Drug or no drug?

Here is My Question:
I have been on Rituxan since Oct. 2014. My initial dose was 1,000 mg. I had a second infusion in April 2015. 

I was diagnosed in 2006, with one relapse approximately two years later. I was on Copaxone for about three years, at which time I switched to Tysabri for 46 months, until I converted to JC+ and went onto Rituxan.

My MRI's are stable, showing no new lesions, no activity. I have no new symptoms. I will be 60 soon, and would like to consider the possibility of not staying on a DMD the rest of my life. i have made major changes in my diet, exercise regularly, have a meditation practice and in general do whatever I can to support my health and healing.

I see a very well known MS doctor out of state, and I have my MS doc in state who supports my being on Rituxan. One doctor has suggested I do my Rituxan infusion every six months. The other doctor has suggested I wait until my b count has repopulated to 25% of what it was prior to my first infusion and then do my infusion.

Given what I have shared, what would you advise and why? If you need more information to answer my question, please advise. Many thanks for this web site, and all that your provide for the MS community.

Answer:
There is no standard practice for Rituximab dosing intervals in MS patients. I can provide you with some guidelines but my answer will first assume that your MS was of sufficient severity to warrant both Tysabri and rituximab. If this assumption is correct it is probably not reasonable to consider getting off of treatment altogether.

We do not currently have a useful biomarker for monitoring dosing intervals with Rituximab or any anti-CD20 monoclonal antibody in MS patients. Traditionally, rituximab is dosed at 6 month intervals based on studies in rheumatoid arthritis (RA) patients. The 1000 mg dose completely deletes CD19 B Cell counts in 97 % of patients for a mean of 8 months. 

Different types of B cells return at different rates and it is not at all clear which type of B cell must be suppressed to have a positive treatment effect in MS. Disease activity tends to return within 2 months of the return of total B cell counts in RA patients, but there is a lot of variability. In the few MS studies done so far, there is no clear relationship between the return of B cell counts and the return of disease activity. My experience suggests that prolonged treatment with Rituximab causes a cumulative more sustained reduction in B Cell counts and an MS patient on treatment every 6 months for 18-24 months can begin to lengthen the interval between treatments over time.

Overall, three approaches have developed to manage this issue:

1. Treat regularly every 6 months. If you take this approach there is not a good reason to even measure CD 19 counts

2. Treat to a target. 

a. The target can be a return of disease activity, but I do not favor this approach given the current safety profile of Rtuximab

b. Treat until B cell counts begin to return. A 25 % return in B cell count is a reasonable approach. Using this approach I find myself retreating MS patients every 6 to 12 months when using a dose of 500 mg to 1000 mg

Good luck

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


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