Wednesday, 18 September 2013

Natalizumab holiday: when does the shredder come back

The shredder is back about 12-16 weeks after stopping natalizumab. #MSBlog #MSResearch

"This study is using science to tell us that if you switch from natalizumab to fingolimod after a prolonged washout to allow the level of saturation of the white cells to drop below a certain level you get rebound. There is now good evidence that you should switch within 8 and preferably 4 weeks after your last natalizumab infusion to fingolimod. This allows fingolimod time to start working before natalizumab is out of the system and hence reduces the chances of rebound. The danger of doing this is that if you have subclinical or asymptomatic PML this will the carry-over onto to fingolimod. This actually has already occurred in 2 MSers. To prevent so called 'carry-over' PML I recommend a baseline MRI and lumbar puncture with CSF analysis to reduce the chances of carry-over. We know from other studies that when you stop natalizumab MS activity rebounds at 3-4 months after your last dose. It takes fingolimod about 2 months to start working fully therefore it makes sense from a pharmacodynamic (big word the pharmacologists use to describe the timing of a drug's action) perspective to start fingolimod with 4 weeks of your last dose of natalizumab."

"If you want to switch to alemtuzumab will this advice change? Possibly. Alemtuzumab unlike fingolimod is irreversible; once you have had it you can't undo its affect. So if there is carry-over PML you would be in serious trouble. Why? You need your immune system to recover from PML; it takes 3-12 months for your immune system to reconstitute post alemetuzumab and this would be a very long time in the life of a PMLer."

Epub: Wipfler et al. Natalizumab saturation: biomarker for individual treatment holiday after natalizumab withdrawal? Acta Neurol Scand. 2013 . doi: 10.1111/ane.12182.

BACKGROUND: More and more MSers switch from natalizumab to fingolimod because of the risk of progressive multifocal leukoencephalopathy. The duration of the treatment holiday is still under debate referring to a possible recurrence of disease activity.

AIM OF THE STUDY: The aim of this study was to evaluate the prognostic value of natalizumab saturation on T cells for the recurrence of clinical and radiological disease activity.

METHODS: Cell surface-bound natalizumab saturation (in%) of CD8+ and CD4+ T cells from five MSers was determined before initiation of fingolimod by flow cytometry and related to clinical and MRI outcome during a 6-month follow-up.

RESULTS: In two MSers with either clinical or radiological disease activity, the natalizumab saturation on CD8+ and CD4+ T cells was <30%. In contrast, the remaining three patients with absence of disease activity had a median natalizumab saturation of 70% (range 59-79%) on CD4+ and 66% (range 52-68%) on CD8+ T cells.

CONCLUSIONS: The data of this pilot study indicate that clinical and radiological disease activity is closely linked to natalizumab saturation at the time point of switch. The determination of natalizumab saturation may be an essential tool to monitor cessation of natalizumab treatment.


  1. What if you are switching to Alem whilst being JCV (-) ?

    How long should the washout period be if your PML risk is negligible please?


    1. If you are JCV-ve your risk of PML is very low (<1 in 10,000); so if you have an unchanged MRI there will be virtually no risk at all. However, if you are JCV-ve and doing well on natalizumab you may not want to change your treatment.

    2. Thanks for the prompt reply.
      Much appreciated, as always.


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