Extended interval dosing of natalizumab

Bomprezzi R, Pawate S. Extended interval dosing of natalizumab: a two-center, 7-year experience. Ther Adv Neurol Disord. 2014;7(5):227-31

BACKGROUND:The enthusiasm for natalizumab, a highly efficacious agent in the treatment of multiple sclerosis (MS), has been tempered by the risks of progressive multifocal leukoencephalopathy associated with its use, and strategies to minimize those risks are of great interest. Extended interval dosing (EID) has been proposed as a way to maintain the efficacy of natalizumab while reducing exposure to it. We reviewed a cohort of patients who received natalizumab at 6-8-week intervals instead of the typical infusions every 4 weeks with the goal to assess if patients on EID had an increase in clinical relapses.
METHODS:This is a retrospective review of all patients with MS treated with natalizumab at two MS centers where patients were offered the opportunity to switch to an EID every 6 or 8 weeks.
RESULTS:A total of 361 patients received natalizumab for 22 ± 13 months (minimum duration 6 months). Of these, 96 patients received EID natalizumab at some point for 20 ± 11 months (minimum duration 6 months). Over the study period, there was no significant difference between the relapse rate in the monthly dosing (13%) and the EID (13%) groups of patients.
CONCLUSION:Natalizumab is effective in controlling MS as very few clinical relapses were observed in our dataset. We found that EID did not compromise the treatment effect as measured by relapse rate and no significant breakthrough disease activity was observed. EID is an optional regimen for maintenance natalizumab therapy, but prospective studies are warranted to determine its efficacy.



Tysabri is typically administered every month, but this study looked and found that there was no more disease breakthrough if the interval between injections was extended to 6-8 weeks.  We know that from switching tysabri that disease returns once you stop and it takes a few weeks for the tysabri to get out of your system. 

If we wanted to be scientific about this, as we know that tysabri works because it blocks CD49d/VLA-4 on white blood cells. If we added a labelled antibody against CD49d and it could not bind because tysabri is working, with time new CD49d would be produced and then the labelled antibody would bind. Once a certain level of free CD49d is present, disease can return. So you could check this with a blood sample. It would take about 30-40min for me to do it and you could know if you are an individual you removes tysabri from the system quickly where EID may not be appropriate or someone who does this slowly and where EID may be more appropriate. The cost o the extra tests could be offset by reduced drug cost.However, its in the Interest of Biogen to sell you as much drug as possible. Look at Teva...they spent years telling you to inject daily yet once their patent for Copaxone runs out they come up with a formulation that only requires 3 times a week injections. 

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