk of relapse after stopping rituximab?  Current evidence suggests that the return of disease activity after treatment with rituximab does not predictably follow the return of CD20 positive B cells to the circulation. In other words the return of MS disease activity is not predictably linked to the loss of the main biological marker of Rituximab treatment. In contrast the return of disease activity following cessation of treatment with Tysabri is more predictably linked to the loss of the biological effects of Tysabri treatment. Furthermore, the main phase II study of Rituximab treatment in relapsing MS did not report any rebound in MS activity as the effects of rituximab wore off during the follow-up phase. In fact the benefits persisted up to a year after the two Rituxmab treatments were administered at study onset.

• Does rituximab preclude MS patients from taking other MS drugs in the future?  We have no evidence that rituximab treatment precludes patients from receiving other treatments in the future. However, Rituximab in combination with other immunosuppressive treatments may led to an increased risk of infections including rare infections like PML. This has certainly been the case when rituximab has been used in combination with immunosuppressants and chemotherapies to treat other conditions. Only time and further studies will tell if Rituximab used in combination with other MS treatments increases the risk of these rare complications.

• Does the JCV antibody test done with tysabri also mean that a person has the same risk of PML with other treatments like Rituximab?  The answer is no. The JCV antibody test assesses the risk of PML on Tysabri treatment only. The risk of PML with other treatments, including Rituximab is very small (estimated at < 1 in 10,000 ). Since more than 50% of patients are JCV antibody positive, it is hard to imagine how the results of this test could have a meaningful impact on PML risk with Rituximab treatment. In contrast the risk of PML in the entire Tysabri population is at least 10 fold higher (1 in 1,000) than with rituximab treatment.
  

All of these answers must be tempered with some degree of caution as there here have been limited controlled studies of rituximab treatment in MS patients . For the time being these are the best answers that I can provide based on the evidence available.

Rip Kinkel, MD